Two-photon induced collagen cross-linking in bioartificial cardiac tissue

NASA Astrophysics Data System (ADS)

Kuetemeyer, Kai; Kensah, George; Heidrich, Marko; Meyer, Heiko; Martin, Ulrich; Gruh, Ina; Heisterkamp, Alexander

2011-08-01

Cardiac tissue engineering is a promising strategy for regenerative therapies to overcome the shortage of donor organs for transplantation. Besides contractile function, the stiffness of tissue engineered constructs is crucial to generate transplantable tissue surrogates with sufficient mechanical stability to withstand the high pressure present in the heart. Although several collagen cross-linking techniques have proven to be efficient in stabilizing biomaterials, they cannot be applied to cardiac tissue engineering, as cell death occurs in the treated area. Here, we present a novel method using femtosecond (fs) laser pulses to increase the stiffness of collagen-based tissue constructs without impairing cell viability. Raster scanning of the fs laser beam over riboflavin-treated tissue induced collagen cross-linking by two-photon photosensitized singlet oxygen production. One day post-irradiation, stress-strain measurements revealed increased tissue stiffness by around 40% being dependent on the fibroblast content in the tissue. At the same time, cells remained viable and fully functional as demonstrated by fluorescence imaging of cardiomyocyte mitochondrial activity and preservation of active contraction force. Our results indicate that two-photon induced collagen cross-linking has great potential for studying and improving artificially engineered tissue for regenerative therapies.

An estrogen receptor targeted ruthenium complex as a two-photon photodynamic therapy agent for breast cancer cells.

PubMed

Zhao, Xueze; Li, Mingle; Sun, Wen; Fan, Jiangli; Du, Jianjun; Peng, Xiaojun

2018-06-21

In this study, we reported a tamoxifen modified Ru(ii) polypyridyl complex (Ru-tmxf) as an estrogen receptor (ER) targeted photosensitizer. Ru-tmxf displays enhanced cellular uptake and PDT efficiency toward breast cancer cells with high ER expression due to the specific targeting of tamoxifen to ER and finally localizes in lysosomes. Moreover, Ru-tmxf can be activated by two-photon excitation, generating 1O2 to damage lysosomes and result in cell death.

Measurement of neutron dose equivalent outside and inside of the treatment vault of GRID therapy.

PubMed

Wang, Xudong; Charlton, Michael A; Esquivel, Carlos; Eng, Tony Y; Li, Ying; Papanikolaou, Nikos

2013-09-01

To evaluate the neutron and photon dose equivalent rates at the treatment vault entrance (Hn,D and HG), and to study the secondary radiation to the patient in GRID therapy. The radiation activation on the grid was studied. A Varian Clinac 23EX accelerator was working at 18 MV mode with a grid manufactured by .decimal, Inc. The Hn,D and HG were measured using an Andersson-Braun neutron REM meter, and a Geiger Müller counter. The radiation activation on the grid was measured after the irradiation with an ion chamber γ-ray survey meter. The secondary radiation dose equivalent to patient was evaluated by etched track detectors and OSL detectors on a RANDO(®) phantom. Within the measurement uncertainty, there is no significant difference between the Hn,D and HG with and without a grid. However, the neutron dose equivalent to the patient with the grid is, on average, 35.3% lower than that without the grid when using the same field size and the same amount of monitor unit. The photon dose equivalent to the patient with the grid is, on average, 44.9% lower. The measured average half-life of the radiation activation in the grid is 12.0 (± 0.9) min. The activation can be categorized into a fast decay component and a slow decay component with half-lives of 3.4 (± 1.6) min and 15.3 (± 4.0) min, respectively. There was no detectable radioactive contamination found on the surface of the grid through a wipe test. This work indicates that there is no significant change of the Hn,D and HG in GRID therapy, compared with a conventional external beam therapy. However, the neutron and scattered photon dose equivalent to the patient decrease dramatically with the grid and can be clinical irrelevant. Meanwhile, the users of a grid should be aware of the possible high dose to the radiation worker from the radiation activation on the surface of the grid. A delay in handling the grid after the beam delivery is suggested.

Pencil beam scanning proton therapy vs rotational arc radiation therapy: A treatment planning comparison for postoperative oropharyngeal cancer

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

Apinorasethkul, Ontida, E-mail: Ontida.a@gmail.com; Kirk, Maura; Teo, Kevin

Patients diagnosed with head and neck cancer are traditionally treated with photon radiotherapy. Proton therapy is currently being used clinically and may potentially reduce treatment-related toxicities by minimizing the dose to normal organs in the treatment of postoperative oropharyngeal cancer. The finite range of protons has the potential to significantly reduce normal tissue toxicity compared to photon radiotherapy. Seven patients were planned with both proton and photon modalities. The planning goal for both modalities was achieving the prescribed dose to 95% of the planning target volume (PTV). Dose-volume histograms were compared in which all cases met the target coverage goals.more » Mean doses were significantly lower in the proton plans for the oral cavity (1771 cGy photon vs 293 cGy proton, p < 0.001), contralateral parotid (1796 cGy photon vs 1358 proton, p < 0.001), and the contralateral submandibular gland (3608 cGy photon vs 3251 cGy proton, p = 0.03). Average total integral dose was 9.1% lower in proton plans. The significant dosimetric sparing seen with proton therapy may lead to reduced side effects such as pain, weight loss, taste changes, and dry mouth. Prospective comparisons of protons vs photons for disease control, toxicity, and patient-reported outcomes are therefore warranted and currently being pursued.« less

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

Development of dose delivery verification by PET imaging of photonuclear reactions following high energy photon therapy

NASA Astrophysics Data System (ADS)

Janek, S.; Svensson, R.; Jonsson, C.; Brahme, A.

2006-11-01

A method for dose delivery monitoring after high energy photon therapy has been investigated based on positron emission tomography (PET). The technique is based on the activation of body tissues by high energy bremsstrahlung beams, preferably with energies well above 20 MeV, resulting primarily in 11C and 15O but also 13N, all positron-emitting radionuclides produced by photoneutron reactions in the nuclei of 12C, 16O and 14N. A PMMA phantom and animal tissue, a frozen hind leg of a pig, were irradiated to 10 Gy and the induced positron activity distributions were measured off-line in a PET camera a couple of minutes after irradiation. The accelerator used was a Racetrack Microtron at the Karolinska University Hospital using 50 MV scanned photon beams. From photonuclear cross-section data integrated over the 50 MV photon fluence spectrum the predicted PET signal was calculated and compared with experimental measurements. Since measured PET images change with time post irradiation, as a result of the different decay times of the radionuclides, the signals from activated 12C, 16O and 14N within the irradiated volume could be separated from each other. Most information is obtained from the carbon and oxygen radionuclides which are the most abundant elements in soft tissue. The predicted and measured overall positron activities are almost equal (-3%) while the predicted activity originating from nitrogen is overestimated by almost a factor of two, possibly due to experimental noise. Based on the results obtained in this first feasibility study the great value of a combined radiotherapy-PET-CT unit is indicated in order to fully exploit the high activity signal from oxygen immediately after treatment and to avoid patient repositioning. With an RT-PET-CT unit a high signal could be collected even at a dose level of 2 Gy and the acquisition time for the PET could be reduced considerably. Real patient dose delivery verification by means of PET imaging seems to be applicable provided that biological transport processes such as capillary blood flow containing mobile 15O and 11C in the activated tissue volume can be accounted for.

In vivo neutron activation analysis of sodium and chlorine in tumor tissue after fast neutron therapy.

PubMed

Auberger, T; Koester, L; Knopf, K; Weissfloch, L

1996-01-01

In 12 patients with recurrences and metastases of different primaries (head and neck cancer, breast cancer, malignant melanoma, and osteosarcoma) who were treated with reactor fission neutrons the photon emission of irradiated tissue was measured after each radiotherapy fraction. Spectral analyses of the decay rates resulted in data for the exchange of sodium (Na) and chlorine (Cl) between the irradiated tissue and the body. About 60% of Na and Cl exchanged rapidly with a turnover half-life of 13 +/- 2 min. New defined mass exchange rates for Na and Cl amount to an average of 0.8 mval/min/kg of soft tissue. At the beginning of radiotherapy the turnover of the electrolytes in tissues with large tumor volumes was about twice that in tissues with small tumor volumes. Depending on the dose, neutron therapy led in all cases to variation in the metabolism. A maximum of Cl exchange and a minimum of Na exchange occurred after 10 Gy of neutrons (group of six previously untreated patients) or after 85 Gy (photon equivalent dose) of combined photon-neutron therapy. A significant increase in non-exchangeable fraction of Na from about 40 to 80% was observed in three tumors after a neutron dose of 10 Gy administered in five fractions correlated with a rapid reduction of tissue within 4 weeks after end of therapy. These results demonstrate for the first time the local response of the electrolyte metabolism to radiotherapy.

Concept for individualized patient allocation: ReCompare--remote comparison of particle and photon treatment plans.

PubMed

Lühr, Armin; Löck, Steffen; Roth, Klaus; Helmbrecht, Stephan; Jakobi, Annika; Petersen, Jørgen B; Just, Uwe; Krause, Mechthild; Enghardt, Wolfgang; Baumann, Michael

2014-02-18

Identifying those patients who have a higher chance to be cured with fewer side effects by particle beam therapy than by state-of-the-art photon therapy is essential to guarantee a fair and sufficient access to specialized radiotherapy. The individualized identification requires initiatives by particle as well as non-particle radiotherapy centers to form networks, to establish procedures for the decision process, and to implement means for the remote exchange of relevant patient information. In this work, we want to contribute a practical concept that addresses these requirements. We proposed a concept for individualized patient allocation to photon or particle beam therapy at a non-particle radiotherapy institution that bases on remote treatment plan comparison. We translated this concept into the web-based software tool ReCompare (REmote COMparison of PARticlE and photon treatment plans). We substantiated the feasibility of the proposed concept by demonstrating remote exchange of treatment plans between radiotherapy institutions and the direct comparison of photon and particle treatment plans in photon treatment planning systems. ReCompare worked with several tested standard treatment planning systems, ensured patient data protection, and integrated in the clinical workflow. Our concept supports non-particle radiotherapy institutions with the patient-specific treatment decision on the optimal irradiation modality by providing expertise from a particle therapy center. The software tool ReCompare may help to improve and standardize this personalized treatment decision. It will be available from our website when proton therapy is operational at our facility.

Antimicrobial Photodynamic Inactivation and Antitumor Photodynamic Therapy with Fullerenes

NASA Astrophysics Data System (ADS)

de Freitas, Lucas F.

2016-04-01

This book provides detailed and current information on using fullerenes (bucky-balls) in photodynamic therapy (PDT), one of the most actively studied applications of photonic science in healthcare. This will serve as a useful source for researchers working in photomedicine and nanomedicine, especially those who are investigating PDT for cancer treatment and infectious disease treatment. The book runs the gamut from an introduction to the history and chemistry of fullerenes and some basic photochemistry, to the application of fullerenes as photosensitizers for cancer and antimicrobial inactivation.

X-ray evidence of low-energy photon therapy for cervical lordosis restoration and radial head spur healing

NASA Astrophysics Data System (ADS)

Fitz-Ritson, Donald; Filonenko, Natalia; Salansky, Norman M.

1994-09-01

X rays were used for low energy photon therapy (LEPT) efficacy assessment for cervical lordosis restoration and radial head spur healing. Two cases, their evaluation, and treatment are discussed along with the follow-up results.

Incidence of Second Malignancies Among Patients Treated With Proton Versus Photon Radiation

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

Chung, Christine S., E-mail: chungc1@sutterhealth.org; Yock, Torunn I.; Nelson, Kerrie

2013-09-01

Purpose: Proton radiation, when compared with photon radiation, allows delivery of increased radiation dose to the tumor while decreasing dose to adjacent critical structures. Given the recent expansion of proton facilities in the United States, the long-term sequelae of proton therapy should be carefully assessed. The objective of this study was to compare the incidence of second cancers in patients treated with proton radiation with a population-based cohort of matched patients treated with photon radiation. Methods and Materials: We performed a retrospective cohort study of 558 patients treated with proton radiation from 1973 to 2001 at the Harvard Cyclotron inmore » Cambridge, MA and 558 matched patients treated with photon therapy in the Surveillance, Epidemiology, and End Results (SEER) Program cancer registry. Patients were matched by age at radiation treatment, sex, year of treatment, cancer histology, and site. The main outcome measure was the incidence of second malignancies after radiation. Results: We matched 558 proton patients with 558 photon patients from the Surveillance, Epidemiology, and End Results registry. The median duration of follow-up was 6.7 years (interquartile range, 7.4) and 6.0 years (interquartile range, 9.3) in the proton and photon cohorts, respectively. The median age at treatment was 59 years in each cohort. Second malignancies occurred in 29 proton patients (5.2%) and 42 photon patients (7.5%). After we adjusted for sex, age at treatment, primary site, and year of diagnosis, proton therapy was not associated with an increased risk of second malignancy (adjusted hazard ratio, 0.52 [95% confidence interval, 0.32-0.85]; P=.009). Conclusions: The use of proton radiation therapy was not associated with a significantly increased risk of secondary malignancies compared with photon therapy. Longer follow-up of these patients is needed to determine if there is a significant decrease in second malignancies. Given the limitations of the study, these results should be viewed as hypothesis generating.« less

Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy

PubMed Central

de Freitas, Lucas Freitas; Hamblin, Michael R

2016-01-01

Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infra-red region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT. PMID:28070154

Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy.

PubMed

de Freitas, Lucas Freitas; Hamblin, Michael R

2016-01-01

Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infra-red region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.

Characteristics of a heavy water photoneutron source in boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Danial, Salehi; Dariush, Sardari; M. Salehi, Jozani

2013-07-01

Bremsstrahlung photon beams produced by medical linear accelerators are currently the most commonly used method of radiation therapy for cancerous tumors. Photons with energies greater than 8-10 MeV potentially generate neutrons through photonuclear interactions in the accelerator's treatment head, patient's body, and treatment room ambient. Electrons impinging on a heavy target generate a cascade shower of bremsstrahlung photons, the energy spectrum of which shows an end point equal to the electron beam energy. By varying the target thickness, an optimum thickness exists for which, at the given electron energy, maximum photon flux is achievable. If a source of high-energy photons i.e. bremsstrahlung, is conveniently directed to a suitable D2O target, a novel approach for production of an acceptable flux of filterable photoneturons for boron neutron capture therapy (BNCT) application is possible. This study consists of two parts. 1. Comparison and assessment of deuterium photonuclear cross section data. 2. Evaluation of the heavy water photonuclear source.

Two-photon excitation of porphyrin-functionalized porous silicon nanoparticles for photodynamic therapy.

PubMed

Secret, Emilie; Maynadier, Marie; Gallud, Audrey; Chaix, Arnaud; Bouffard, Elise; Gary-Bobo, Magali; Marcotte, Nathalie; Mongin, Olivier; El Cheikh, Khaled; Hugues, Vincent; Auffan, Mélanie; Frochot, Céline; Morère, Alain; Maillard, Philippe; Blanchard-Desce, Mireille; Sailor, Michael J; Garcia, Marcel; Durand, Jean-Olivier; Cunin, Frédérique

2014-12-03

Porous silicon nanoparticles (pSiNPs) act as a sensitizer for the 2-photon excitation of a pendant porphyrin using NIR laser light, for imaging and photodynamic therapy. Mannose-functionalized pSiNPs can be vectorized to MCF-7 human breast cancer cells through a mannose receptor-mediated endocytosis mechanism to provide a 3-fold enhancement of the 2-photon PDT effect. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Proton therapy detector studies under the experience gained at the CATANA facility

NASA Astrophysics Data System (ADS)

Cuttone, G.; Cirrone, G. A. P.; Di Rosa, F.; Lojacono, P. A.; Lo Nigro, S.; Marino, C.; Mongelli, V.; Patti, I. V.; Pittera, S.; Raffaele, L.; Russo, G.; Sabini, M. G.; Salamone, V.; Valastro, L. M.

2007-10-01

Proton therapy represents the most promising radiotherapy technique for external tumor treatments. At Laboratori Nazionali del Sud of the Istituto Nazionale di Fisica Nucleare (INFN-LNS), Catania (I), a proton therapy facility is active since March 2002 and 140 patients, mainly affected by choroidal and iris melanoma, have been successfully treated. Proton beams are characterized by higher dose gradients and linear energy transfer with respect to the conventional photon and electron beams, commonly used in medical centers for radiotherapy.In this paper, we report the experience gained in the characterization of different dosimetric systems, studied and/or developed during the last ten years in our proton therapy facility.

Concept for individualized patient allocation: ReCompare—remote comparison of particle and photon treatment plans

PubMed Central

2014-01-01

Background Identifying those patients who have a higher chance to be cured with fewer side effects by particle beam therapy than by state-of-the-art photon therapy is essential to guarantee a fair and sufficient access to specialized radiotherapy. The individualized identification requires initiatives by particle as well as non-particle radiotherapy centers to form networks, to establish procedures for the decision process, and to implement means for the remote exchange of relevant patient information. In this work, we want to contribute a practical concept that addresses these requirements. Methods We proposed a concept for individualized patient allocation to photon or particle beam therapy at a non-particle radiotherapy institution that bases on remote treatment plan comparison. We translated this concept into the web-based software tool ReCompare (REmote COMparison of PARticlE and photon treatment plans). Results We substantiated the feasibility of the proposed concept by demonstrating remote exchange of treatment plans between radiotherapy institutions and the direct comparison of photon and particle treatment plans in photon treatment planning systems. ReCompare worked with several tested standard treatment planning systems, ensured patient data protection, and integrated in the clinical workflow. Conclusions Our concept supports non-particle radiotherapy institutions with the patient-specific treatment decision on the optimal irradiation modality by providing expertise from a particle therapy center. The software tool ReCompare may help to improve and standardize this personalized treatment decision. It will be available from our website when proton therapy is operational at our facility. PMID:24548333

High energy photons excited photodynamic cancer therapy in vitro

NASA Astrophysics Data System (ADS)

Guo, Yiping; Sheng, Shi; Zhang, Wei; Lun, Michael; Tsai, Shih-Ming; Chin, Wei-Chun; Hoglund, Roy; Li, Changqing

2018-02-01

Photodynamic therapy (PDT) is a noninvasive phototherapy method that has been clinically approved for many years. During this type of therapy, the photosensitizing agent will be excited by optical photons to generate reactive oxygen species which can kill nearby cancer cells. However, due to the strong optical scattering and absorption of tissue, optical photons can only penetrate tissues in few millimeters which result in the limited applications of PDT to superficial lesions like skin cancers. In this study, to overcome the penetration limitations, we used high-energy photons to excite photosensitizers directly by assuming that high-energy photons generate low-energy optical photons in tissues to excite photosensitizers. Cesium- 137 irradiator has been used as the high-energy photon source. A fiber pigtailed diode laser was used to validate the photosensitizer's efficacy. We used MPPa as the photosensitizer to treat A549 cancer cell line with different concentrations of drug (10μM/ ml, 5 μM/ml, 2.5 μM/ml, 1 μM/ml and 0 μM/ml). We have performed an irradiation experiment for different time durations of 30 min, 15 min, 7 min to 3 min, respectively, and we also compared different drug concentrations and different exposure durations. Our study not only proved the MPPa PDT method was effective, but also indicated that high-energy photons enhanced PDT could potentially overcome the penetration limitations thus making PDT feasible for deep tissue cancer.

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer

NASA Astrophysics Data System (ADS)

González, S. J.; Pozzi, E. C. C.; Monti Hughes, A.; Provenzano, L.; Koivunoro, H.; Carando, D. G.; Thorp, S. I.; Casal, M. R.; Bortolussi, S.; Trivillin, V. A.; Garabalino, M. A.; Curotto, P.; Heber, E. M.; Santa Cruz, G. A.; Kankaanranta, L.; Joensuu, H.; Schwint, A. E.

2017-10-01

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson’s correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer.

PubMed

González, S J; Pozzi, E C C; Monti Hughes, A; Provenzano, L; Koivunoro, H; Carando, D G; Thorp, S I; Casal, M R; Bortolussi, S; Trivillin, V A; Garabalino, M A; Curotto, P; Heber, E M; Santa Cruz, G A; Kankaanranta, L; Joensuu, H; Schwint, A E

2017-10-03

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson's correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.

Two-Photon-Excited Silica and Organosilica Nanoparticles for Spatiotemporal Cancer Treatment.

PubMed

Croissant, Jonas G; Zink, Jeffrey I; Raehm, Laurence; Durand, Jean-Olivier

2018-04-01

Coherent two-photon-excited (TPE) therapy in the near-infrared (NIR) provides safer cancer treatments than current therapies lacking spatial and temporal selectivities because it is characterized by a 3D spatial resolution of 1 µm 3 and very low scattering. In this review, the principle of TPE and its significance in combination with organosilica nanoparticles (NPs) are introduced and then studies involving the design of pioneering TPE-NIR organosilica nanomaterials are discussed for bioimaging, drug delivery, and photodynamic therapy. Organosilica nanoparticles and their rich and well-established chemistry, tunable composition, porosity, size, and morphology provide ideal platforms for minimal side-effect therapies via TPE-NIR. Mesoporous silica and organosilica nanoparticles endowed with high surface areas can be functionalized to carry hydrophobic and biologically unstable two-photon absorbers for drug delivery and diagnosis. Currently, most light-actuated clinical therapeutic applications with NPs involve photodynamic therapy by singlet oxygen generation, but low photosensitizing efficiencies, tumor resistance, and lack of spatial resolution limit their applicability. On the contrary, higher photosensitizing yields, versatile therapies, and a unique spatial resolution are available with engineered two-photon-sensitive organosilica particles that selectively impact tumors while healthy tissues remain untouched. Patients suffering pathologies such as retinoblastoma, breast, and skin cancers will greatly benefit from TPE-NIR ultrasensitive diagnosis and therapy. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

A review of dosimetric and toxicity modeling of proton versus photon craniospinal irradiation for pediatrics medulloblastoma.

PubMed

Ho, Evangeline S Q; Barrett, Sarah A; Mullaney, Laura M

2017-08-01

Craniospinal irradiation (CSI) is the standard radiation therapy treatment for medulloblastoma. Conventional CSI photon therapy (Photon-CSI) delivers significant dose to surrounding normal tissue (NT). Research into pediatric CSI with proton therapy (Proton-CSI) has increased, with the aim of exploiting the potential to reduce NT dose and associated post-treatment complications. This review aims to compare treatment outcomes of pediatric medulloblastoma patients between Proton- and Photon-CSI treatments. A search and review of studies published between 1990 and 2016 comparing pediatric (2-18 years) medulloblastoma Proton- and Photon-CSI in three aspects - normal organ sparing and target coverage; normal organ dysfunction and second malignancy risks - was completed. Fifteen studies were selected for review and the results were directly compared. Proton-CSI reported improved out-of-field organ sparing while target coverage improvements were inconsistent. Normal organ dysfunction risks were predicted to be lower following Proton-CSI. Secondary malignancy risks (SMRs) were generally lower with Proton-CSI based on several different risk models. Proton-CSI conferred better treatment outcomes than Photon-CSI for pediatric medulloblastoma patients. This review serves to compare the current literature in the absence of long-term data from prospective studies.

Platinum Acetylide Two-Photon Chromophores (Preprint)

DTIC Science & Technology

2007-04-01

nonlinear photonics,6-s microfabrication,9,10 fluorescence imaging, II and photodynamic therapy.12Instantaneous absorption of two lower energy photons...results in initiation of the same photophysical processes as one-photon absorption (lP A) of one high- energy photon. This is advantageous for two...reasons. The first is that because of the use of a lower energy photon a material will be guarded from ionization effects from multiphoton absorption in

TH-D-BRC-00: Educational Point Counter/Point: Has Photon RT Hit the Limits?

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

NONE

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive.more » This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.« less

Handling Density Conversion in TPS.

PubMed

Isobe, Tomonori; Mori, Yutaro; Takei, Hideyuki; Sato, Eisuke; Tadano, Kiichi; Kobayashi, Daisuke; Tomita, Tetsuya; Sakae, Takeji

2016-01-01

Conversion from CT value to density is essential to a radiation treatment planning system. Generally CT value is converted to the electron density in photon therapy. In the energy range of therapeutic photon, interactions between photons and materials are dominated with Compton scattering which the cross-section depends on the electron density. The dose distribution is obtained by calculating TERMA and kernel using electron density where TERMA is the energy transferred from primary photons and kernel is a volume considering spread electrons. Recently, a new method was introduced which uses the physical density. This method is expected to be faster and more accurate than that using the electron density. As for particle therapy, dose can be calculated with CT-to-stopping power conversion since the stopping power depends on the electron density. CT-to-stopping power conversion table is also called as CT-to-water-equivalent range and is an essential concept for the particle therapy.

A theoretical model for the production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

PubMed

Melville, G; Fan Liu, Sau; Allen, B J

2006-09-01

Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation on a small scale by bombarding Ra-226 with high-energy photons from a medical linear accelerator (linac) to produce Ra-225, which subsequently decays to Ac-225, which can be used as a generator to produce Bi-213 for use in 'targeted alpha therapy' for cancer. This paper examines the possibility of producing Ac-225 with a linac using an accurate theoretical model in which the bremsstrahlung photon spectrum at 18 MV linac electron energy is convoluted with the corresponding photonuclear cross sections of Ra-226. The total integrated yield can then be obtained and is compared with a computer simulation. This study shows that at 18 MV, the photonuclear reaction on Ra-226 can produce low activities of Ac-225 with a linac. However, a high power linac with high current, pulse length and frequency is needed to produce practical amounts of Ac-225 and a useful reduction of Ra-226.

Dose assessment for the fetus considering scattered and secondary radiation from photon and proton therapy when treating a brain tumor of the mother

NASA Astrophysics Data System (ADS)

Geng, Changran; Moteabbed, Maryam; Seco, Joao; Gao, Yiming; Xu, X. George; Ramos-Méndez, José; Faddegon, Bruce; Paganetti, Harald

2016-01-01

The goal of this work was to determine the scattered photon dose and secondary neutron dose and resulting risk for the sensitive fetus from photon and proton radiotherapy when treating a brain tumor during pregnancy. Anthropomorphic pregnancy phantoms with three stages (3-, 6-, 9-month) based on ICRP reference parameters were implemented in Monte Carlo platform TOPAS, to evaluate the scattered dose and secondary neutron dose and dose equivalent. To evaluate the dose equivalent, dose averaged quality factors were considered for neutrons. This study compared three treatment modalities: passive scattering and pencil beam scanning proton therapy (PPT and PBS) and 6-MV 3D conformal photon therapy. The results show that, for 3D conformal photon therapy, the scattered photon dose equivalent to the fetal body increases from 0.011 to 0.030 mSv per treatment Gy with increasing stage of gestation. For PBS, the neutron dose equivalent to the fetal body was significantly lower, i.e. increasing from 1.5  ×  10-3 to 2.5  ×  10-3 mSv per treatment Gy with increasing stage of gestation. For PPT, the neutron dose equivalent of the fetus decreases from 0.17 to 0.13 mSv per treatment Gy with the growing fetus. The ratios of dose equivalents to the fetus for a 52.2 Gy(RBE) course of radiation therapy to a typical CT scan of the mother’s head ranged from 3.4-4.4 for PBS, 30-41 for 3D conformal photon therapy and 180-500 for PPT, respectively. The attained dose to a fetus from the three modalities is far lower than the thresholds of malformation, severe mental retardation and lethal death. The childhood cancer excessive absolute risk was estimated using a linear no-threshold dose-response relationship. The risk would be 1.0 (95% CI: 0.6, 1.6) and 0.1 (95% CI:  -0.01, 0.52) in 105 for the 9-month fetus for PBS with a prescribed dose of 52.2 Gy(RBE). The increased risks for PPT and photon therapy are about two and one orders of magnitude larger than that for PBS, respectively. We can conclude that a pregnant woman with a brain tumor could be treated with pencil beam scanning with acceptable risks to the fetus.

Comparing the dosimetric impact of interfractional anatomical changes in photon, proton and carbon ion radiotherapy for pancreatic cancer patients

NASA Astrophysics Data System (ADS)

Houweling, Antonetta C.; Crama, Koen; Visser, Jorrit; Fukata, Kyohei; Rasch, Coen R. N.; Ohno, Tatsuya; Bel, Arjan; van der Horst, Astrid

2017-04-01

Radiotherapy using charged particles is characterized by a low dose to the surrounding healthy organs, while delivering a high dose to the tumor. However, interfractional anatomical changes can greatly affect the robustness of particle therapy. Therefore, we compared the dosimetric impact of interfractional anatomical changes (i.e. body contour differences and gastrointestinal gas volume changes) in photon, proton and carbon ion therapy for pancreatic cancer patients. In this retrospective planning study, photon, proton and carbon ion treatment plans were created for 9 patients. Fraction dose calculations were performed using daily cone-beam CT (CBCT) images. To this end, the planning CT was deformably registered to each CBCT; gastrointestinal gas volumes were delineated on the CBCTs and copied to the deformed CT. Fraction doses were accumulated rigidly. To compare planned and accumulated dose, dose-volume histogram (DVH) parameters of the planned and accumulated dose of the different radiotherapy modalities were determined for the internal gross tumor volume, internal clinical target volume (iCTV) and organs-at-risk (OARs; duodenum, stomach, kidneys, liver and spinal cord). Photon plans were highly robust against interfractional anatomical changes. The difference between the planned and accumulated DVH parameters for the photon plans was less than 0.5% for the target and OARs. In both proton and carbon ion therapy, however, coverage of the iCTV was considerably reduced for the accumulated dose compared with the planned dose. The near-minimum dose ({{D}98 % } ) of the iCTV reduced with 8% for proton therapy and with 10% for carbon ion therapy. The DVH parameters of the OARs differed less than 3% for both particle modalities. Fractionated radiotherapy using photons is highly robust against interfractional anatomical changes. In proton and carbon ion therapy, such changes can severely reduce the dose coverage of the target.

The in vivo activation of persistent nanophosphors for optical imaging of vascularization, tumours and grafted cells

NASA Astrophysics Data System (ADS)

Maldiney, Thomas; Bessière, Aurélie; Seguin, Johanne; Teston, Eliott; Sharma, Suchinder K.; Viana, Bruno; Bos, Adrie J. J.; Dorenbos, Pieter; Bessodes, Michel; Gourier, Didier; Scherman, Daniel; Richard, Cyrille

2014-04-01

Optical imaging for biological applications requires more sensitive tools. Near-infrared persistent luminescence nanoparticles enable highly sensitive in vivo optical detection and complete avoidance of tissue autofluorescence. However, the actual generation of persistent luminescence nanoparticles necessitates ex vivo activation before systemic administration, which prevents long-term imaging in living animals. Here, we introduce a new generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated in vivo through living tissues using highly penetrating low-energy red photons. Surface functionalization of this photonic probe can be adjusted to favour multiple biomedical applications such as tumour targeting. Notably, we show that cells can endocytose these nanoparticles in vitro and that, after intravenous injection, we can track labelled cells in vivo and follow their biodistribution by a simple whole animal optical detection, opening new perspectives for cell therapy research and for a variety of diagnosis applications.

Joint Estimation of Cardiac Toxicity and Recurrence Risks After Comprehensive Nodal Photon Versus Proton Therapy for Breast Cancer

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

Stick, Line B., E-mail: line.bjerregaard.stick@regionh.dk; Niels Bohr Institute, Faculty of Science, University of Copenhagen, Copenhagen; Yu, Jen

Purpose: The study aims to perform joint estimation of the risk of recurrence caused by inadequate radiation dose coverage of lymph node targets and the risk of cardiac toxicity caused by radiation exposure to the heart. Delivered photon plans are compared with realistic proton plans, thereby providing evidence-based estimates of the heterogeneity of treatment effects in consecutive cases for the 2 radiation treatment modalities. Methods and Materials: Forty-one patients referred for postlumpectomy comprehensive nodal photon irradiation for left-sided breast cancer were included. Comparative proton plans were optimized by a spot scanning technique with single-field optimization from 2 en face beams.more » Cardiotoxicity risk was estimated with the model of Darby et al, and risk of recurrence following a compromise of lymph node coverage was estimated by a linear dose-response model fitted to the recurrence data from the recently published EORTC (European Organisation for Research and Treatment of Cancer) 22922/10925 and NCIC-CTG (National Cancer Institute of Canada Clinical Trials Group) MA.20 randomized controlled trials. Results: Excess absolute risk of cardiac morbidity was small with photon therapy at an attained age of 80 years, with median values of 1.0% (range, 0.2%-2.9%) and 0.5% (range, 0.03%-1.0%) with and without cardiac risk factors, respectively, but even lower with proton therapy (0.13% [range, 0.02%-0.5%] and 0.06% [range, 0.004%-0.3%], respectively). The median estimated excess absolute risk of breast cancer recurrence after 10 years was 0.10% (range, 0.0%-0.9%) with photons and 0.02% (range, 0.0%-0.07%) with protons. The association between age of the patient and benefit from proton therapy was weak, almost non-existing (Spearman rank correlations of −0.15 and −0.30 with and without cardiac risk factors, respectively). Conclusions: Modern photon therapy yields limited risk of cardiac toxicity in most patients, but proton therapy can reduce the predicted risk of cardiac toxicity by up to 2.9% and the risk of breast cancer recurrence by 0.9% in individual patients. Predicted benefit correlates weakly with age. Combined assessment of the risk from cardiac exposure and inadequate target coverage is desirable for rational consideration of competing photon and proton therapy plans.« less

Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

NASA Astrophysics Data System (ADS)

Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan

2015-08-01

Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL) and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

Dynamic PET/CT measurements of induced positron activity in a prostate cancer patient after 50-MV photon radiation therapy.

PubMed

Janek Strååt, Sara; Jacobsson, Hans; Noz, Marilyn E; Andreassen, Björn; Näslund, Ingemar; Jonsson, Cathrine

2013-01-23

The purpose of this work was to reveal the research interest value of positron emission tomography (PET) imaging in visualizing the induced tissue activity post high-energy photon radiation treatment. More specifically, the focus was on the possibility of retrieving data such as tissue composition and physical half-lives from dynamic PET acquisitions, as positron-emitting radionuclides such as 15O, 11C, and 13N are produced in vivo during radiation treatment with high-energy photons (>15 MeV). The type, amount, and distribution of induced positron-emitting radionuclides depend on the irradiated tissue cross section, the photon spectrum, and the possible perfusion-driven washout. A 62-year-old man diagnosed with prostate cancer was referred for palliative radiation treatment of the pelvis minor. A total dose of 8 Gy was given using high-energy photon beams (50 MV) with a racetrack microtron, and 7 min after the end of irradiation, the patient was positioned in a PET/computed tomography (CT) camera, and a list-mode acquisition was performed for 30 min. Two volumes of interests (VOIs) were positioned on the dynamic PET/CT images, one in the urinary bladder and the other in the subcutaneous fat. Analysis of the measured relative count rate was performed in order to compute the tissue compositions and physical half-lives in the two regions. Dynamic analysis from the two VOIs showed that the decay constants of activated oxygen and carbon could be deduced. Calculation of tissue composition from analyzing the VOI containing subcutaneous fat only moderately agreed with that of the tabulated International Commission on Radiation Units & Measurements (ICRU) data of the adipose tissue. However, the same analysis for the bladder showed a good agreement with that of the tabulated ICRU data. PET can be used in visualizing the induced activity post high-energy photon radiation treatment. Despite the very low count rate in this specific application, wherein 7 min after treatment was about 5% of that of a standard 18F-FDG PET scan, the distribution of activated tissue elements (15O and 11C) could be calculated from the dynamic PET data. One possible future application of this method could possibly be to measure and determine the tumor tissue composition in order to identify any hypoxic or necrotic region, which is information that can be used in the ongoing therapy planning process. The official name of the trial committee of this study is 'Regionala etikprövningsnämnden i Stockholm' (FE 289, Stockholm, SE-17177, Sweden). The unique identifying number is 2011/1789-31/2.

6.3 MeV fast neutrons in the treatment of patients with locally advanced and locally recurrent breast cancer

NASA Astrophysics Data System (ADS)

Velikaya, V. V.; Musabaeva, L. I.; Lisin, V. A.; Startseva, Zh. A.

2016-08-01

The study included 135 breast cancer patients (70 patients with locally recurrent breast cancer and 65 patients with locally advanced breast cancer with unfavorable prognostic factors) who received the neutron therapy alone or in combination with the photon therapy. The neutron therapy was shown to be effective in multimodality treatment of patients with locally advanced and locally recurrent breast cancer. The 8-year survival rate in patients without repeated breast cancer recurrence was 87.6 ± 8.7% after the neutron and neutron-photon therapy and 54.3 ± 9.2% after the electron beam therapy.

6.3 MeV fast neutrons in the treatment of patients with locally advanced and locally recurrent breast cancer

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

Velikaya, V. V., E-mail: viktoria.v.v@inbox.ru; Startseva, Zh. A., E-mail: zhanna.alex@rambler.ru; National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk, 634050

The study included 135 breast cancer patients (70 patients with locally recurrent breast cancer and 65 patients with locally advanced breast cancer with unfavorable prognostic factors) who received the neutron therapy alone or in combination with the photon therapy. The neutron therapy was shown to be effective in multimodality treatment of patients with locally advanced and locally recurrent breast cancer. The 8-year survival rate in patients without repeated breast cancer recurrence was 87.6 ± 8.7% after the neutron and neutron-photon therapy and 54.3 ± 9.2% after the electron beam therapy.

LASERS IN MEDICINE: Two-photon excitation of aluminium phthalocyanines

NASA Astrophysics Data System (ADS)

Meshalkin, Yu P.; Alfimov, E. E.; Vasil'ev, N. E.; Denisov, A. N.; Makukha, V. K.; Ogirenko, A. P.

1999-12-01

A demonstration is given of the feasibility of two-photon excitation of aluminium phthalocyanine and of the pharmaceutical preparation 'Fotosens', used in photodynamic therapy. The excitation source was an Nd:YAG laser emitting at the 1064 nm wavelength. The spectra of the two-photon-excited luminescence were obtained and the two-photon absorption cross sections were determined.

Evaluation of dead-time corrections for post-radionuclide-therapy (177)Lu quantitative imaging with low-energy high-resolution collimators.

PubMed

Celler, Anna; Piwowarska-Bilska, Hanna; Shcherbinin, Sergey; Uribe, Carlos; Mikolajczak, Renata; Birkenfeld, Bozena

2014-01-01

Dead-time (DT) effects rarely cause problems in diagnostic single-photon emission computed tomography (SPECT) studies; however, in post-radionuclide-therapy imaging, DT can be substantial. Therefore, corrections may be necessary if quantitative images are used in image-based dosimetry or for evaluation of therapy outcomes. This task is particularly challenging if low-energy collimators are used. Our goal was to design a simple method to determine the dead-time correction factor (DTCF) without the need for phantom experiments and complex calculations. Planar and SPECT/CT scans of a water phantom containing a 70 ml bottle filled with lutetium-177 (Lu) were acquired over 60 days. Two small Lu markers were used in all scans. The DTCF based on the ratio of observed to true count rates measured over the entire spectrum and using photopeak primary photons only was estimated for phantom (DT present) and marker (no DT) scans. In addition, variations in counts in SPECT projections (potentially caused by varying bremsstrahlung and scatter) were investigated. For count rates that were about two-fold higher than typically seen in post-therapy Lu scans, the maximum DTCF reached a level of about 17%. The DTCF values determined directly from the phantom experiments using the total energy spectrum and photopeak counts only were equal to 13 and 16%, respectively. They were closely matched by those from the proposed marker-based method, which uses only two energy windows and measures photopeak primary photons (15-17%). A simple, marker-based method allowing for determination of the DTCF in high-activity Lu imaging studies has been proposed and validated using phantom experiments.

Predicting the sensitivity to ion therapy based on the response to photon irradiation--experimental evidence and mathematical modelling.

PubMed

Mohanty, Chitralekha; Zielinska-Chomej, Katarzyna; Edgren, Margareta; Hirayama, Ryoichi; Murakami, Takeshi; Lind, Bengt; Toma-Dasu, Iuliana

2014-06-01

The use of ion radiation therapy is growing due to the continuously increasing positive clinical experience obtained. Therefore, there is a high interest in radio-biological experiments comparing the relative efficiency in cell killing of ions and photons as photons are currently the main radiation modality used for cancer treatment. This comparison is particularly important since the treatment planning systems (TPSs) used at the main ion therapy Centers make use of parameters describing the cellular response to photons, respectively ions, determined in vitro. It was, therefore, the aim of this article to compare the effects of high linear energy transfer (LET) ion radiation with low LET photons and determine whether the cellular response to low LET could predict the response to high LET irradiation. Clonogenic cell survival data of five tumor cell lines irradiated with different ion beams of similar, clinically-relevant, LET were studied in relation to response to low LET photons. Two mathematical models were used to fit the data, the repairable-conditionally repairable damage (RCR) model and the linear quadratic (LQ) model. The results indicate that the relative biological efficiency of the high LET radiation assessed with the RCR model could be predicted based only on the response to the low LET irradiation. The particular features of the RCR model indicate that tumor cells showing a large capacity for repairing the damage will have the larger benefit from radiation therapy with ion beams. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

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.

Volumetric response of intracranial meningioma after photon or particle irradiation.

PubMed

Mozes, Petra; Dittmar, Jan Oliver; Habermehl, Daniel; Tonndorf-Martini, Eric; Hideghety, Katalin; Dittmar, Anne; Debus, Jürgen; Combs, Stephanie E

2017-03-01

Meningiomas are usually slow growing, well circumscribed intracranial tumors. In symptom-free cases observation with close follow-up imaging could be performed. Symptomatic meningiomas could be surgically removed and/or treated with radiotherapy. The study aimed to evaluate the volumetric response of intracranial meningiomas at different time points after photon, proton, and a mixed photon and carbon ion boost irradiation. In Group A 38 patients received proton therapy (median dose: 56 GyE in 1.8-2 GyE daily fractions) or a mixed photon/carbon ion therapy (50 Gy in 2 Gy daily fractions with intensity modulated radiotherapy (IMRT) and 18 GyE in 3 GyE daily dose carbon ion boost). Thirty-nine patients (Group B) were treated by photon therapy with IMRT or fractionated stereotactic radiotherapy technique (median dose: 56 Gy in 1.8-2 Gy daily fractions). The delineation of the tumor volume was based on the initial, one- and two-year follow-up magnetic resonance imaging and these volumes were compared to evaluate the volumetric tumor response. Significant tumor volume shrinkage was detected at one- and at two-year follow-up both after irradiation by particles and by photons. No significant difference in tumor volume change was observed between photon, proton or combined photon plus carbon ion boost treated patients. WHO grade and gender appear to be determining factors for tumor volume shrinkage. Significant volumetric shrinkage of meningiomas could be observed independently of the applied radiation modality. Long-term follow-up is recommended to evaluate further dynamic of size reduction and its correlation with outcome data.

Evaluation of a GEM and CAT-based detector for radiation therapy beam monitoring

NASA Astrophysics Data System (ADS)

Brahme, A.; Danielsson, M.; Iacobaeus, C.; Ostling, J.; Peskov, V.; Wallmark, M.

2000-11-01

We are developing a radiation therapy beam monitor for the Karolinska Institute. This monitor will consist of two consecutive detectors confined in one gas chamber: a "keV-photon detector", which will allow diagnostic quality visualization of the patient, and a "MeV-photon detector", that will measure the absolute intensity of the therapy beam and its position with respect to the patient. Both detectors are based on highly radiation resistant gas and solid photon to electron converters, combined with GEMs and a CAT as amplification structures. We have performed systematic studies of the high-rate characteristics of the GEM and the CAT, as well as tested the electron transfer through these electron multipliers and various types of converters. The tests show that the GEM and the CAT satisfy all requirements for the beam monitoring system. As a result of these studies we successfully developed and tested a full section of the beam monitor equipped with a MeV-photon converter placed between the GEM and the CAT.

Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons.

PubMed

Lin, Yuting; Paganetti, Harald; McMahon, Stephen J; Schuemann, Jan

2015-10-01

The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photon beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor.

Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons

PubMed Central

Lin, Yuting; Paganetti, Harald; McMahon, Stephen J.; Schuemann, Jan

2015-01-01

Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photon beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. Conclusions: GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor. PMID:26429263

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.

TH-D-BRC-01: Panel Member

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

Aydogan, B.

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive.more » This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.« less

TH-D-BRC-02: Panel Member

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

Hahn, S.

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive.more » This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.« less

TH-D-BRC-04: Panel Member

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

Yu, C.

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive.more » This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.« less

TH-D-BRC-03: Panel Member

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

Paganetti, H.

Interest in proton therapy has increased dramatically in the past couple of years, especially in the United States. There certainly is an important place for proton therapy in the arsenal of cancer treatments. Its dosimetric advantage and potential for low toxicity makes it the perfect partner for photons and other cancer treatment modalities. Often there is a belief that the new technology ought to be better but many believe that they should be widely adopted in the clinic only after evidence has shown that they are at least as safe and efficacious as existing technologies, which are often less expensive.more » This is the case for proton radiotherapy. This session being both educational and debate will provide a good review of basics and technological advancement as well as a comprehensive clinical update for both proton and photon therapy. Future technology developments and how they will impact the potential dosimetric advantage of proton therapy will be discussed. Particularly the debate will focus on whether these developments will close or widen the gap between photon and proton therapy. Learning Objectives: To review challenges, limitations, and recent and future developments in proton therapy. To review challenges, limitations, recent and future developments in photon radiotherapy. To review current clinical trials and challenging clinical cases. C. Yu, No company or organization that my presentation mentions provided me with financial support. I am the Founder and CEO of Xcision Medical Systems, LLC. However, my presentation will not mention any product or technology developed by Xcision.« less

Socioeconomic factors affect the selection of proton radiation therapy for children.

PubMed

Shen, Colette J; Hu, Chen; Ladra, Matthew M; Narang, Amol K; Pollack, Craig E; Terezakis, Stephanie A

2017-10-15

Proton radiotherapy remains a limited resource despite its clear potential for reducing radiation doses to normal tissues and late effects in children in comparison with photon therapy. This study examined the impact of race and socioeconomic factors on the use of proton therapy in children with solid malignancies. This study evaluated 12,101 children (age ≤ 21 years) in the National Cancer Data Base who had been diagnosed with a solid malignancy between 2004 and 2013 and had received photon- or proton-based radiotherapy. Logistic regression analysis was used to evaluate patient, tumor, and socioeconomic variables affecting treatment with proton radiotherapy versus photon radiotherapy. Eight percent of the patients in the entire cohort received proton radiotherapy, and this proportion increased between 2004 (1.7%) and 2013 (17.5%). Proton therapy was more frequently used in younger patients (age ≤ 10 years; odds ratio [OR], 1.9; 95% confidence interval [CI], 1.6-2.2) and in patients with bone/joint primaries and ependymoma, medulloblastoma, and rhabdomyosarcoma histologies (P < .05). Patients with metastatic disease were less likely to receive proton therapy (OR, 0.4; 95% CI, 0.3-0.6). Patients with private/managed care were more likely than patients with Medicaid or no insurance to receive proton therapy (P < .0001). A higher median household income and educational attainment were also associated with increased proton use (P < .001). Patients treated with proton therapy versus photon therapy were more likely to travel more than 200 miles (13% vs 5%; P < .0001). Socioeconomic factors affect the use of proton radiotherapy in children. Whether this disparity is related to differences in the referral patterns, the knowledge of treatment modalities, or the ability to travel for therapy needs to be further clarified. Improving access to proton therapy in underserved pediatric populations is essential. Cancer 2017;123:4048-56. © 2017 American Cancer Society. © 2017 American Cancer Society.

Gold nanoparticle induced vasculature damage in radiotherapy: Comparing protons, megavoltage photons, and kilovoltage photons

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

Lin, Yuting, E-mail: yutingl188@gmail.com; Paganetti, Harald; Schuemann, Jan

2015-10-15

Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) photon, and kilovoltage (kV) photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV photonmore » beam, and two kV photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp photon source, 1% for the 6 MV photon source, and 0.1% for the proton beam. For kV photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp photon source, 4% for the 6 MV photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. Conclusions: GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor.« less

Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron

NASA Astrophysics Data System (ADS)

Musabaeva, L. I.; Startseva, Zh. A.; Gribova, O. V.; Velikaya, V. V.; Lisin, V. A.

2016-08-01

The analysis of clinical use of neutron therapy with 6 MeV fast neutrons compared to conventional radiation therapy was carried out. The experience of using neutron and mixed neutron and photon therapy in patients with different radio-resistant malignant tumors shows the necessity of further studies and development of the novel approaches to densely-ionizing radiation. The results of dosimetry and radiobiological studies have been the basis for planning clinical programs for neutron therapy. Clinical trials over the past 30 years have shown that neutron therapy successfully destroys radio-resistant cancers, including salivary gland tumors, adenoidcystic carcinoma, inoperable sarcomas, locally advanced head and neck tumors, and locally advanced prostate cancer. Radiation therapy with 6.3 MeV fast neutrons used alone and in combination with photon therapy resulted in improved long-term treatment outcomes in patients with radio-resistant malignant tumors.

Proton Therapy for Head and Neck Cancer.

PubMed

Kim, Joseph K; Leeman, Jonathan E; Riaz, Nadeem; McBride, Sean; Tsai, Chiaojung Jillian; Lee, Nancy Y

2018-05-09

The application of proton beam radiation therapy in the treatment of head and neck cancer has grown tremendously in the past few years. Globally, widespread interest in proton beam therapy has led to multiple research efforts regarding its therapeutic value and cost-effectiveness. The current standard of care using modern photon radiation technology has demonstrated excellent treatment outcomes, yet there are some situations where disease control remains suboptimal with the potential for detrimental acute and chronic toxicities. Due to the advantageous physical properties of the proton beam, proton beam therapy may be superior to photon therapy in some patient subsets for both disease control and patient quality of life. As enthusiasm and excitement for proton beam therapy continue to increase, clinical research and widespread adoption will elucidate the true value of proton beam therapy and give a greater understanding of the full risks and benefits of proton therapy in head and neck cancer.

Targeted two-photon photodynamic therapy for the treatment of subcutaneous tumors

NASA Astrophysics Data System (ADS)

Spangler, Charles W.; Starkey, Jean R.; Meng, Fanqing; Gong, Aijun; Drobizhev, Mikhail; Rebane, Aleksander; Moss, B.

2005-04-01

Photodynamic therapy (PDT) has developed into a mature technology over the past several years, and is currently being exploited for the treatment of a variety of cancerous tumors, and more recently for age-related wet macular degeneration of the eye. However, there are still some unresolved problems with PDT that are retarding a more general acceptance in clinical settings, and thus, for the most part, the treatment of most cancerous rumors still involves some combination of invasive surgery, chemotherapy and radiation treatment, particularly subcutaneous tumors. Currently approved PDT agents are activated in the Visible portion of the spectrum below 700 nm, Laser light in this spectral region cannot penetrate the skin more than a few millimeters, and it would be more desirable if PDT could be initiated deep in the Near-infrared (NIR) in the tissue transparency window (700-1000 nm). MPA Technologies, Inc. and Rasiris, Inc. have been co-developing new porphyrin PDT designed to have greatly enhanced intrinsic two-photon cross-sections (>800 GM units) whose two-photon absorption maxima lie deep in the tissue transparency window (ca. 780-850 nm), and have solubility characteristics that would allow for direct IV injection into animal models. Classical PDT also suffers from the lengthy time necessary for accumulation at the tumor site, a relative lack of discrimination between healthy and diseased tissue, particularly at the tumor margins, and difficulty in clearing from the system in a reasonable amount of time post-PDT. We have recently discovered a new design paradigm for the delivery of our two-photon activated PDT agents by incorporating the porphyrins into a triad ensemble that includes a small molecule targeting agent that directs the triad to over-expressed tumor receptor sites, and a NIR one-photon imaging agent that allows the tracking of the triad in terms of accumulation and clearance rates. We are currently using these new two-photon PDT triads in efficacy studies with two breast cancer cell lines, both in vitro and in vivo. Both of these cell lines have been transfected with luciferase genes that allow implanted tumor growth and PDT efficacy to be monitored in living mouse models over time by following the rise and decay of the bioluminescence signals.

Photon activated therapy (PAT) using monochromatic Synchrotron x-rays and iron oxide nanoparticles in a mouse tumor model: feasibility study of PAT for the treatment of superficial malignancy

PubMed Central

2012-01-01

Background X-rays are known to interact with metallic nanoparticles, producing photoelectric species as radiosensitizing effects, and have been exploited in vivo mainly with gold nanoparticles. The purpose of this study was to investigate the potential of sensitizing effect of iron oxide nanoparticles for photon activated therapy. Methods X-rays photon activated therapy (PAT) was studied by treating CT26 tumor cells and CT26 tumor-bearing mice loaded with 13-nm diameter FeO NP, and irradiating them at 7.1 keV near the Fe K-edge using synchrotron x-rays radiation. Survival of cells was determined by MTT assay, and tumor regression assay was performed for in vivo model experiment. The results of PAT treated groups were compared with x-rays alone control groups. Results A more significant reduction in viability and damage was observed in the FeO NP-treated irradiated cells, compared to the radiation alone group (p < 0.04). Injection of FeO NP (100 mg/kg) 30 min prior to irradiation elevated the tumor concentration of magnetite to 40 μg of Fe/g tissue, with a tumor-to-muscle ratio of 17.4. The group receiving FeO NP and radiation of 10 Gy showed 80% complete tumor regression (CTR) after 15–35 days and relapse-free survival for up to 6 months, compared to the control group, which showed growth retardation, resulting in 80% fatality. The group receiving radiation of 40 Gy showed 100% CTR in all cases irrespective of the presence of FeO NP, but CTR was achieved earlier in the PAT-treated group compared with the radiation alone group. Conclusions An iron oxide nanoparticle enhanced therapeutic effect with relatively low tissue concentration of iron and 10 Gy of monochromatic X-rays. Since 7.1 keV X-rays is attenuated very sharply in the tissue, FeO NP-PAT may have promise as a potent treatment option for superficial malignancies in the skin, like chest wall recurrence of breast cancer. PMID:23111059

SU-F-T-376: The Efficiency of Calculating Photonuclear Reaction On High-Energy Photon Therapy by Monte Carlo Method

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

Hirayama, S; Fujibuchi, T

Purpose: Secondary-neutrons having harmful influences to a human body are generated by photonuclear reaction on high-energy photon therapy. Their characteristics are not known in detail since the calculation to evaluate them takes very long time. PHITS(Particle and Heavy Ion Transport code System) Monte Carlo code since versions 2.80 has the new parameter “pnimul” raising the probability of occurring photonuclear reaction forcibly to make the efficiency of calculation. We investigated the optimum value of “pnimul” on high-energy photon therapy. Methods: The geometry of accelerator head based on the specification of a Varian Clinac 21EX was used for PHITS ver. 2.80. Themore » phantom (30 cm * 30 cm * 30 cm) filled the composition defined by ICRU(International Commission on Radiation Units) was placed at source-surface distance 100 cm. We calculated the neutron energy spectra in the surface of ICRU phantom with “pnimal” setting 1, 10, 100, 1000, 10000 and compared the total calculation time and the behavior of photon using PDD(Percentage Depth Dose) and OCR(Off-Center Ratio). Next, the cutoff energy of photon, electron and positron were investigated for the calculation efficiency with 4, 5, 6 and 7 MeV. Results: The calculation total time until the errors of neutron fluence become within 1% decreased as increasing “pnimul”. PDD and OCR showed no differences by the parameter. The calculation time setting the cutoff energy like 4, 5, 6 and 7 MeV decreased as increasing the cutoff energy. However, the errors of photon become within 1% did not decrease by the cutoff energy. Conclusion: The optimum values of “pnimul” and the cutoff energy were investigated on high-energy photon therapy. It is suggest that using the optimum “pnimul” makes the calculation efficiency. The study of the cutoff energy need more investigation.« less

In vivo and phantom measurements of the secondary photon and neutron doses for prostate patients undergoing 18 MV IMRT.

PubMed

Reft, Chester S; Runkel-Muller, Renate; Myrianthopoulos, Leon

2006-10-01

For intensity modulated radiation therapy (IMRT) treatments 6 MV photons are typically used, however, for deep seated tumors in the pelvic region, higher photon energies are increasingly being employed. IMRT treatments require more monitor units (MU) to deliver the same dose as conformal treatments, causing increased secondary radiation to tissues outside the treated area from leakage and scatter, as well as a possible increase in the neutron dose from photon interactions in the machine head. Here we provide in vivo patient and phantom measurements of the secondary out-of-field photon radiation and the neutron dose equivalent for 18 MV IMRT treatments. The patients were treated for prostate cancer with 18 MV IMRT at institutions using different therapy machines and treatment planning systems. Phantom exposures at the different facilities were used to compare the secondary photon and neutron dose equivalent between typical IMRT delivered treatment plans with a six field three-dimensional conformal radiotherapy (3DCRT) plan. For the in vivo measurements LiF thermoluminescent detectors (TLDs) and Al2O3 detectors using optically stimulated radiation were used to obtain the photon dose and CR-39 track etch detectors were used to obtain the neutron dose equivalent. For the phantom measurements a Bonner sphere (25.4 cm diameter) containing two types of TLDs (TLD-600 and TLD-700) having different thermal neutron sensitivities were used to obtain the out-of-field neutron dose equivalent. Our results showed that for patients treated with 18 MV IMRT the photon dose equivalent is greater than the neutron dose equivalent measured outside the treatment field and the neutron dose equivalent normalized to the prescription dose varied from 2 to 6 mSv/Gy among the therapy machines. The Bonner sphere results showed that the ratio of neutron equivalent doses for the 18 MV IMRT and 3DCRT prostate treatments scaled as the ratio of delivered MUs. We also observed differences in the measured neutron dose equivalent among the three therapy machines for both the in vivo and phantom exposures.

A novel flurophore-cyano-carboxylic-Ag microhybrid: Enhanced two photon absorption for two-photon photothermal therapy of HeLa cancer cells by targeting mitochondria.

PubMed

Kong, Lin; Yang, Li; Xin, Chen-Qi; Zhu, Shu-Juan; Zhang, Hui-Hui; Zhang, Ming-Zhu; Yang, Jia-Xiang; Li, Lin; Zhou, Hong-Ping; Tian, Yu-Peng

2018-06-15

In this study, a novel two-photon photothermal therapy (TP-PTT) agent based on an organic-metal microhybrid with surface Plasmon resonance (SPR) enhanced two-photon absorption (TPA) characteristic was designed and synthesized using a fluorescent cyano-carboxylic derivative 2-cyano-3-(9-ethyl-9H-carbazol-3-yl) -acrylic acid (abbreviated as CECZA) and silver nanoparticles through self-assembly process induced by the interfacial coordination interactions between the O/N atom of CECZA and Ag + ion at the surface of Ag nanoparticles. The coordination interactions caused electron transfer from the Ag nanoparticles to CECZA molecules at the excited state, resulting in a decreased fluorescence quantum yield. The interfacial coordination interactions also enhanced the nonlinear optical properties, including 13 times increase in the TPA cross-section (δ). The decreased fluorescence quantum yield and increased two photon absorption caused by the SPR effect led excellent two-photon photothermal conversion, which was beneficial for the TP-PTT effect on HeLa cancer cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Accuracy and Precision of Radioactivity Quantification in Nuclear Medicine Images

PubMed Central

Frey, Eric C.; Humm, John L.; Ljungberg, Michael

2012-01-01

The ability to reliably quantify activity in nuclear medicine has a number of increasingly important applications. Dosimetry for targeted therapy treatment planning or for approval of new imaging agents requires accurate estimation of the activity in organs, tumors, or voxels at several imaging time points. Another important application is the use of quantitative metrics derived from images, such as the standard uptake value commonly used in positron emission tomography (PET), to diagnose and follow treatment of tumors. These measures require quantification of organ or tumor activities in nuclear medicine images. However, there are a number of physical, patient, and technical factors that limit the quantitative reliability of nuclear medicine images. There have been a large number of improvements in instrumentation, including the development of hybrid single-photon emission computed tomography/computed tomography and PET/computed tomography systems, and reconstruction methods, including the use of statistical iterative reconstruction methods, which have substantially improved the ability to obtain reliable quantitative information from planar, single-photon emission computed tomography, and PET images. PMID:22475429

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

Radiation dose enhancement in skin therapy with nanoparticle addition: A Monte Carlo study on kilovoltage photon and megavoltage electron beams

PubMed Central

Zheng, Xiao J; Chow, James C L

2017-01-01

AIM To investigated the dose enhancement due to the incorporation of nanoparticles in skin therapy using the kilovoltage (kV) photon and megavoltage (MV) electron beams. Monte Carlo simulations were used to predict the dose enhancement when different types and concentrations of nanoparticles were added to skin target layers of varying thickness. METHODS Clinical kV photon beams (105 and 220 kVp) and MV electron beams (4 and 6 MeV), produced by a Gulmay D3225 orthovoltage unit and a Varian 21 EX linear accelerator, were simulated using the EGSnrc Monte Carlo code. Doses at skin target layers with thicknesses ranging from 0.5 to 5 mm for the photon beams and 0.5 to 10 mm for the electron beams were determined. The skin target layer was added with the Au, Pt, I, Ag and Fe2O3 nanoparticles with concentrations ranging from 3 to 40 mg/mL. The dose enhancement ratio (DER), defined as the dose at the target layer with nanoparticle addition divided by the dose at the layer without nanoparticle addition, was calculated for each nanoparticle type, nanoparticle concentration and target layer thickness. RESULTS It was found that among all nanoparticles, Au had the highest DER (5.2-6.3) when irradiated with kV photon beams. Dependence of the DER on the target layer thickness was not significant for the 220 kVp photon beam but it was for 105 kVp beam for Au nanoparticle concentrations higher than 18 mg/mL. For other nanoparticles, the DER was dependent on the atomic number of the nanoparticle and energy spectrum of the photon beams. All nanoparticles showed an increase of DER with nanoparticle concentration during the photon beam irradiations regardless of thickness. For electron beams, the Au nanoparticles were found to have the highest DER (1.01-1.08) when the beam energy was equal to 4 MeV, but this was drastically lower than the DER values found using photon beams. The DER was also found affected by the depth of maximum dose of the electron beam and target thickness. For other nanoparticles with lower atomic number, DERs in the range of 0.99-1.02 were found using the 4 and 6 MeV electron beams. CONCLUSION In nanoparticle-enhanced skin therapy, Au nanoparticle addition can achieve the highest dose enhancement with 105 kVp photon beams. Electron beams, while popular for skin therapy, did not produce as high dose enhancements as kV photon beams. Additionally, the DER is dependent on nanoparticle type, nanoparticle concentration, skin target thickness and energies of the photon and electron beams. PMID:28298966

Iodine-131 Therapy and Lacrimal Drainage System Toxicity: Nasal Localization Studies Using Whole Body Nuclear Scintigraphy and SPECT-CT.

PubMed

Ali, Mohammad Javed; Vyakaranam, Achyut Ram; Rao, Jyotsna Eleshwarapu; Prasad, Giri; Reddy, Palkonda Vijay Anand

The objective of this study was to evaluate the influence of dose on nasal localization of radioactive iodine-131 (I-131) following therapy for differentiated thyroid carcinomas. Retrospective evaluation of all patients who underwent post-therapy I-131 whole body scintigraphy and single photon emission computed tomography was performed. Patients were divided into 2 groups; group A were treated with 100 millicurie (mCi) and group B with ≥150 mCi. Databases were reviewed for demographics, diagnosis, and administered dosage of I-131. Whole body scintigraphy images were retrieved and nasal uptake was analyzed and classified as nil to trace, low, moderate, and high uptake and corresponding single photon emission CTs were analyzed for radioactive nasal activity. A total of 100 patients were studied, 50 in each of the groups. The M:F ratio was 1.1:1 (27:23) in group A and 1.5:1 (30:20) in group B. The mean age was 43.12 years and 54.6 years in groups A and B, respectively. Papillary carcinoma of the thyroid was the most common type accounting for 82% (41/50) of patients in group A and 62% (31/50) in group B. Imaging studies revealed nil to trace nasal activity in 80% (40/50) in group A as compared with 56% (28/50) in group B. None of the patients in group A showed high nasal uptake, whereas 4% (2/50) in group B demonstrated such high activity. Intranasal localization of radioactive I-131 was significant in patients receiving a dose of ≥150 mCi. Intranasal localization may partly explain toxicity to nasolacrimal duct and may be a risk factor for subsequent development of nasolacrimal duct obstructions.

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

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

The Quest for Evidence for Proton Therapy: Model-Based Approach and Precision Medicine

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

Widder, Joachim, E-mail: j.widder@umcg.nl; Schaaf, Arjen van der; Lambin, Philippe

Purpose: Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. Methods and Materials: Dutch scientific and health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment. Results: By analogy with biologically targeted therapies, the technology needs to be testedmore » in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results. Conclusions: Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy.« 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.

Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy

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

Berbeco, Ross I., E-mail: rberbeco@partners.org; Detappe, Alexandre; Tsiamas, Panogiotis

2016-01-15

Purpose: Previous studies have introduced gold nanoparticles as vascular-disrupting agents during radiation therapy. Crucial to this concept is the low energy photon content of the therapy radiation beam. The authors introduce a new mode of delivery including a linear accelerator target that can toggle between low Z and high Z targets during beam delivery. In this study, the authors examine the potential increase in tumor blood vessel endothelial cell radiation dose enhancement with the low Z target. Methods: The authors use Monte Carlo methods to simulate delivery of three different clinical photon beams: (1) a 6 MV standard (Cu/W) beam,more » (2) a 6 MV flattening filter free (Cu/W), and (3) a 6 MV (carbon) beam. The photon energy spectra for each scenario are generated for depths in tissue-equivalent material: 2, 10, and 20 cm. The endothelial dose enhancement for each target and depth is calculated using a previously published analytic method. Results: It is found that the carbon target increases the proportion of low energy (<150 keV) photons at 10 cm depth to 28% from 8% for the 6 MV standard (Cu/W) beam. This nearly quadrupling of the low energy photon content incident on a gold nanoparticle results in 7.7 times the endothelial dose enhancement as a 6 MV standard (Cu/W) beam at this depth. Increased surface dose from the low Z target can be mitigated by well-spaced beam arrangements. Conclusions: By using the fast-switching target, one can modulate the photon beam during delivery, producing a customized photon energy spectrum for each specific situation.« less

Samarium-145 and its use as a radiation source

DOEpatents

Fairchild, Ralph G.; Laster, Brenda H.; Packer, Samuel

1989-09-05

The present invention covers a new radiation source, samarium-145, with radiation energies slightly above those of I-125 and a half-life of 340 days. The samarium-145 source is produced by neutron irradiation of SM-144. This new source is useful as the implanted radiation source in photon activation therapy of malignant tumors to activate the stable I-127 contained in the IdUrd accumulated in the tumor, causing radiation sensitization and Auger cascades that irreperably damage the tumor cells. This new source is also useful as a brachytherapy source.

Samarium-145 and its use as a radiation source

DOEpatents

Fairchild, Ralph G.; Laster, Brenda H.; Packer, Samuel

1989-01-01

The present invention covers a new radiation source, samarium-145, with radiation energies slightly above those of I-125 and a half-life of 340 days. The samarium-145 source is produced by neutron irradiation of SM-144. This new source is useful as the implanted radiation source in photon activation therapy of malignant tumors to activate the stable I-127 contained in the IdUrd accumulated in the tumor, causing radiation sensitization and Auger cascades that irreperably damage the tumor cells. This new source is also useful as a brachytherapy source.

Novel technologies and theoretical models in radiation therapy of cancer patients using 6.3 MeV fast neutrons produced by U-120 cyclotron

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

Musabaeva, L. I., E-mail: musabaevaLI@oncology.tomsk.ru; Lisin, V. A., E-mail: Lisin@oncology.tomsk.ru; Startseva, Zh. A., E-mail: zhanna.alex@rambler.ru

The analysis of clinical use of neutron therapy with 6 MeV fast neutrons compared to conventional radiation therapy was carried out. The experience of using neutron and mixed neutron and photon therapy in patients with different radio-resistant malignant tumors shows the necessity of further studies and development of the novel approaches to densely-ionizing radiation. The results of dosimetry and radiobiological studies have been the basis for planning clinical programs for neutron therapy. Clinical trials over the past 30 years have shown that neutron therapy successfully destroys radio-resistant cancers, including salivary gland tumors, adenoidcystic carcinoma, inoperable sarcomas, locally advanced head andmore » neck tumors, and locally advanced prostate cancer. Radiation therapy with 6.3 MeV fast neutrons used alone and in combination with photon therapy resulted in improved long-term treatment outcomes in patients with radio-resistant malignant tumors.« less

Antimicrobial Amino-Functionalized Nitrogen-Doped Graphene Quantum Dots for Eliminating Multidrug-Resistant Species in Dual-Modality Photodynamic Therapy and Bioimaging under Two-Photon Excitation.

PubMed

Kuo, Wen-Shuo; Shao, Yu-Ting; Huang, Keng-Shiang; Chou, Ting-Mao; Yang, Chih-Hui

2018-05-02

Developing a nanomaterial, for use in highly efficient dual-modality two-photon photodynamic therapy (PDT) involving reactive oxygen species (ROS) generation and for use as a two-photon imaging contrast probe, is currently desirable. Here, graphene quantum dots (GQDs) doped with nitrogen and functionalized with an amino group (amino-N-GQDs) serving as a photosensitizer in PDT had the superior ability to generate ROS as compared to unmodified GQDs. Multidrug-resistant (MDR) species were completely eliminated at an ultralow energy (239.36 nJ pixel -1 ) through only 12 s two-photon excitation (TPE) in the near-infrared region (800 nm). Furthermore, the amino-N-GQDs had an absorption wavelength of approximately 800 nm, quantum yield of 0.33, strong luminescence, an absolute cross section of approximately 54 356 Göeppert-Mayer units, a lifetime of 1.09 ns, a ratio of the radiative to nonradiative decay rates of approximately 0.49, and high two-photon stability under TPE. These favorable properties enabled the amino-N-GQDs to act as a two-photon contrast probe for tracking and localizing analytes through in-depth two-photon imaging in a three-dimensional biological environment and concurrently easily eliminating MDR species through PDT.

Treatment of extensive scalp lesions with segmental intensity-modulated photon therapy.

PubMed

Bedford, James L; Childs, Peter J; Hansen, Vibeke Nordmark; Warrington, Alan P; Mendes, Ruheena L; Glees, John P

2005-08-01

To compare static electron therapy, electron arc therapy, and photon intensity-modulated radiation therapy (IMRT) for treatment of extensive scalp lesions and to examine the dosimetric accuracy of the techniques. A retrospective treatment-planning study was performed to evaluate the relative merits of static electron fields, arcing electron fields, and five-field photon IMRT. Thermoluminescent dosimeters (TLD) were used to verify the accuracy of the techniques. The required thickness of bolus was investigated, and an anthropomorphic phantom was also used to examine the effects of air gaps between the wax bolus used for the IMRT technique and the patient's scalp. Neither static nor arcing electron techniques were able to provide a reliable coverage of the planning target volume (PTV), owing to obliquity of the fields in relation to the scalp. The IMRT technique considerably improved PTV dose uniformity, though it irradiated a larger volume of brain. Either 0.5 cm or 1.0 cm of wax bolus was found to be suitable. Air gaps of up to 1 cm between the bolus and the patient's scalp were correctly handled by the treatment-planning system and had negligible influence on the dose to the scalp. Photon IMRT provides a feasible alternative to electron techniques for treatment of large scalp lesions, resulting in improved homogeneity of dose to the PTV but with a moderate increase in dose to the brain.

Endoplasmic Reticulum-Localized Two-Photon-Absorbing Boron Dipyrromethenes as Advanced Photosensitizers for Photodynamic Therapy.

PubMed

Zhou, Yimin; Cheung, Ying-Kit; Ma, Chao; Zhao, Shirui; Gao, Di; Lo, Pui-Chi; Fong, Wing-Ping; Wong, Kam Sing; Ng, Dennis K P

2018-05-10

Two advanced boron dipyrromethene (BODIPY) based photosensitizers have been synthesized and characterized. With a glibenclamide analogous moiety, these compounds can localize in the endoplasmic reticulum (ER) of HeLa human cervical carcinoma cells and HepG2 human hepatocarcinoma cells. The BODIPY π skeleton is conjugated with two styryl or carbazolylethenyl groups, which can substantially red-shift the Q-band absorption and fluorescence emission and impart two-photon absorption (TPA) property to the chromophores. The TPA cross section of the carbazole-containing analogue reaches a value of 453 GM at 1010 nm. These compounds also behave as singlet oxygen generators with high photostability. Upon irradiation at λ > 610 nm, these photosensitizers cause photocytotoxicity to these two cell lines with IC 50 values down to 0.09 μM, for which the cell death is triggered mainly by ER stress. The two-photon photodynamic activity of the distyryl derivative upon excitation at λ = 800 nm has also been demonstrated.

Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique.

PubMed

Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna; Jensen, Alexandra; Haberer, Thomas; Jäkel, Oliver; Münter, Marc W; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

2011-12-01

PUROPOSE: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. In all 118 patients, few side effects were observed, in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility. Copyright © 2011 Elsevier Inc. All rights reserved.

Assessment of Early Toxicity and Response in Patients Treated With Proton and Carbon Ion Therapy at the Heidelberg Ion Therapy Center Using the Raster Scanning Technique

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

Rieken, Stefan; Habermehl, Daniel; Nikoghosyan, Anna

2011-12-01

Puropose: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center. Patients and Methods: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas. We evaluated early toxicity within 6 weeks after RT and the initial clinical and radiologic response for quality assurance in our new facility. Results: In all 118 patients, few side effects were observed,more » in particular, no high numbers of severe acute toxicity were found. In general, the patients treated with particle therapy alone showed only a few single side effects, mainly Radiation Therapy Oncology Group/Common Terminology Criteria grade 1. The most frequent side effects and cumulative incidence of single side effects were observed in the head-and-neck patients treated with particle therapy as a boost and photon intensity-modulated RT. The toxicities included common radiation-attributed reactions known from photon RT, including mucositis, dysphagia, and skin erythema. The most predominant imaging responses were observed in patients with high-grade gliomas and those with salivary gland tumors. For skull base tumors, imaging showed a stable tumor outline in most patients. Thirteen patients showed improvement of pre-existing clinical symptoms. Conclusions: Side effects related to particle treatment were rare, and the overall tolerability of the treatment was shown. The initial response was promising. The data have confirmed the safe delivery of carbon ions and protons at the newly opened Heidelberg facility.« less

Versatile Polymer Nanoparticles as Two-Photon-Triggered Photosensitizers for Simultaneous Cellular, Deep-Tissue Imaging, and Photodynamic Therapy.

PubMed

Guo, Liang; Ge, Jiechao; Liu, Qian; Jia, Qingyan; Zhang, Hongyan; Liu, Weimin; Niu, Guangle; Liu, Sha; Gong, Jianru; Hackbarth, Steffen; Wang, Pengfei

2017-06-01

Clinical applications of current photodynamic therapy (PDT) photosensitizers (PSs) are often limited by their absorption in the UV-vis range that possesses limited tissue penetration ability, leading to ineffective therapeutic response for deep-seated tumors. Alternatively, two-photon excited PS (TPE-PS) using NIR light triggered is one the most promising candidates for PDT improvement. Herein, multimodal polymer nanoparticles (PNPs) from polythiophene derivative as two-photon fluorescence imaging as well as two-photon-excited PDT agent are developed. The prepared PNPs exhibit excellent water dispersibility, high photostability and pH stability, strong fluorescence brightness, and low dark toxicity. More importantly, the PNPs also possess other outstanding features including: (1) the high 1 O 2 quantum yield; (2) the strong two-photon-induced fluorescence and efficient 1 O 2 generation; (3) the specific accumulation in lysosomes of HeLa cells; and (4) the imaging detection depth up to 2100 µm in the mock tissue under two-photon. The multifunctional PNPs are promising candidates as TPE-PDT agent for simultaneous cellular, deep-tissue imaging, and highly efficient in vivo PDT of cancer. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Lau, A; Chen, Y; Ahmad, S

Purpose: Proton therapy exhibits several advantages over photon therapy due to depth-dose distributions from proton interactions within the target material. However, uncertainties associated with protons beam range in the patient limit the advantage of proton therapy applications. To quantify beam range, positron-emitting nuclei (PEN) and prompt gamma (PG) techniques have been developed. These techniques use de-excitation photons to describe the location of the beam in the patient. To develop a detector system for implementing the PG technique for range verification applications in proton therapy, we studied the yields, energy and angular distributions of the secondary particles emitted from a PMMAmore » phantom. Methods: Proton pencil beams of various energies incident onto a PMMA phantom with dimensions of 5 x 5 x 50 cm3 were used for simulation with the Geant4 toolkit using the standard electromagnetic packages as well as the packages based on the binary-cascade nuclear model. The emitted secondary particles are analyzed . Results: For 160 MeV incident protons, the yields of secondary neutrons and photons per 100 incident protons were ~6 and ~15 respectively. Secondary photon energy spectrum showed several energy peaks in the range between 0 and 10 MeV. The energy peaks located between 4 and 6 MeV were attributed to originate from direct proton interactions with 12C (~ 4.4 MeV) and 16O (~ 6 MeV), respectively. Most of the escaping secondary neutrons were found to have energies between 10 and 100 MeV. Isotropic emissions were found for lower energy neutrons (<10 MeV) and photons for all energies, while higher energy neutrons were emitted predominantly in the forward direction. The yields of emitted photons and neutrons increased with the increase of incident proton energies. Conclusions: A detector system is currently being developed incorporating the yields, energy and angular distributions of secondary particles from proton interactions obtained from this study.« less

Proton or photon irradiation for hemangiomas of the choroid? A retrospective comparison

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

Hoecht, Stefan; Wachtlin, Joachim; Bechrakis, Nikolaos E.

2006-10-01

Purpose: The aim of this study was to compare, on a retrospective basis, the results of therapy in patients with uveal hemangioma treated with photon or proton irradiation at a single center. Methods and Materials: From 1993 to 2002 a total of 44 patients were treated. Until 1998 radiotherapy was given with 6 MV photons in standard fractionation of 2.0 Gy 5 times per week. In 1998 proton therapy became available and was used since then. A dose of 20 to 22.5 Cobalt Gray Equivalent (CGE) 68 MeV protons was given on 4 consecutive days. Progressive symptoms or deterioration ofmore » vision were the indications for therapy. Results: Of the 44 patients treated, 36 had circumscribed choroidal hemangiomas and 8 had diffuse choroidal hemangiomas (DCH) and Sturge-Weber syndrome. Of the patients, 19 were treated with photons with a total dose in the range of 16 to 30 Gy. A total of 25 patients were irradiated with protons. All patients with DCH but 1 were treated with photons. Stabilization of visual acuity was achieved in 93.2% of all patients. Tumor thickness decreased in 95.4% and retinal detachment resolved in 92.9%. Late effects, although generally mild or moderate, were frequently detected. In all, 40.9% showed radiation-induced optic neuropathy, maximum Grade I. Retinopathy was found in 29.5% of cases, but only 1 patient experienced more than Grade II severity. Retinopathy and radiation-induced optic neuropathy were reversible in some of the patients and in some resolved completely. No differences could be detected between patients with circumscribed choroidal hemangiomas treated with protons and photons. Treatment was less effective in DCH patients (75%). Conclusions: Radiotherapy is effective in treating choroidal hemangiomas with respect to visual acuity and tumor thickness but a benefit of proton therapy could not be detected. Side effects are moderate but careful monitoring for side effects should be part of the follow-up procedures.« less

Dose reduction of scattered photons from concrete walls lined with lead: Implications for improvement in design of megavoltage radiation therapy facility mazes.

PubMed

Al-Affan, I A M; Hugtenburg, R P; Bari, D S; Al-Saleh, W M; Piliero, M; Evans, S; Al-Hasan, M; Al-Zughul, B; Al-Kharouf, S; Ghaith, A

2015-02-01

This study explores the possibility of using lead to cover part of the radiation therapy facility maze walls in order to absorb low energy photons and reduce the total dose at the maze entrance of radiation therapy rooms. Experiments and Monte Carlo simulations were utilized to establish the possibility of using high-Z materials to cover the concrete walls of the maze in order to reduce the dose of the scattered photons at the maze entrance. The dose of the backscattered photons from a concrete wall was measured for various scattering angles. The dose was also calculated by the FLUKA and EGSnrc Monte Carlo codes. The FLUKA code was also used to simulate an existing radiotherapy room to study the effect of multiple scattering when adding lead to cover the concrete walls of the maze. Monoenergetic photons were used to represent the main components of the x ray spectrum up to 10 MV. It was observed that when the concrete wall was covered with just 2 mm of lead, the measured dose rate at all backscattering angles was reduced by 20% for photons of energy comparable to Co-60 emissions and 70% for Cs-137 emissions. The simulations with FLUKA and EGS showed that the reduction in the dose was potentially even higher when lead was added. One explanation for the reduction is the increased absorption of backscattered photons due to the photoelectric interaction in lead. The results also showed that adding 2 mm lead to the concrete walls and floor of the maze reduced the dose at the maze entrance by up to 90%. This novel proposal of covering part or the entire maze walls with a few millimeters of lead would have a direct implication for the design of radiation therapy facilities and would assist in upgrading the design of some mazes, especially those in facilities with limited space where the maze length cannot be extended to sufficiently reduce the dose. © 2015 American Association of Physicists in Medicine.

Dose reduction of scattered photons from concrete walls lined with lead: Implications for improvement in design of megavoltage radiation therapy facility mazes

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

Al-Affan, I. A. M., E-mail: info@medphys-environment.co.uk; Hugtenburg, R. P.; Piliero, M.

Purpose: This study explores the possibility of using lead to cover part of the radiation therapy facility maze walls in order to absorb low energy photons and reduce the total dose at the maze entrance of radiation therapy rooms. Methods: Experiments and Monte Carlo simulations were utilized to establish the possibility of using high-Z materials to cover the concrete walls of the maze in order to reduce the dose of the scattered photons at the maze entrance. The dose of the backscattered photons from a concrete wall was measured for various scattering angles. The dose was also calculated by themore » FLUKA and EGSnrc Monte Carlo codes. The FLUKA code was also used to simulate an existing radiotherapy room to study the effect of multiple scattering when adding lead to cover the concrete walls of the maze. Monoenergetic photons were used to represent the main components of the x ray spectrum up to 10 MV. Results: It was observed that when the concrete wall was covered with just 2 mm of lead, the measured dose rate at all backscattering angles was reduced by 20% for photons of energy comparable to Co-60 emissions and 70% for Cs-137 emissions. The simulations with FLUKA and EGS showed that the reduction in the dose was potentially even higher when lead was added. One explanation for the reduction is the increased absorption of backscattered photons due to the photoelectric interaction in lead. The results also showed that adding 2 mm lead to the concrete walls and floor of the maze reduced the dose at the maze entrance by up to 90%. Conclusions: This novel proposal of covering part or the entire maze walls with a few millimeters of lead would have a direct implication for the design of radiation therapy facilities and would assist in upgrading the design of some mazes, especially those in facilities with limited space where the maze length cannot be extended to sufficiently reduce the dose.« less

Proton and carbon ion radiotherapy for primary brain tumors delivered with active raster scanning at the Heidelberg Ion Therapy Center (HIT): early treatment results and study concepts

PubMed Central

2012-01-01

Background Particle irradiation was established at the University of Heidelberg 2 years ago. To date, more than 400 patients have been treated including patients with primary brain tumors. In malignant glioma (WHO IV) patients, two clinical trials have been set up-one investigating the benefit of a carbon ion (18 GyE) vs. a proton boost (10 GyE) in addition to photon radiotherapy (50 Gy), the other one investigating reirradiation with escalating total dose schedules starting at 30 GyE. In atypical meningioma patients (WHO °II), a carbon ion boost of 18 GyE is applied to macroscopic tumor residues following previous photon irradiation with 50 Gy. This study was set up in order to investigate toxicity and response after proton and carbon ion therapy for gliomas and meningiomas. Methods 33 patients with gliomas (n = 26) and meningiomas (n = 7) were treated with carbon ion (n = 26) and proton (n = 7) radiotherapy. In 22 patients, particle irradiation was combined with photon therapy. Temozolomide-based chemotherapy was combined with particle therapy in 17 patients with gliomas. Particle therapy as reirradiation was conducted in 7 patients. Target volume definition was based upon CT, MRI and PET imaging. Response was assessed by MRI examinations, and progression was diagnosed according to the Macdonald criteria. Toxicity was classified according to CTCAE v4.0. Results Treatment was completed and tolerated well in all patients. Toxicity was moderate and included fatigue (24.2%), intermittent cranial nerve symptoms (6%) and single episodes of seizures (6%). At first and second follow-up examinations, mean maximum tumor diameters had slightly decreased from 29.7 mm to 27.1 mm and 24.9 mm respectively. Nine glioma patients suffered from tumor relapse, among these 5 with infield relapses, causing death in 8 patients. There was no progression in any meningioma patient. Conclusions Particle radiotherapy is safe and feasible in patients with primary brain tumors. It is associated with little toxicity. A positive response of both gliomas and meningiomas, which is suggested in these preliminary data, must be evaluated in further clinical trials. PMID:22436135

Nonlinear optical and multiphoton processes for in situ manipulation and conversion of photons: applications to energy and healthcare (Conference Presentation)

NASA Astrophysics Data System (ADS)

Prasad, Paras N.

2017-02-01

Chiral control of nonlinear optical functions holds a great promise for a wide range of applications including optical signal processing, bio-sensing and chiral bio-imaging. In chiral polyfluorene thin films, we demonstrated extremely large chiral nonlinearity. The physics of manipulating excitation dynamics for photon transformation will be discussed, along with nanochemistry control of upconversion in hierarchically built organic chromophore coupled-core-multiple shell nanostructures which enable introduce new, organic-inorganic energy transfer routes for broadband light harvesting and increased upconversion efficiency via multistep cascaded energy transfer. We are pursuing the applications of photon conversion technology in IR harvesting for photovoltaics, high contrast bioimaging, photoacoustic imaging, photodynamic therapy, and optogenetics. An important application is in Brain research and Neurophotonics for functional mapping and modulation of brain activities. Another new direction pursued is magnetic field control of light in in a chiral polymer nanocomposite to achieve large magneto-optic coefficient which can enable sensing of extremely weak magnetic field due to brain waves. Finally, we will consider the thought provoking concept of utilizing photons to quantify, through magneto-optics, and augment - through nanoptogenetics, the cognitive states, thus paving the path way to a quantified human paradigm.

SU-F-T-485: Independent Remote Audits for TG51 NonCompliant Photon Beams Performed by the IROC Houston QA Center

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

Alvarez, P; Molineu, A; Lowenstein, J

Purpose: IROC-H conducts external audits for output check verification of photon and electron beams. Many of these beams can meet the geometric requirements of the TG 51 calibration protocol. For those photon beams that are non TG 51 compliant like Elekta GammaKnife, Accuray CyberKnife and TomoTherapy, IROC-H has specific audit tools to monitor the reference calibration. Methods: IROC-H used its TLD and OSLD remote monitoring systems to verify the output of machines with TG 51 non compliant beams. Acrylic OSLD miniphantoms are used for the CyberKnife. Special TLD phantoms are used for TomoTherapy and GammaKnife machines to accommodate the specificmore » geometry of each machine. These remote audit tools are sent to institutions to be irradiated and returned to IROC-H for analysis. Results: The average IROC-H/institution ratios for 480 GammaKnife, 660 CyberKnife and 907 rotational TomoTherapy beams are 1.000±0.021, 1.008±0.019, 0.974±0.023, respectively. In the particular case of TomoTherapy, the overall ratio is 0.977±0.022 for HD units. The standard deviations of all results are consistent with values determined for TG 51 compliant photon beams. These ratios have shown some changes compared to values presented in 2008. The GammaKnife results were corrected by an experimentally determined scatter factor of 1.025 in 2013. The TomoTherapy helical beam results are now from a rotational beam whereas in 2008 the results were from a static beam. The decision to change modality was based on recommendations from the users. Conclusion: External audits of beam outputs is a valuable tool to confirm the calibrations of photon beams regardless of whether the machine is TG 51 or TG 51 non compliant. The difference found for TomoTherapy units is under investigation. This investigation was supported by IROC grant CA180803 awarded by the NCI.« less

Two-Photon Absorbing Phosphorescent Metalloporphyrins: Effects of π-Extension and Peripheral Substitution.

PubMed

Esipova, Tatiana V; Rivera-Jacquez, Héctor J; Weber, Bruno; Masunov, Artëm E; Vinogradov, Sergei A

2016-12-07

The ability to form triplet excited states upon two-photon excitation is important for several applications of metalloporphyrins, including two-photon phosphorescence lifetime microscopy (2PLM) and two-photon photodynamic therapy (PDT). Here we analyzed one-photon (1P) and degenerate two-photon (2P) absorption properties of several phosphorescent Pt (II) porphyrins, focusing on the effects of aromatic π-extension and peripheral substitution on triplet emissivity and two-photon absorption (2PA). Our 2PA measurements for the first time made use of direct time-resolved detection of phosphorescence, having the ability to efficiently reject laser background through microsecond time gating. π-Extension of the porphyrin macrocycle by way of syn-fusion with two external aromatic fragments, such as in syn-dibenzo- (DBP) and syn-dinaphthoporphyrins (DNP), lowers the symmetry of the porphyrin skeleton. As a result, DBPs and DNPs exhibit stronger 2PA into the one-photon-allowed B (Soret) and Q states than fully symmetric (D 4h ) nonextended porphyrins. However, much more 2P-active states lie above the B state and cannot be accessed due to the interfering linear absorption. Alkoxycarbonyl groups (CO 2 R) in the benzo-rings dramatically enhance 2PA near the B state level. Time-dependent density functional theory (TDDFT) calculations in combinations with the sum-over-states (SOS) formalism revealed that the enhancement is due to the stabilization of higher-lying 2P-active states, which are dominated by the excitations involving orbitals extending onto the carbonyl groups. Furthermore, calculations predicted even stronger stabilization of the 2P-allowed gerade-states in symmetric Pt octaalkoxycarbonyl-tetrabenzoporphyrins. Experiments confirmed that the 2PA cross-section of PtTBP(CO 2 Bu) 8 near 810 nm reaches above 500 GM in spite of its completely centrosymmetric structure. Combined with exceptionally bright phosphorescence (ϕ phos = 0.45), strong 2PA makes Pt(II) complexes of π-extended porphyrins a valuable class of chromophores for 2P applications. Another important advantage of these porphyrinoids is their compact size and easily scalable synthesis.

SU-F-T-656: Monte Carlo Study On Air Activation Around a Medical Electron Linac

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

Horst, F; GSI Helmholtz Centre for Heavy Ion Research, Darmstadt; Fehrenbacher, G

Purpose: In high energy photon therapy, several radiation protection issues result from photonuclear reactions. The activation of air - directly by photonuclear reactions as well as indirectly by capture of photoneutrons generated inside the linac head - is a major point of concern for the medical staff. The purpose of this study was to estimate the annual effective dose to medical workers due to activated air around a medical high energy electron linac by means of Monte Carlo simulations. Methods: The treatment head of a Varian Clinac in 18 MV-X mode as well as the surrounding concrete bunker were modeledmore » and the radiation transport was simulated using the Monte Carlo code FLUKA, starting from the primary electron striking the bremsstrahlung target. The activation yields in air from photo-disintegration of O-16 and N-14 nuclei as well as from neutron capture on Ar-40 nuclei were obtained from the simulations. The activation build-up, radioactive decay and air ventilation were studied using a mathematical model. The annual effective dose to workers was estimated by using published isotope specific conversion factors. Results: The oxygen and nitrogen activation yields were in contrast to the argon activation yield found to be field size dependent. The impact of the treatment room ventilation on the different air activation products was investigated and quantified. An estimate with very conservative assumptions gave an annual effective dose to workers of < 1 mSv/a. Conclusion: From the results of this study it can be concluded that the contribution of air activation to the radiation exposure to medical workers should be negligible in modern photon therapy, especially when it is compared to the dose due to prompt neutrons and the activation of heavy solid materials such as the jaws and the collimators inside the linac head.« less

Fast Neutron Radiotherapy for Locally Advanced Prostate Cancer: Update of a Past Trial and Future Research Directions

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

Krieger, John N.; Krall, John M.; Laramore, George E.

1987-01-01

Between June, 1977 and April, 1983 the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III study comparing fast neutron radiotherapy as part of a mixed beam (neutron/photon) regimen with conventional photon (x-ray) radiotherapy for patients with locally advanced (stages C and o1 ) adenocarcinoma of the prostate. A total of 91 analyzable patients were entered into the study with -the two treatment groups being balanced in regard to all major prognostic variables. The current analysis is for a median follow-up of 6.7 years (range 3.4-9.0). Actuarial curves are presented for local/regional control, overall survival and "determinantal" survival. The resultsmore » are statistically significant in favor of the mixed beam group for all of the above parameters. At 5 years the local control rate is 81% on the mixed beam arm compared to 60% on the photon arm. Histologic evidence of residual prostatic carcinoma was documented in six patients with no clinical evidence of disease on both treatment arms. The actuarial overall survival rate at S years is 70% on the mixed beam compared to 56% on the photon arm. The determinantal survival at 5 years was 82%. on the mixed beam arm compared to 61% on the photon arm. The type of therapy appeared to be the most important predictor of both local tumor control and patient survival in a step-wise Cox analysis. There was no difference in the treatment related morbidity for the two patient groups. Mixed beam therapy may be superior to standard photon radiotherapy for treatment of locally advanced prostate cancer.« less

Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival

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

Eaton, Bree R.; Esiashvili, Natia; Kim, Sungjin

Purpose: The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. Methods and Materials: This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. Results: Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection,more » craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). Conclusions: Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma.« less

Photodynamic therapy and two-photon bio-imaging applications of hydrophobic chromophores through amphiphilic polymer delivery.

PubMed

Gallavardin, Thibault; Maurin, Mathieu; Marotte, Sophie; Simon, Timea; Gabudean, Ana-Maria; Bretonnière, Yann; Lindgren, Mikael; Lerouge, Frédéric; Baldeck, Patrick L; Stéphan, Olivier; Leverrier, Yann; Marvel, Jacqueline; Parola, Stéphane; Maury, Olivier; Andraud, Chantal

2011-07-01

The synthesis and photophysical properties of two lipophilic quadrupolar chromophores featuring anthracenyl (1) or dibromobenzene (2) were described. These two chromophores combined significant two-photon absorption cross-sections with high fluorescence quantum yield for 1 and improved singlet oxygen generation efficiency for 2, in organic solvents. The use of Pluronic nanoparticles allowed a simple and straightforward introduction of these lipophilic chromophores into biological cell media. Their internal distribution in various cell lines was studied using fluorescence microscopy and flow-cytometry following a successful staining that was achieved upon 2 h of incubation. Finally, multiphoton excitation microscopy and photodynamic therapy capability of the chromophores were demonstrated by cell exposure to a 820 nm fs laser and cell death upon one photon resonant irradiation at 436 ± 10 nm, respectively.

Multifunctional manganese-doped Prussian blue nanoparticles for two-photon photothermal therapy and magnetic resonance imaging.

PubMed

Ali, Lamiaa M A; Mathlouthi, Emna; Kajdan, Marilyn; Daurat, Morgane; Long, Jérôme; Sidi-Boulenouar, Rahima; Cardoso, Maïda; Goze-Bac, Christophe; Amdouni, Nourredine; Guari, Yannick; Larionova, Joulia; Gary-Bobo, Magali

2018-06-01

Here we demonstrate for the first time that Mn 2+ -doped Prussian blue nanoparticles of c.a. 70 nm act as effective agents for photothermal therapy under two-photon excitation with an almost total eradication of malignant cells (97 and 98%) at a concentration of 100 μg mL -1 24 h after NIR excitation. This effect combined with interesting longitudinal NMR relaxivity values offer new perspectives for effective imaging and cancer treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

The dosimetric effects of photon energy on the quality of prostate volumetric modulated arc therapy.

PubMed

Mattes, Malcolm D; Tai, Cyril; Lee, Alvin; Ashamalla, Hani; Ikoro, N C

2014-01-01

Studies comparing the dosimetric effects of high- and low-energy photons to treat prostate cancer using 3-dimensional conformal and intensity modulated radiation therapy have yielded mixed results. With the advent of newer radiation delivery systems like volumetric modulated arc therapy (VMAT), the impact of changing photon energy is readdressed. Sixty-five patients treated for prostate cancer at our institution from 2011 to 2012 underwent CT simulation. A target volume encompassing the prostate and entire seminal vesicles was treated to 50.4 Gy, followed by a boost to the prostate and proximal seminal vesicles to a total dose of 81 Gy. The VMAT plans were generated for 6-MV and 10-MV photons under identical optimization conditions using the Eclipse system version 8.6 (Varian Medical Systems, Palo Alto, CA). The analytical anisotropic algorithm was used for all dose calculations. Plans were normalized such that 98% of the planning target volume (PTV) received 100% of the prescribed dose. Dose-volumetric data from the treatment planning system was recorded for both 6-MV and 10-MV plans, which were compared for both the entire cohort and subsets of patients stratified according to the anterior-posterior separation. Plans using 10-MV photons had statistically significantly lower relative integral dose (4.1%), gradient measure (4.1%), skin Dmax (16.9%), monitor units (13.0%), and bladder V(30) (3.1%) than plans using 6-MV photons (P < .05). There was no difference in rectal dose, high-dose-region bladder dose, PTV coverage, or conformity index. The benefit of 10-MV photons was more pronounced for thicker patients (anterior-posterior separation >21 cm) for most parameters, with statistically significant differences in bladder V(30), bladder V(65), integral dose, conformity index, and monitor units. The main dosimetric benefits of 10-MV as compared with 6-MV photons are seen in thicker patients, though for the entire cohort 10-MV plans resulted in a lower integral dose, gradient measure, skin Dmax, monitor units, and bladder V(30), possibly at the expense of higher rectum V(81). Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

On-site audits to investigate the quality of radiation physics of radiation therapy institutions in the Republic of Korea.

PubMed

Park, Jong Min; Park, So-Yeon; Chun, Minsoo; Kim, Sang-Tae

2017-08-01

To investigate and improve the domestic standard of radiation therapy in the Republic of Korea. On-site audits were performed for 13 institutions in the Republic of Korea. Six items were investigated by on-site visits of each radiation therapy institution, including collimator, gantry, and couch rotation isocenter check; coincidence between light and radiation fields; photon beam flatness and symmetry; electron beam flatness and symmetry; physical wedge transmission factors; and photon beam and electron beam outputs. The average deviations of mechanical collimator, gantry, and couch rotation isocenter were less than 1mm. Those of radiation isocenter were also less than 1mm. The average difference between light and radiation fields was 0.9±0.6mm for the field size of 20cm×20cm. The average values of flatness and symmetry of the photon beams were 2.9%±0.6% and 1.1%±0.7%, respectively. Those of electron beams were 2.5%±0.7% and 0.6%±1.0%, respectively. Every institutions showed wedge transmission factor deviations less than 2% except one institution. The output deviations of both photon and electron beams were less than ±3% for every institution. Through the on-site audit program, we could effectively detect an inappropriately operating linacs and provide some recommendations. The standard of radiation therapy in Korea is expected to improve through such on-site audits. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

WE-FG-BRB-00: The Challenges of Predicting RBE Effects in Particle Therapy and Opportunities for Improving Cancer Therapy

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

NONE

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Poster — Thur Eve — 61: A new framework for MPERT plan optimization using MC-DAO

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

Baker, M; Lloyd, S AM; Townson, R

2014-08-15

This work combines the inverse planning technique known as Direct Aperture Optimization (DAO) with Intensity Modulated Radiation Therapy (IMRT) and combined electron and photon therapy plans. In particular, determining conditions under which Modulated Photon/Electron Radiation Therapy (MPERT) produces better dose conformality and sparing of organs at risk than traditional IMRT plans is central to the project. Presented here are the materials and methods used to generate and manipulate the DAO procedure. Included is the introduction of a powerful Java-based toolkit, the Aperture-based Monte Carlo (MC) MPERT Optimizer (AMMO), that serves as a framework for optimization and provides streamlined access tomore » underlying particle transport packages. Comparison of the toolkit's dose calculations to those produced by the Eclipse TPS and the demonstration of a preliminary optimization are presented as first benchmarks. Excellent agreement is illustrated between the Eclipse TPS and AMMO for a 6MV photon field. The results of a simple optimization shows the functioning of the optimization framework, while significant research remains to characterize appropriate constraints.« less

Biodegradable Photonic Melanoidin for Theranostic Applications.

PubMed

Lee, Min-Young; Lee, Changho; Jung, Ho Sang; Jeon, Mansik; Kim, Ki Su; Yun, Seok Hyun; Kim, Chulhong; Hahn, Sei Kwang

2016-01-26

Light-absorbing nanoparticles for localized heat generation in tissues have various biomedical applications in diagnostic imaging, surgery, and therapies. Although numerous plasmonic and carbon-based nanoparticles with strong optical absorption have been developed, their clearance, potential cytotoxicity, and long-term safety issues remain unresolved. Here, we show that "generally regarded as safe (GRAS)" melanoidins prepared from glucose and amino acid offer a high light-to-heat conversion efficiency, biocompatibility, biodegradability, nonmutagenicity, and efficient renal clearance, as well as a low cost for synthesis. We exhibit a wide range of biomedical photonic applications of melanoidins, including in vivo photoacoustic mapping of sentinel lymph nodes, photoacoustic tracking of gastrointestinal tracts, photothermal cancer therapy, and photothermal lipolysis. The biodegradation rate and renal clearance of melanoidins are controllable by design. Our results confirm the feasibility of biodegradable melanoidins for various photonic applications to theranostic nanomedicines.

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

Radiation-induced changes in gustatory function comparison of effects of neutron and photon irradiation

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

Mossman, K.L.; Chencharick, J.D.; Scheer, A.C.

1979-04-01

Changes in gustatory function were measured in 51 patients with various forms of cancer who received radiation to the head and neck region. Forty patients (group I) were treated with conventional photon radiation (e.g. 66 Gy/7 weeks), and 11 patients (group II) were treated with cyclotron produced fast neutrons (e.g. 22 Gy/7 weeks). Taste acuity was measured for four taste qualities (salt, sweet, sour, and bitter) by a forced choice-three stimulus drop technique which measured detection and recognition thresholds and by a forced scaling technique which measured taste intensity responsiveness. Subjective complaints of anorexia, dysgeusia, taste loss, and xerostomia weremore » also recorded. Patients were studied before, during and up to two months after therapy. Prior to therapy, detection and recognition thresholds, intensity responsiveness, and the frequency of subjective complaints in patients from groups I and II were statistically equivalent. During and up to 2 months after therapy, taste impairment and frequency of subjective complaints increased significantly in neutron and photon treated patients, but were statistically equivalent. Results of this study indicate that gustatory tissue response as measured by taste detection and recognition and intensity responsiveness, and the frequency of subjective complaints related to taste are statistically equivalent in patients before, during, or up 2 months after they were given either neutron or photon radiation for tumors of the head and neck.« less

Optimization of combined electron and photon beams for breast cancer

NASA Astrophysics Data System (ADS)

Xiong, W.; Li, J.; Chen, L.; Price, R. A.; Freedman, G.; Ding, M.; Qin, L.; Yang, J.; Ma, C.-M.

2004-05-01

Recently, intensity-modulated radiation therapy and modulated electron radiotherapy have gathered a growing interest for the treatment of breast and head and neck tumours. In this work, we carried out a study to combine electron and photon beams to achieve differential dose distributions for multiple target volumes simultaneously. A Monte Carlo based treatment planning system was investigated, which consists of a set of software tools to perform accurate dose calculation, treatment optimization, leaf sequencing and plan analysis. We compared breast treatment plans generated using this home-grown optimization and dose calculation software for different treatment techniques. Five different planning techniques have been developed for this study based on a standard photon beam whole breast treatment and an electron beam tumour bed cone down. Technique 1 includes two 6 MV tangential wedged photon beams followed by an anterior boost electron field. Technique 2 includes two 6 MV tangential intensity-modulated photon beams and the same boost electron field. Technique 3 optimizes two intensity-modulated photon beams based on a boost electron field. Technique 4 optimizes two intensity-modulated photon beams and the weight of the boost electron field. Technique 5 combines two intensity-modulated photon beams with an intensity-modulated electron field. Our results show that technique 2 can reduce hot spots both in the breast and the tumour bed compared to technique 1 (dose inhomogeneity is reduced from 34% to 28% for the target). Techniques 3, 4 and 5 can deliver a more homogeneous dose distribution to the target (with dose inhomogeneities for the target of 22%, 20% and 9%, respectively). In many cases techniques 3, 4 and 5 can reduce the dose to the lung and heart. It is concluded that combined photon and electron beam therapy may be advantageous for treating breast cancer compared to conventional treatment techniques using tangential wedged photon beams followed by a boost electron field.

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

Carlson, D.

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Dependences of mucosal dose on photon beams in head-and-neck intensity-modulated radiation therapy: a Monte Carlo study

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

Chow, James C.L., E-mail: james.chow@rmp.uhn.on.ca; Department of Radiation Oncology, University of Toronto, Toronto, Ontario; Department of Physics, Ryerson University, Toronto, Ontario

2012-07-01

Dependences of mucosal dose in the oral or nasal cavity on the beam energy, beam angle, multibeam configuration, and mucosal thickness were studied for small photon fields using Monte Carlo simulations (EGSnrc-based code), which were validated by measurements. Cylindrical mucosa phantoms (mucosal thickness = 1, 2, and 3 mm) with and without the bone and air inhomogeneities were irradiated by the 6- and 18-MV photon beams (field size = 1 Multiplication-Sign 1 cm{sup 2}) with gantry angles equal to 0 Degree-Sign , 90 Degree-Sign , and 180 Degree-Sign , and multibeam configurations using 2, 4, and 8 photon beams inmore » different orientations around the phantom. Doses along the central beam axis in the mucosal tissue were calculated. The mucosal surface doses were found to decrease slightly (1% for the 6-MV photon beam and 3% for the 18-MV beam) with an increase of mucosal thickness from 1-3 mm, when the beam angle is 0 Degree-Sign . The variation of mucosal surface dose with its thickness became insignificant when the beam angle was changed to 180 Degree-Sign , but the dose at the bone-mucosa interface was found to increase (28% for the 6-MV photon beam and 20% for the 18-MV beam) with the mucosal thickness. For different multibeam configurations, the dependence of mucosal dose on its thickness became insignificant when the number of photon beams around the mucosal tissue was increased. The mucosal dose with bone was varied with the beam energy, beam angle, multibeam configuration and mucosal thickness for a small segmental photon field. These dosimetric variations are important to consider improving the treatment strategy, so the mucosal complications in head-and-neck intensity-modulated radiation therapy can be minimized.« 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.

Heavy Charged Particle Radiobiology: Using Enhanced Biological Effectiveness and Improved Beam Focusing to Advance Cancer Therapy

PubMed Central

Allen, Christopher; Borak, Thomas B.; Tsujii, Hirohiko; Nickoloff, Jac A.

2011-01-01

Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. PMID:21376738

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.

Developing a treatment planning process and software for improved translation of photodynamic therapy

NASA Astrophysics Data System (ADS)

Cassidy, J.; Zheng, Z.; Xu, Y.; Betz, V.; Lilge, L.

2017-04-01

Background: The majority of de novo cancers are diagnosed in low and middle-income countries, which often lack the resources to provide adequate therapeutic options. None or minimally invasive therapies such as Photodynamic Therapy (PDT) or photothermal therapies could become part of the overall treatment options in these countries. However, widespread acceptance is hindered by the current empirical training of surgeons in these optical techniques and a lack of easily usable treatment optimizing tools. Methods: Based on image processing programs, ITK-SNAP, and the publicly available FullMonte light propagation software, a work plan is proposed that allows for personalized PDT treatment planning. Starting with, contoured clinical CT or MRI images, the generation of 3D tetrahedral models in silico, execution of the Monte Carlo simulation and presentation of the 3D fluence rate, Φ, [mWcm-2] distribution a treatment plan optimizing photon source placement is developed. Results: Permitting 1-2 days for the installation of the required programs, novices can generate their first fluence, H [Jcm-2] or Φ distribution in a matter of hours. This is reduced to 10th of minutes with some training. Executing the photon simulation calculations is rapid and not the performance limiting process. Largest sources of errors are uncertainties in the contouring and unknown tissue optical properties. Conclusions: The presented FullMonte simulation is the fastest tetrahedral based photon propagation program and provides the basis for PDT treatment planning processes, enabling a faster proliferation of low cost, minimal invasive personalized cancer therapies.

Single photon detection imaging of Cherenkov light emitted during radiation therapy

NASA Astrophysics Data System (ADS)

Adamson, Philip M.; Andreozzi, Jacqueline M.; LaRochelle, Ethan; Gladstone, David J.; Pogue, Brian W.

2018-03-01

Cherenkov imaging during radiation therapy has been developed as a tool for dosimetry, which could have applications in patient delivery verification or in regular quality audit. The cameras used are intensified imaging sensors, either ICCD or ICMOS cameras, which allow important features of imaging, including: (1) nanosecond time gating, (2) amplification by 103-104, which together allow for imaging which has (1) real time capture at 10-30 frames per second, (2) sensitivity at the level of single photon event level, and (3) ability to suppress background light from the ambient room. However, the capability to achieve single photon imaging has not been fully analyzed to date, and as such was the focus of this study. The ability to quantitatively characterize how a single photon event appears in amplified camera imaging from the Cherenkov images was analyzed with image processing. The signal seen at normal gain levels appears to be a blur of about 90 counts in the CCD detector, after going through the chain of photocathode detection, amplification through a microchannel plate PMT, excitation onto a phosphor screen and then imaged on the CCD. The analysis of single photon events requires careful interpretation of the fixed pattern noise, statistical quantum noise distributions, and the spatial spread of each pulse through the ICCD.

Theoretical study on photophysical properties of three high water solubility polypyridyl complexes for two-photon photodynamic therapy.

PubMed

Liu, Ying-Tao; Yin, Xue; Lai, Xiao-Yong; Wang, Xin

2018-06-22

Two-photon photodynamic therapy (TP-PDT) is a very promising treatment that has drawn much attention in recent years due to its ability to penetrate deeper into tissues and minimize the damage to normal cells. Here, the properties of three highly water soluble Ru(ii) and Zn(ii) polypyridyl complexes as photosensitizers (PSs) were examined, including the one-photon and two-photon absorption (OPA and TPA) spectra, singlet-triplet energy gap (ΔH-L), TPA cross-section and spin-orbit coupling constant via Density Function Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT). Their potential therapeutic use as photosensitizers in TP-PDT is proposed, where the reasoning is as follows: first, they possess strong absorption in the therapeutic window; second, the vertical excitation energy is greater than 0.98 eV, which can generate a singlet oxygen species and the remarkable coupling between the S1 and T1 states. Moreover, the spin-orbit matrix elements are greater than 0.24 cm-1 for Ru-bpy and Zn-tpy, indicating that the intersystem spin crossing processes are efficient. It is expected that these complexes will be applied to PSs in TP-PDT, and we hope this research can serve as a guideline for the development of efficient two-photon PSs.

WE-FG-BRB-04: RBEs for Human Lung Cancer Cells Exposed to Protons and Heavier Ions: Implications for Clinical Use of Charged Particles in Cancer Therapy

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

Held, K.

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Some computer graphical user interfaces in radiation therapy.

PubMed

Chow, James C L

2016-03-28

In this review, five graphical user interfaces (GUIs) used in radiation therapy practices and researches are introduced. They are: (1) the treatment time calculator, superficial X-ray treatment time calculator (SUPCALC) used in the superficial X-ray radiation therapy; (2) the monitor unit calculator, electron monitor unit calculator (EMUC) used in the electron radiation therapy; (3) the multileaf collimator machine file creator, sliding window intensity modulated radiotherapy (SWIMRT) used in generating fluence map for research and quality assurance in intensity modulated radiation therapy; (4) the treatment planning system, DOSCTP used in the calculation of 3D dose distribution using Monte Carlo simulation; and (5) the monitor unit calculator, photon beam monitor unit calculator (PMUC) used in photon beam radiation therapy. One common issue of these GUIs is that all user-friendly interfaces are linked to complex formulas and algorithms based on various theories, which do not have to be understood and noted by the user. In that case, user only needs to input the required information with help from graphical elements in order to produce desired results. SUPCALC is a superficial radiation treatment time calculator using the GUI technique to provide a convenient way for radiation therapist to calculate the treatment time, and keep a record for the skin cancer patient. EMUC is an electron monitor unit calculator for electron radiation therapy. Instead of doing hand calculation according to pre-determined dosimetric tables, clinical user needs only to input the required drawing of electron field in computer graphical file format, prescription dose, and beam parameters to EMUC to calculate the required monitor unit for the electron beam treatment. EMUC is based on a semi-experimental theory of sector-integration algorithm. SWIMRT is a multileaf collimator machine file creator to generate a fluence map produced by a medical linear accelerator. This machine file controls the multileaf collimator to deliver intensity modulated beams for a specific fluence map used in quality assurance or research. DOSCTP is a treatment planning system using the computed tomography images. Radiation beams (photon or electron) with different energies and field sizes produced by a linear accelerator can be placed in different positions to irradiate the tumour in the patient. DOSCTP is linked to a Monte Carlo simulation engine using the EGSnrc-based code, so that 3D dose distribution can be determined accurately for radiation therapy. Moreover, DOSCTP can be used for treatment planning of patient or small animal. PMUC is a GUI for calculation of the monitor unit based on the prescription dose of patient in photon beam radiation therapy. The calculation is based on dose corrections in changes of photon beam energy, treatment depth, field size, jaw position, beam axis, treatment distance and beam modifiers. All GUIs mentioned in this review were written either by the Microsoft Visual Basic.net or a MATLAB GUI development tool called GUIDE. In addition, all GUIs were verified and tested using measurements to ensure their accuracies were up to clinical acceptable levels for implementations.

WE-FG-BRB-01: Clinical Significance of RBE Variations in Proton Therapy

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

Paganetti, H.

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Nanoparticles as multimodal photon transducers of ionizing radiation

NASA Astrophysics Data System (ADS)

Pratt, Edwin C.; Shaffer, Travis M.; Zhang, Qize; Drain, Charles Michael; Grimm, Jan

2018-05-01

In biomedical imaging, nanoparticles combined with radionuclides that generate Cerenkov luminescence are used in diagnostic imaging, photon-induced therapies and as activatable probes. In these applications, the nanoparticle is often viewed as a carrier inert to ionizing radiation from the radionuclide. However, certain phenomena such as enhanced nanoparticle luminescence and generation of reactive oxygen species cannot be completely explained by Cerenkov luminescence interactions with nanoparticles. Herein, we report methods to examine the mechanisms of nanoparticle excitation by radionuclides, including interactions with Cerenkov luminescence, β particles and γ radiation. We demonstrate that β-scintillation contributes appreciably to excitation and reactivity in certain nanoparticle systems, and that excitation by radionuclides of nanoparticles composed of large atomic number atoms generates X-rays, enabling multiplexed imaging through single photon emission computed tomography. These findings demonstrate practical optical imaging and therapy using radionuclides with emission energies below the Cerenkov threshold, thereby expanding the list of applicable radionuclides.

An Assembled Nanocomplex for Improving both Therapeutic Efficiency and Treatment Depth in Photodynamic Therapy.

PubMed

Cao, Hongqian; Wang, Lei; Yang, Yang; Li, Juan; Qi, Yanfei; Li, Yue; Li, Ying; Wang, Hao; Li, Junbai

2018-06-25

Photodynamic therapy (PDT) shows unique selectivity and irreversible destruction toward treated tissues or cells, but still has several problems in clinical practice. One is limited therapeutic efficiency, which is attributed to hypoxia in tumor sites. Another is the limited treatment depth because traditional photosensitizes are excited by short wavelength light (<700 nm). An assembled nano-complex system composed of oxygen donor, two-photon absorption (TPA) species, and photosensitizer (PS) was synthesized to address both problems. The photosensitizer is excited indirectly by two-photon laser through intraparticle FRET mechanism for improving treatment depth. The oxygen donor, hemoglobin, can supply extra oxygen into tumor location through targeting effect for enhanced PDT efficiency. The mechanism and PDT effect were verified through both in vitro and in vivo experiments. The simple system is promising to promote two-photon PDT for clinical applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Morphology supporting function: attenuation correction for SPECT/CT, PET/CT, and PET/MR imaging

PubMed Central

Lee, Tzu C.; Alessio, Adam M.; Miyaoka, Robert M.; Kinahan, Paul E.

2017-01-01

Both SPECT, and in particular PET, are unique in medical imaging for their high sensitivity and direct link to a physical quantity, i.e. radiotracer concentration. This gives PET and SPECT imaging unique capabilities for accurately monitoring disease activity for the purposes of clinical management or therapy development. However, to achieve a direct quantitative connection between the underlying radiotracer concentration and the reconstructed image values several confounding physical effects have to be estimated, notably photon attenuation and scatter. With the advent of dual-modality SPECT/CT, PET/CT, and PET/MR scanners, the complementary CT or MR image data can enable these corrections, although there are unique challenges for each combination. This review covers the basic physics underlying photon attenuation and scatter and summarizes technical considerations for multimodal imaging with regard to PET and SPECT quantification and methods to address the challenges for each multimodal combination. PMID:26576737

Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor

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

Park, Lily; De Laney, Thomas F.; Liebsch, Norbert J.

2006-08-01

Purpose: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. Methods and Materials: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. Results: Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgerymore » and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received {>=}73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. Conclusion: These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by {>=}73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option.« less

SU-E-T-191: First Principle Calculation of Quantum Yield in Photodynamic Therapy

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

Abolfath, R; Guo, F; Chen, Z

Purpose: We present a first-principle method to calculate the spin transfer efficiency in oxygen induced by any photon fields especially in MeV energy range. The optical pumping is mediated through photosensitizers, e.g., porphyrin and/or ensemble of quantum dots. Methods: Under normal conditions, oxygen molecules are in the relatively non-reactive triplet state. In the presence of certain photosensitizer compounds such as porphyrins, electromagnetic radiation of specific wavelengths can excite oxygen to highly reactive singlet state. With selective uptake of photosensitizers by certain malignant cells, photon irradiation of phosensitized tumors can lead to selective killing of cancer cells. This is the basismore » of photodynamic therapy (PDT). Despite several attempts, PDT has not been clinically successful except in limited superficial cancers. Many parameters such as photon energy, conjugation with quantum dots etc. can be potentially combined with PDT in order to extend the role of PDT in cancer management. The key quantity for this optimization is the spin transfer efficiency in oxygen by any photon field. The first principle calculation model presented here, is an attempt to fill this need. We employ stochastic density matrix description of the quantum jumps and the rate equation methods in quantum optics based on Markov/Poisson processes and calculate time evolution of the population of the optically pumped singlet oxygen. Results: The results demonstrate the feasibility of our model in showing the dependence of the optical yield in generating spin-singlet oxygen on the experimental conditions. The adjustable variables can be tuned to maximize the population of the singlet oxygen hence the efficacy of the photodynamic therapy. Conclusion: The present model can be employed to fit and analyze the experimental data and possibly to assist researchers in optimizing the experimental conditions in photodynamic therapy.« less

Practice patterns of image guided particle therapy in Europe: A 2016 survey of the European Particle Therapy Network (EPTN).

PubMed

Bolsi, Alessandra; Peroni, Marta; Amelio, Dante; Dasu, Alexandru; Stock, Markus; Toma-Dasu, Iuliana; Nyström, Petra Witt; Hoffmann, Aswin

2018-03-28

Image guidance is critical in achieving accurate and precise radiation delivery in particle therapy, even more than in photon therapy. However, equipment, quality assurance procedures and clinical workflows for image-guided particle therapy (IGPT) may vary substantially between centres due to a lack of standardization. A survey was conducted to evaluate the current practice of IGPT in European particle therapy centres. In 2016, a questionnaire was distributed among 19 particle therapy centres in 12 European countries. The questionnaire consisted of 30 open and 37 closed questions related to image guidance in the general clinical workflow, for moving targets, current research activities and future perspectives of IGPT. All centres completed the questionnaire. The IGPT methods used by the 10 treating centres varied substantially. The 9 non-treating centres were in the process to introduce IGPT. Most centres have developed their own IGPT strategies, being tightly connected to their specific technical implementation and dose delivery methods. Insight into the current clinical practice of IGPT in European particle therapy centres was obtained. A variety in IGPT practices and procedures was confirmed, which underlines the need for harmonisation of practice parameters and consensus guidelines. Copyright © 2018 Elsevier B.V. All rights reserved.

SPECT/CT localization of oral radioiodine activity: a retrospective study and in-vitro assessment.

PubMed

Burlison, Jared S; Hartshorne, Michael F; Voda, Alan M; Cocks, Franklin H; Fair, Joanna R

2013-12-01

We sought to further localize radioiodine activity in the mouth on post-thyroid cancer therapy imaging using single-photon emission computed tomography/computed tomography (SPECT/CT). We retrospectively reviewed all patients (58) who underwent thyroid cancer therapy with iodine-131 (131I) at our institution from August 2009 to March 2011 whose post-therapy radioiodine imaging included neck SPECT/CT. A small group (six) of diagnostic 131I scans including SPECT/CT was also reviewed. Separately, we performed in-vitro 131I (sodium iodide) binding assays with amalgam and Argenco HP 77 (77% dental gold alloy) as proof of principle for these interactions. Of the 58 post-therapy patients, 45 (78%) had undergone metallic dental restorations, and of them 41 (91%) demonstrated oral 131I activity localizing preferentially to those restorations. It was observed that radioiodine also localized to other dental restorations and to orthodontic hardware. Gum-line activity in edentulous patients suggests radioiodine interaction with denture adhesive. In vitro, dental amalgam and Argenco HP 77 bound 131I in a time-dependent manner over 1-16 days of exposure. Despite subsequent washings with normal saline, significant 131I activity (maximally 12% for amalgam and 68% for Argenco HP 77) was retained by these metals. Subsequent soaking in a saturated solution of potassium iodide partially displaced 131I from amalgam, with near-total displacement of I from Argenco HP 77. SPECT/CT shows that radioiodine in the oral cavity localizes to metallic dental restorations. Furthermore, in-vitro studies demonstrate partially reversible binding of 131I to common dental metals.

Predicted Rate of Secondary Malignancies Following Adjuvant Proton Versus Photon Radiation Therapy for Thymoma.

PubMed

Vogel, J; Lin, L; Litzky, L A; Berman, A T; Simone, C B

2017-10-01

Thymic malignancies are the most common tumors of the anterior mediastinum. The benefit of adjuvant radiation therapy for stage II disease remains controversial, and patients treated with adjuvant radiation therapy are at risk of late complications, including radiation-induced secondary malignant neoplasms (SMNs), that may reduce the overall benefit of treatment. We assess the risk of predicted SMNs following adjuvant proton radiation therapy compared with photon radiation therapy after resection of stage II thymic malignancies to determine whether proton therapy improves the risk-benefit ratio. Ten consecutive patients treated with double-scattered proton beam radiation therapy (DS-PBT) were prospectively enrolled in an institutional review board-approved proton registry study. All patients were treated with DS-PBT. Intensity modulated radiation therapy (IMRT) plans for comparison were generated. SMN risk was calculated based on organ equivalent dose. Patients had a median age of 65 years (range, 25-77 years), and 60% were men. All patients had stage II disease, and many had close or positive margins (60%). The median dose was 50.4 Gy (range, 50.4-54.0 Gy) in 1.8-Gy relative biological effectiveness daily fractions. No differences in target coverage were seen with DS-PBT compared with IMRT plans. Significant reductions were seen in mean and volumetric lung, heart, and esophageal doses with DS-PBT compared with IMRT plans (all P≤.01). Significant reductions in SMNs in the lung, breast, esophagus, skin, and stomach were seen with DS-PBT compared with IMRT. For patients with thymoma diagnosed at the median national age, 5 excess secondary malignancies per 100 patients would be avoided by treating them with protons instead of photons. Treatment with proton therapy can achieve comparable target coverage but significantly reduced doses to critical normal structures, which can lead to fewer predicted SMNs compared with IMRT. By decreasing expected late complications, proton therapy may improve the therapeutic ratio of adjuvant radiation therapy for patients with stage II thymic malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

Potential hazard due to induced radioactivity secondary to radiotherapy: the report of task group 136 of the American Association of Physicists in Medicine.

PubMed

Thomadsen, Bruce; Nath, Ravinder; Bateman, Fred B; Farr, Jonathan; Glisson, Cal; Islam, Mohammad K; LaFrance, Terry; Moore, Mary E; George Xu, X; Yudelev, Mark

2014-11-01

External-beam radiation therapy mostly uses high-energy photons (x-rays) produced by medical accelerators, but many facilities now use proton beams, and a few use fast-neutron beams. High-energy photons offer several advantages over lower-energy photons in terms of better dose distributions for deep-seated tumors, lower skin dose, less sensitivity to tissue heterogeneities, etc. However, for beams operating at or above 10 MV, some of the materials in the accelerator room and the radiotherapy patient become radioactive due primarily to photonuclear reactions and neutron capture, exposing therapy staff and patients to unwanted radiation dose. Some recent advances in radiotherapy technology require treatments using a higher number of monitor units and monitor-unit rates for the same delivered dose, and compared to the conventional treatment techniques and fractionation schemes, the activation dose to personnel can be substantially higher. Radiotherapy treatments with proton and neutron beams all result in activated materials in the treatment room. In this report, the authors review critically the published literature on radiation exposures from induced radioactivity in radiotherapy. They conclude that the additional exposure to the patient due to induced radioactivity is negligible compared to the overall radiation exposure as a part of the treatment. The additional exposure to the staff due to induced activity from photon beams is small at an estimated level of about 1 to 2 mSv y. This is well below the allowed occupational exposure limits. Therefore, the potential hazard to staff from induced radioactivity in the use of high-energy x-rays is considered to be low, and no specific actions are considered necessary or mandatory. However, in the spirit of the "As Low as Reasonably Achievable (ALARA)" program, some reasonable steps are recommended that can be taken to reduce this small exposure to an even lower level. The dose reduction strategies suggested should be followed only if these actions are considered reasonable and practical in the individual clinics. Therapists working with proton beam and neutron beam units handle treatment devices that do become radioactive, and they should wear extremity monitors and make handling apertures and boluses their last task upon entering the room following treatment. Personnel doses from neutron-beam units can approach regulatory limits depending on the number of patients and beams, and strategies to reduce doses should be followed.

Evaluation of a mixed beam therapy for post-mastectomy breast cancer patients: bolus electron conformal therapy combined with intensity modulated photon radiotherapy and volumetric modulated photon arc therapy.

PubMed

Zhang, Rui; Heins, David; Sanders, Mary; Guo, Beibei; Hogstrom, Kenneth

2018-05-10

The purpose of this study was to assess the potential benefits and limitations of a mixed beam therapy, which combined bolus electron conformal therapy (BECT) with intensity modulated photon radiotherapy (IMRT) and volumetric modulated photon arc therapy (VMAT), for left-sided post-mastectomy breast cancer patients. Mixed beam treatment plans were produced for nine post-mastectomy radiotherapy (PMRT) patients previously treated at our clinic with VMAT alone. The mixed beam plans consisted of 40 Gy to the chest wall area using BECT, 40 Gy to the supraclavicular area using parallel opposed IMRT, and 10 Gy to the total planning target volume (PTV) by optimizing VMAT on top of the BECT+IMRT dose distribution. The treatment plans were created in a commercial treatment planning system (TPS), and all plans were evaluated based on PTV coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP), and secondary cancer complication probability (SCCP). The standard VMAT alone planning technique was used as the reference for comparison. Both techniques produced clinically acceptable PMRT plans but with a few significant differences: VMAT showed significantly better CI (0.70 vs. 0.53, p < 0.001) and DHI (0.12 vs. 0.20, p < 0.001) over mixed beam therapy. For normal tissues, mixed beam therapy showed better OAR sparing and significantly reduced NTCP for cardiac mortality (0.23% vs. 0.80%, p = 0.01) and SCCP for contralateral breast (1.7% vs. 3.1% based on linear model, and 1.2% vs. 1.9% based on linear-exponential model, p < 0.001 in both cases), but showed significantly higher mean (50.8 Gy vs. 49.3 Gy, p < 0.001) and maximum skin doses (59.7 Gy vs. 53.3 Gy, p < 0.001) compared with VMAT. Patients with more tissue (minimum distance between the distal PTV surface and lung approximately > 0.5 cm and volume of tissue between the distal PTV surface and heart or lung approximately > 250 cm 3 ) between distal PTV surface and lung may benefit the most from mixed beam therapy. This work has demonstrated that mixed beam therapy (BECT+IMRT : VMAT = 4 : 1) produces clinically acceptable plans having reduced OAR doses and risks of side effects compared with VMAT. Even though VMAT alone produces more homogenous and conformal dose distributions, mixed beam therapy remains as a viable option for treating post-mastectomy patients, possibly leading to reduced normal tissue complications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Comparision of beam data requirements for MLC commissioning on a TPS

NASA Astrophysics Data System (ADS)

Solaiappan, Gopi; Singaravelu, Ganesan; Prakasarao, Aruna; Supe, Sanjay S.

2008-01-01

The treatment planning system (TPS) has become a key element in the radiotherapy process with the introduction of computer tomography (CT) based 3D conformal treatment planning. Commissioning of a MLC on a TPS either for conformal radiotherapy or intensity modulated radiation therapy (IMRT) requires beam data to be generated on a linear accelerator. Most of the TPS require these beam data to be generated with routine collimator jaws. However some TPS demand the data to be provided for MLC shaped fields. This prompted us to investigate whether beam data with jaws differ than that with MLC and whether the jaw based beam data would suffice for the commissioning of a MLC on a TPS. Beam data like percentage depth dose (PDD), cross beam profiles and output factors was acquired for jaws and MLC defined square fields for 6, 10 and 23 MV photon beams. Percentage depth dose and cross beam profiles were acquired with a radiation field analyzer RFA-200, CC13-S ion chambers with active volume of 0.13 cm3 and OmniPro-Accept software from Scanditronix-Wellhofer. A Medtec-TG51 water tank with Max-4000 electrometer and 0.6 cc PTW ionization chamber and a mini phantom from Standard Imaging was utilized for output measurements for millennium-120 MLC (Varian Medical Systems) and SRS diode detector (Scanditronix-Wellhofer) of 0.6 mm diameter of active area and 0.3 mm of active volume thickness for micro-MLC (BrainLab). The difference in PDD in the build-up region for millennium MLC was ±1.0% for 6 MV photons. For 10 MV photons the PDD difference was within ±4.0%. The difference in PDD for 23 MV photons ranged from 0% to 40.0%. PDD difference from build-up depth to about 28 cm was within ±1.0%. Difference in PDD crossed ±1.0% at 30 cm depth for 6 MV photons. The difference in PDD in the build-up region for mMLC was ±8.0% for 6 MV photons. For the smallest field size studied with micro-MLC i.e. 0.6 × 0.6 cm2 difference in PDD was more than ±1.0% in the build-up region and beyond a depth of 8.0 cm. The profiles for jaws and MLC agreed within the umbra region. However in the penumbra region small differences in doses were observed. The collimator scatter factor (Sc), phantom scatter factor (Sp) and output factor values for MLC were different that those for jaws. The differences in beam characteristics could have implication for intensity modulated radiation therapy and stereotactic radiosurgery in terms of dose in the build up region, exit dose, dose to the planning target volume (PTV) and organ at risk (OAR). Impact of these dosimetric differences between jaw and MLC needs to be further studied in terms of dose volume histograms for PTV and OAR and its further impact on tumor control probability (TCP) and normal tissue complication probability (NTCP).

Sci—Thur AM: YIS - 03: irtGPUMCD: a new GPU-calculated dosimetry code for {sup 177}Lu-octreotate radionuclide therapy of neuroendocrine tumors

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

Montégiani, Jean-François; Gaudin, Émilie; Després, Philippe

2014-08-15

In peptide receptor radionuclide therapy (PRRT), huge inter-patient variability in absorbed radiation doses per administered activity mandates the utilization of individualized dosimetry to evaluate therapeutic efficacy and toxicity. We created a reliable GPU-calculated dosimetry code (irtGPUMCD) and assessed {sup 177}Lu-octreotate renal dosimetry in eight patients (4 cycles of approximately 7.4 GBq). irtGPUMCD was derived from a brachytherapy dosimetry code (bGPUMCD), which was adapted to {sup 177}Lu PRRT dosimetry. Serial quantitative single-photon emission computed tomography (SPECT) images were obtained from three SPECT/CT acquisitions performed at 4, 24 and 72 hours after {sup 177}Lu-octreotate administration, and registered with non-rigid deformation of CTmore » volumes, to obtain {sup 177}Lu-octreotate 4D quantitative biodistribution. Local energy deposition from the β disintegrations was assumed. Using Monte Carlo gamma photon transportation, irtGPUMCD computed dose rate at each time point. Average kidney absorbed dose was obtained from 1-cm{sup 3} VOI dose rate samples on each cortex, subjected to a biexponential curve fit. Integration of the latter time-dose rate curve yielded the renal absorbed dose. The mean renal dose per administered activity was 0.48 ± 0.13 Gy/GBq (range: 0.30–0.71 Gy/GBq). Comparison to another PRRT dosimetry code (VRAK: Voxelized Registration and Kinetics) showed fair accordance with irtGPUMCD (11.4 ± 6.8 %, range: 3.3–26.2%). These results suggest the possibility to use the irtGPUMCD code in order to personalize administered activity in PRRT. This could allow improving clinical outcomes by maximizing per-cycle tumor doses, without exceeding the tolerable renal dose.« less

Choosing a therapy electron accelerator target.

PubMed

Hutcheon, R M; Schriber, S O; Funk, L W; Sherman, N K

1979-01-01

Angular distributions of photon depth dose produced by 25-MeV electrons incident on several fully stopping single-element targets (C, Al, Cu, Mo, Ta, Pb) and two composite layered targets (Ni-Al, W-Al) were studied. Depth-dose curves measured using TLD-700 (thermoluminescent dosimeter) chips embedded in lucite phantoms. Several useful therapy electron accelerator design curves were determined, including relative flattener thickness as a function of target atomic number, "effective" bremsstrahlung endpoint energy or beam "hardness" as a function of target atomic number and photon emission angle, and estimates of shielding thickness as a function of angle required to reduce the radiation outside the treatment cone to required levels.

Clinical outcomes using carbon-ion radiotherapy and dose-volume histogram comparison between carbon-ion radiotherapy and photon therapy for T2b-4N0M0 non-small cell lung cancer-A pilot study.

PubMed

Shirai, Katsuyuki; Kawashima, Motohiro; Saitoh, Jun-Ichi; Abe, Takanori; Fukata, Kyohei; Shigeta, Yuka; Irie, Daisuke; Shiba, Shintaro; Okano, Naoko; Ohno, Tatsuya; Nakano, Takashi

2017-01-01

The safety and efficacy of carbon-ion radiotherapy for advanced non-small cell lung cancer have not been established. We evaluated the clinical outcomes and dose-volume histogram parameters of carbon-ion radiotherapy compared with photon therapy in T2b-4N0M0 non-small cell lung cancer. Twenty-three patients were treated with carbon-ion radiotherapy between May 2011 and December 2015. Seven, 14, and 2 patients had T2b, T3, and T4, respectively. The median age was 78 (range, 53-91) years, with 22 male patients. There were 12 adenocarcinomas, 8 squamous cell carcinomas, 1 non-small cell lung carcinoma, and 2 clinically diagnosed lung cancers. Eleven patients were operable, and 12 patients were inoperable. Most patients (91%) were treated with carbon-ion radiotherapy of 60.0 Gy relative biological effectiveness (RBE) in 4 fractions or 64.0 Gy (RBE) in 16 fractions. Local control and overall survival rates were calculated. Dose-volume histogram parameters of normal lung and tumor coverages were compared between carbon-ion radiotherapy and photon therapies, including three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). The median follow-up of surviving patients was 25 months. Three patients experienced local recurrence, and the 2-year local control rate was 81%. During follow-up, 5 patients died of lung cancer, and 1 died of intercurrent disease. The 2-year overall survival rate was 70%. Operable patients had a better overall survival rate compared with inoperable patients (100% vs. 43%; P = 0.04). There was no grade ≥2 radiation pneumonitis. In dose-volume histogram analysis, carbon-ion radiotherapy had a significantly lower dose to normal lung and greater tumor coverage compared with photon therapies. Carbon-ion radiotherapy was effectively and safely performed for T2b-4N0M0 non-small cell lung cancer, and the dose distribution was superior compared with those for photon therapies. A Japanese multi-institutional study is ongoing to prospectively evaluate these patients and establish the use of carbon-ion radiotherapy.

Pion radiation for high grade astrocytoma: results of a randomized study.

PubMed

Pickles, T; Goodman, G B; Rheaume, D E; Duncan, G G; Fryer, C J; Bhimji, S; Ludgate, C; Syndikus, I; Graham, P; Dimitrov, M; Bowen, J

1997-02-01

This study attempted to compare within a randomized study the outcome of pion radiation therapy vs. conventional photon irradiation for the treatment of high-grade astrocytomas. Eighty-four patients were randomized to pion therapy (33-34.5 Gy pi), or conventional photon irradiation (60 Gy). Entry criteria included astrocytoma (modified Kernohan high Grade 3 or Grade 4), age 18-70, Karnofsky performance status (KPS) > or = 50, ability to start irradiation within 30 days of surgery, unifocal tumor, and treatment volume < 850 cc. The high-dose volume in both arms was computed tomography enhancement plus a 2-cm margin. The study was designed with the power to detect a twofold difference between arms. Eighty-one eligible patients were equally balanced for all known prognostic variables. Pion patients started radiation 7 days earlier on average than photon patients, but other treatment-related variables did not differ. There were no significant differences for either early or late radiation toxicity between treatment arms. Actuarial survival analysis shows no differences in terms of time to local recurrence or overall survival where median survival was 10 months in both arms (p = 0.22). The physician-assessed KPS and patient-assessed quality of life (QOL) measurements were generally maintained within 10 percentage points until shortly before tumor recurrence. There was no apparent difference in the serial KPS or QOL scores between treatment arms. In contrast to high linear energy transfer (LET) therapy for central nervous system tumors, such as neutron or neon therapy, the safety of pion therapy, which is of intermediate LET, has been reaffirmed. However, this study has demonstrated no therapeutic gain for pion therapy of glioblastoma.

Impact of the NTCP modeling on medical decision to select eligible patient for proton therapy: the usefulness of EUD as an indicator to rank modern photon vs proton treatment plans.

PubMed

Chaikh, Abdulhamid; Calugaru, Valentin; Bondiau, Pierre-Yves; Thariat, Juliette; Balosso, Jacques

2018-06-07

The aim of this study is to evaluate the impact of normal tissue complication probability (NTCP)-based radiobiological models on the estimated risk for late radiation lung damages. The second goal is to propose a medical decision-making approach to select the eligible patient for particle therapy. 14 pediatric patients undergoing cranio-spinal irradiation were evaluated. For each patient, two treatment plans were generated using photon and proton therapy with the same dose prescriptions. Late radiation damage to lung was estimated using three NTCP concepts: the Lyman-Kutcher-Burman, the equivalent uniform dose (EUD) and the mean lung dose according to the quantitative analysis of normal tissue effects in the clinic QUANTEC review. Wilcoxon paired test was used to calculate p-value. Proton therapy achieved lower lung EUD (Gy). The average NTCP values were significantly lower with proton plans, p < 0.05, using the three NTCP concepts. However, applying the same TD 50/5 using radiobiological models to compare NTCP from proton and photon therapy, the ΔNTCP was not a convincing method to measure the potential benefit of proton therapy. Late radiation pneumonitis estimated from the mean lung dose model correlated with QUANTEC data better. treatment effectiveness assessed on NTCP reduction depends on radiobiological predictions and parameters used as inputs for in silico evaluation. Since estimates of absolute NTCP values from LKB and GN models are imprecise due to EUD ≪ TD 50/5 , a reduction of the EUD value with proton plans would better predict a reduction of dose/toxicity. The EUD concept appears as a robust radiobiological surrogate of the dose distribution to select the optimal patient's plan.

Applications of Molecular Imaging

PubMed Central

Galbán, Craig; Galbán, Stefanie; Van Dort, Marcian; Luker, Gary D.; Bhojani, Mahaveer S.; Rehemtualla, Alnawaz; Ross, Brian D.

2015-01-01

Today molecular imaging technologies play a central role in clinical oncology. The use of imaging techniques in early cancer detection, treatment response and new therapy development is steadily growing and has already significantly impacted clinical management of cancer. In this chapter we will overview three different molecular imaging technologies used for the understanding of disease biomarkers, drug development, or monitoring therapeutic outcome. They are (1) optical imaging (bioluminescence and fluorescence imaging) (2) magnetic resonance imaging (MRI), and (3) nuclear imaging (e.g, single photon emission computed tomography (SPECT) and positron emission tomography (PET)). We will review the use of molecular reporters of biological processes (e.g. apoptosis and protein kinase activity) for high throughput drug screening and new cancer therapies, diffusion MRI as a biomarker for early treatment response and PET and SPECT radioligands in oncology. PMID:21075334

Two-Photon Activation of p-Hydroxyphenacyl Phototriggers: Toward Spatially Controlled Release of Diethyl Phosphate and ATP.

PubMed

Houk, Amanda L; Givens, Richard S; Elles, Christopher G

2016-03-31

Two-photon activation of the p-hydroxyphenacyl (pHP) photoactivated protecting group is demonstrated for the first time using visible light at 550 nm from a pulsed laser. Broadband two-photon absorption measurements reveal a strong two-photon transition (>10 GM) near 4.5 eV that closely resembles the lowest-energy band at the same total excitation energy in the one-photon absorption spectrum of the pHP chromophore. The polarization dependence of the two-photon absorption band is consistent with excitation to the same S3 ((1)ππ*) excited state for both one- and two-photon activation. Monitoring the progress of the uncaging reaction under nonresonant excitation at 550 nm confirms a quadratic intensity dependence and that two-photon activation of the uncaging reaction is possible using visible light in the range 500-620 nm. Deprotonation of the pHP chromophore under mildly basic conditions shifts the absorption band to lower energy (3.8 eV) in both the one- and two-photon absorption spectra, suggesting that two-photon activation of the pHP chromophore may be possible using light in the range 550-720 nm. The results of these measurements open the possibility of spatially and temporally selective release of biologically active compounds from the pHP protecting group using visible light from a pulsed laser.

Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy.

PubMed

Allen, Christopher; Borak, Thomas B; Tsujii, Hirohiko; Nickoloff, Jac A

2011-06-03

Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. 2011 Elsevier B.V. All rights reserved.

WE-FG-BRB-02: Spatial Mapping of the RBE of Scanned Particle Beams

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

Grosshans, D.

2016-06-15

The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences betweenmore » particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to provide higher levels of local tumor control and improved normal tissue sparing will be discussed. Learning Objectives: To assess whether the current practice of a constant RBE of 1.1 should be revised or maintained in proton therapy and to evaluate the potential clinical consequences of delivering RBE-weighted dose distributions based on variable RBE To review current research on biological models used to predict the increased biological effectiveness of proton and carbon ions to help move towards a practical understanding and implementation of biological optimization in particle therapy To discuss potential differences in biological mechanisms between photons and charged particles (light and heavy ions) that could impact clinical cancer therapy H. Paganetti, NCI U19 CA21239D. Grosshans, Our research is supported by the NCIK. Held, Funding Support: National Cancer Institute of the National Institutes of Health, USA, under Award Number R21CA182259 and Federal Share of Program Income Earned by Massachusetts General Hospital on C06CA059267, Proton Therapy Research and Treatment Center.« less

Photonic modulation of EGFR: 280nm low level light arrests cancer cell activation and migration

NASA Astrophysics Data System (ADS)

Botelho, Cláudia M.; Marques, Rogério; Viruthachalam, Thiagarajan; Gonçalves, Odete; Vorum, Henrik; Gomes, Andreia C.; Neves-Petersen, Maria Teresa

2017-02-01

Overexpression of the Epidermal Growth Factor Receptor (EGFR) by cancer cells is associated with a poor prognosis for the patient. For several decades, therapies targeting EGFR have been designed, including the use of monoclonal antibodies and small molecule tyrosine kinase inhibitors. The use of these molecules had good clinical results, although its efficiency (and specificity) is still far from being optimal. In this paper, we present a new approach for a possible new cancer therapy targeting EGFR and using low intensity 280nm light. The influence of 280nm UVB illumination on cancer cells stimulated with 2nM of EGF was followed by time-lapse confocal microscopy. The 280nm illumination of the cancer cells blocks EGFR activation, inhibiting EGFR internalization and cell migration thus inhibiting the transition to the metastatic phenotype. Exposure time is a very important factor. The higher the illumination time the more significant differences were observed: 280nm light delayed or completely halted EGFR activation in the cell membrane, mainly at the cell junction level, and delayed or halted EGFR endocytic internalization, filopodia formation and cell migration.

Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy.

PubMed

Michalakis, Stylianos; Becirovic, Elvir; Biel, Martin

2018-03-07

The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG) channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca 2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and voltage-gated potassium channels (KCN). In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application.

Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy

PubMed Central

Biel, Martin

2018-01-01

The first step in vision is the absorption of photons by the photopigments in cone and rod photoreceptors. After initial amplification within the phototransduction cascade the signal is translated into an electrical signal by the action of cyclic nucleotide-gated (CNG) channels. CNG channels are ligand-gated ion channels that are activated by the binding of cyclic guanosine monophosphate (cGMP) or cyclic adenosine monophosphate (cAMP). Retinal CNG channels transduce changes in intracellular concentrations of cGMP into changes of the membrane potential and the Ca2+ concentration. Structurally, the CNG channels belong to the superfamily of pore-loop cation channels and share a common gross structure with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and voltage-gated potassium channels (KCN). In this review, we provide an overview on the molecular properties of CNG channels and describe their physiological role in the phototransduction pathways. We also discuss insights into the pathophysiological role of CNG channel proteins that have emerged from the analysis of CNG channel-deficient animal models and human CNG channelopathies. Finally, we summarize recent gene therapy activities and provide an outlook for future clinical application. PMID:29518895

Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

PubMed Central

Bowsher, James; Yan, Susu; Roper, Justin; Giles, William; Yin, Fang-Fang

2014-01-01

Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min scan times. PMID:24387490

Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

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

Bowsher, James, E-mail: james.bowsher@duke.edu; Giles, William; Yin, Fang-Fang

2014-01-15

Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinholemore » SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min scan times.« less

SU-E-T-238: Monte Carlo Estimation of Cerenkov Dose for Photo-Dynamic Radiotherapy

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

Chibani, O; Price, R; Ma, C

Purpose: Estimation of Cerenkov dose from high-energy megavoltage photon and electron beams in tissue and its impact on the radiosensitization using Protoporphyrine IX (PpIX) for tumor targeting enhancement in radiotherapy. Methods: The GEPTS Monte Carlo code is used to generate dose distributions from 18MV Varian photon beam and generic high-energy (45-MV) photon and (45-MeV) electron beams in a voxel-based tissueequivalent phantom. In addition to calculating the ionization dose, the code scores Cerenkov energy released in the wavelength range 375–425 nm corresponding to the pick of the PpIX absorption spectrum (Fig. 1) using the Frank-Tamm formula. Results: The simulations shows thatmore » the produced Cerenkov dose suitable for activating PpIX is 4000 to 5500 times lower than the overall radiation dose for all considered beams (18MV, 45 MV and 45 MeV). These results were contradictory to the recent experimental studies by Axelsson et al. (Med. Phys. 38 (2011) p 4127), where Cerenkov dose was reported to be only two orders of magnitude lower than the radiation dose. Note that our simulation results can be corroborated by a simple model where the Frank and Tamm formula is applied for electrons with 2 MeV/cm stopping power generating Cerenkov photons in the 375–425 nm range and assuming these photons have less than 1mm penetration in tissue. Conclusion: The Cerenkov dose generated by high-energy photon and electron beams may produce minimal clinical effect in comparison with the photon fluence (or dose) commonly used for photo-dynamic therapy. At the present time, it is unclear whether Cerenkov radiation is a significant contributor to the recently observed tumor regression for patients receiving radiotherapy and PpIX versus patients receiving radiotherapy only. The ongoing study will include animal experimentation and investigation of dose rate effects on PpIX response.« less

Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring.

PubMed

Avci, Pinar; Gupta, Asheesh; Sadasivam, Magesh; Vecchio, Daniela; Pam, Zeev; Pam, Nadav; Hamblin, Michael R

2013-03-01

Low-level laser (light) therapy (LLLT) is a fast-growing technology used to treat a multitude of conditions that require stimulation of healing, relief of pain and inflammation, and restoration of function. Although skin is naturally exposed to light more than any other organ, it still responds well to red and near-infrared wavelengths. The photons are absorbed by mitochondrial chromophores in skin cells. Consequently, electron transport, adenosine triphosphate nitric oxide release, blood flow, reactive oxygen species increase, and diverse signaling pathways are activated. Stem cells can be activated, allowing increased tissue repair and healing. In dermatology, LLLT has beneficial effects on wrinkles, acne scars, hypertrophic scars, and healing of burns. LLLT can reduce UV damage both as a treatment and as a prophylactic measure. In pigmentary disorders such as vitiligo, LLLT can increase pigmentation by stimulating melanocyte proliferation and reduce depigmentation by inhibiting autoimmunity. Inflammatory diseases such as psoriasis and acne can also be managed. The noninvasive nature and almost complete absence of side effects encourage further testing in dermatology.

If I had a magic wand....Wish list of a dermatologist (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kelly, Kristen M.

2016-02-01

Challenges in dermatology that can be addressed by photonics research will be explored. Non-invasive, real-time diagnosis of skin lesions would eliminate biopsy risks, minimize patient anxiety by providing more rapid answers and allow diagnosis and treatment in a single visit. Multiple approaches have been tried, but significant limitations of current technologies make them impractical for routine clinic implementation. Photonics can also be used for treatment assessment to determine if intervention is adequate or if further treatment is needed. Ideal feedback should be non-invasive, rapid and accurate. Monitoring for potential adverse effects can greatly improve treatment safety, allowing clinicians to push the limits of therapy while preventing serious complications. Light based therapies can also be improved by increasing photon penetration and selectivity for targeted cells or skin structures. Current light based treatments are in many cases limited by photon penetration. In addition, we often seek to damage a specific chromophore but are not able to distinguish between targeted disease and non-targeted normal structures such as the cells of a melanoma and normal melanocytes and port wine stain versus normal vasculature. Scientist and clinician collaboration can address these and other issues and greatly improve patient care.

Active Detection of Shielded Special Nuclear Material in the Presence of Variable High Backgrounds Using a Mixed Photon-Neutron Source

NASA Astrophysics Data System (ADS)

Martin, Philip N.; Clemett, Ceri D.; Hill, Cassie; O'Malley, John; Campbell, Ben

This paper describes and compares two approaches to the analysis of active interrogation data containing high photon backgrounds associated with mixed photon-neutron source flash active interrogation. Results from liquid scintillation detectors (EJ301/EJ309) fielded at the Naval Research Laboratory (NRL), in collaboration with the Atomic Weapons Establishment (AWE), using the NRL Mercury Inductive Voltage Adder (IVA) operating in both a photon and mixed photon-neutron mode at a Depleted Uranium (DU) target are presented. The standard approach applying a Figure of Merit (FOM) consisting of background sigma above background is compared with an approach looking to fit only the time-decaying photon signal with standard delayed photon emission from ∼10-MeV end-point-energy Bremsstrahlung photofission of DU. Examples where each approach does well and less well are presented together with a discussion of the relative limitations of both approaches to the type of mixed photon-neutron flash active interrogation being considered.

Some computer graphical user interfaces in radiation therapy

PubMed Central

Chow, James C L

2016-01-01

In this review, five graphical user interfaces (GUIs) used in radiation therapy practices and researches are introduced. They are: (1) the treatment time calculator, superficial X-ray treatment time calculator (SUPCALC) used in the superficial X-ray radiation therapy; (2) the monitor unit calculator, electron monitor unit calculator (EMUC) used in the electron radiation therapy; (3) the multileaf collimator machine file creator, sliding window intensity modulated radiotherapy (SWIMRT) used in generating fluence map for research and quality assurance in intensity modulated radiation therapy; (4) the treatment planning system, DOSCTP used in the calculation of 3D dose distribution using Monte Carlo simulation; and (5) the monitor unit calculator, photon beam monitor unit calculator (PMUC) used in photon beam radiation therapy. One common issue of these GUIs is that all user-friendly interfaces are linked to complex formulas and algorithms based on various theories, which do not have to be understood and noted by the user. In that case, user only needs to input the required information with help from graphical elements in order to produce desired results. SUPCALC is a superficial radiation treatment time calculator using the GUI technique to provide a convenient way for radiation therapist to calculate the treatment time, and keep a record for the skin cancer patient. EMUC is an electron monitor unit calculator for electron radiation therapy. Instead of doing hand calculation according to pre-determined dosimetric tables, clinical user needs only to input the required drawing of electron field in computer graphical file format, prescription dose, and beam parameters to EMUC to calculate the required monitor unit for the electron beam treatment. EMUC is based on a semi-experimental theory of sector-integration algorithm. SWIMRT is a multileaf collimator machine file creator to generate a fluence map produced by a medical linear accelerator. This machine file controls the multileaf collimator to deliver intensity modulated beams for a specific fluence map used in quality assurance or research. DOSCTP is a treatment planning system using the computed tomography images. Radiation beams (photon or electron) with different energies and field sizes produced by a linear accelerator can be placed in different positions to irradiate the tumour in the patient. DOSCTP is linked to a Monte Carlo simulation engine using the EGSnrc-based code, so that 3D dose distribution can be determined accurately for radiation therapy. Moreover, DOSCTP can be used for treatment planning of patient or small animal. PMUC is a GUI for calculation of the monitor unit based on the prescription dose of patient in photon beam radiation therapy. The calculation is based on dose corrections in changes of photon beam energy, treatment depth, field size, jaw position, beam axis, treatment distance and beam modifiers. All GUIs mentioned in this review were written either by the Microsoft Visual Basic.net or a MATLAB GUI development tool called GUIDE. In addition, all GUIs were verified and tested using measurements to ensure their accuracies were up to clinical acceptable levels for implementations. PMID:27027225

Decision analytic modeling for the economic analysis of proton radiotherapy for non-small cell lung cancer

PubMed Central

Richard, Patrick J.; Zeng, Jing; Apisarnthanarax, Smith; Rengan, Ramesh; Phillips, Mark H.

2018-01-01

Background Although proton radiation treatments are more costly than photon/X-ray therapy, they may lower overall treatment costs through reducing rates of severe toxicities and the costly management of those toxicities. To study this issue, we created a decision-model comparing proton vs. X-ray radiotherapy for locally advanced non-small cell lung cancer patients. Methods An influence diagram was created to model for radiation delivery, associated 6-month pneumonitis/esophagitis rates, and overall costs (radiation plus toxicity costs). Pneumonitis (age, chemo type, V20, MLD) and esophagitis (V60) predictors were modeled to impact toxicity rates. We performed toxicity-adjusted, rate-adjusted, risk group-adjusted, and radiosensitivity analyses. Results Upfront proton treatment costs exceeded that of photons [$16,730.37 (3DCRT), $23,893.83 (IMRT), $41,061.80 (protons)]. Based upon expected population pneumonitis and esophagitis rates for each modality, protons would be expected to recover $1,065.62 and $1,139.63 of the cost difference compared to 3DCRT or IMRT. For patients treated with IMRT experiencing grade 4 pneumonitis or grade 4 esophagitis, costs exceeded patients treated with protons without this toxicity. 3DCRT patients with grade 4 esophagitis had higher costs than proton patients without this toxicity. For the risk group analysis, high risk patients (age >65, carboplatin/paclitaxel) benefited more from proton therapy. A biomarker may allow patient selection for proton therapy, although the AUC alone is not sufficient to determine if the biomarker is clinically useful. Conclusions The comparison between proton and photon/X-ray radiation therapy for NSCLC needs to consider both the up-front cost of treatment and the possible long term cost of complications. In our analysis, current costs favor X-ray therapy. However, relatively small reductions in the cost of proton therapy may result in a shift to the preference for proton therapy.

SU-E-T-132: Assess the Shielding of Secondary Neutrons From Patient Collimator in Proton Therapy Considering Secondary Photons Generated in the Shielding Process with Monte Carlo Simulation

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

Yamanaka, M; Takashina, M; Kurosu, K

Purpose: In this study we present Monte Carlo based evaluation of the shielding effect for secondary neutrons from patient collimator, and secondary photons emitted in the process of neutron shielding by combination of moderator and boron-10 placed around patient collimator. Methods: The PHITS Monte Carlo Simulation radiation transport code was used to simulate the proton beam (Ep = 64 to 93 MeV) from a proton therapy facility. In this study, moderators (water, polyethylene and paraffin) and boron (pure {sup 10}B) were placed around patient collimator in this order. The rate of moderator and boron thicknesses was changed fixing the totalmore » thickness at 3cm. The secondary neutron and photons doses were evaluated as the ambient dose equivalent per absorbed dose [H*(10)/D]. Results: The secondary neutrons are shielded more effectively by combination moderators and boron. The most effective combination of shielding neutrons is the polyethylene of 2.4 cm thick and the boron of 0.6 cm thick and the maximum reduction rate is 47.3 %. The H*(10)/D of secondary photons in the control case is less than that of neutrons by two orders of magnitude and the maximum increase of secondary photons is 1.0 µSv/Gy with the polyethylene of 2.8 cm thick and the boron of 0.2 cm thick. Conclusion: The combination of moderators and boron is beneficial for shielding secondary neutrons. Both the secondary photons of control and those emitted in the shielding neutrons are very lower than the secondary neutrons and photon has low RBE in comparison with neutron. Therefore the secondary photons can be ignored in the shielding neutrons.This work was supported by JSPS Core-to-Core Program (No.23003). This work was supported by JSPS Core-to-Core Program (No.23003)« less

Long-term cosmetic outcomes and toxicities of proton beam therapy compared with photon-based 3-dimensional conformal accelerated partial-breast irradiation: a phase 1 trial.

PubMed

Galland-Girodet, Sigolène; Pashtan, Itai; MacDonald, Shannon M; Ancukiewicz, Marek; Hirsch, Ariel E; Kachnic, Lisa A; Specht, Michelle; Gadd, Michele; Smith, Barbara L; Powell, Simon N; Recht, Abram; Taghian, Alphonse G

2014-11-01

To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

A new concept of pencil beam dose calculation for 40-200 keV photons using analytical dose kernels.

PubMed

Bartzsch, Stefan; Oelfke, Uwe

2013-11-01

The advent of widespread kV-cone beam computer tomography in image guided radiation therapy and special therapeutic application of keV photons, e.g., in microbeam radiation therapy (MRT) require accurate and fast dose calculations for photon beams with energies between 40 and 200 keV. Multiple photon scattering originating from Compton scattering and the strong dependence of the photoelectric cross section on the atomic number of the interacting tissue render these dose calculations by far more challenging than the ones established for corresponding MeV beams. That is why so far developed analytical models of kV photon dose calculations fail to provide the required accuracy and one has to rely on time consuming Monte Carlo simulation techniques. In this paper, the authors introduce a novel analytical approach for kV photon dose calculations with an accuracy that is almost comparable to the one of Monte Carlo simulations. First, analytical point dose and pencil beam kernels are derived for homogeneous media and compared to Monte Carlo simulations performed with the Geant4 toolkit. The dose contributions are systematically separated into contributions from the relevant orders of multiple photon scattering. Moreover, approximate scaling laws for the extension of the algorithm to inhomogeneous media are derived. The comparison of the analytically derived dose kernels in water showed an excellent agreement with the Monte Carlo method. Calculated values deviate less than 5% from Monte Carlo derived dose values, for doses above 1% of the maximum dose. The analytical structure of the kernels allows adaption to arbitrary materials and photon spectra in the given energy range of 40-200 keV. The presented analytical methods can be employed in a fast treatment planning system for MRT. In convolution based algorithms dose calculation times can be reduced to a few minutes.

Characterization of Compton-scatter imaging with an analytical simulation method

PubMed Central

Jones, Kevin C; Redler, Gage; Templeton, Alistair; Bernard, Damian; Turian, Julius V; Chu, James C H

2018-01-01

By collimating the photons scattered when a megavoltage therapy beam interacts with the patient, a Compton-scatter image may be formed without the delivery of an extra dose. To characterize and assess the potential of the technique, an analytical model for simulating scatter images was developed and validated against Monte Carlo (MC). For three phantoms, the scatter images collected during irradiation with a 6 MV flattening-filter-free therapy beam were simulated. Images, profiles, and spectra were compared for different phantoms and different irradiation angles. The proposed analytical method simulates accurate scatter images up to 1000 times faster than MC. Minor differences between MC and analytical simulated images are attributed to limitations in the isotropic superposition/convolution algorithm used to analytically model multiple-order scattering. For a detector placed at 90° relative to the treatment beam, the simulated scattered photon energy spectrum peaks at 140–220 keV, and 40–50% of the photons are the result of multiple scattering. The high energy photons originate at the beam entrance. Increasing the angle between source and detector increases the average energy of the collected photons and decreases the relative contribution of multiple scattered photons. Multiple scattered photons cause blurring in the image. For an ideal 5 mm diameter pinhole collimator placed 18.5 cm from the isocenter, 10 cGy of deposited dose (2 Hz imaging rate for 1200 MU min−1 treatment delivery) is expected to generate an average 1000 photons per mm2 at the detector. For the considered lung tumor CT phantom, the contrast is high enough to clearly identify the lung tumor in the scatter image. Increasing the treatment beam size perpendicular to the detector plane decreases the contrast, although the scatter subject contrast is expected to be greater than the megavoltage transmission image contrast. With the analytical method, real-time tumor tracking may be possible through comparison of simulated and acquired patient images. PMID:29243663

Characterization of Compton-scatter imaging with an analytical simulation method

NASA Astrophysics Data System (ADS)

Jones, Kevin C.; Redler, Gage; Templeton, Alistair; Bernard, Damian; Turian, Julius V.; Chu, James C. H.

2018-01-01

By collimating the photons scattered when a megavoltage therapy beam interacts with the patient, a Compton-scatter image may be formed without the delivery of an extra dose. To characterize and assess the potential of the technique, an analytical model for simulating scatter images was developed and validated against Monte Carlo (MC). For three phantoms, the scatter images collected during irradiation with a 6 MV flattening-filter-free therapy beam were simulated. Images, profiles, and spectra were compared for different phantoms and different irradiation angles. The proposed analytical method simulates accurate scatter images up to 1000 times faster than MC. Minor differences between MC and analytical simulated images are attributed to limitations in the isotropic superposition/convolution algorithm used to analytically model multiple-order scattering. For a detector placed at 90° relative to the treatment beam, the simulated scattered photon energy spectrum peaks at 140-220 keV, and 40-50% of the photons are the result of multiple scattering. The high energy photons originate at the beam entrance. Increasing the angle between source and detector increases the average energy of the collected photons and decreases the relative contribution of multiple scattered photons. Multiple scattered photons cause blurring in the image. For an ideal 5 mm diameter pinhole collimator placed 18.5 cm from the isocenter, 10 cGy of deposited dose (2 Hz imaging rate for 1200 MU min-1 treatment delivery) is expected to generate an average 1000 photons per mm2 at the detector. For the considered lung tumor CT phantom, the contrast is high enough to clearly identify the lung tumor in the scatter image. Increasing the treatment beam size perpendicular to the detector plane decreases the contrast, although the scatter subject contrast is expected to be greater than the megavoltage transmission image contrast. With the analytical method, real-time tumor tracking may be possible through comparison of simulated and acquired patient images.

SPECT/CT localization of oral radioiodine activity: a retrospective study and in-vitro assessment

PubMed Central

Burlison, Jared S.; Hartshorne, Michael F.; Voda, Alan M.; Cocks, Franklin H.

2013-01-01

Purpose We sought to further localize radioiodine activity in the mouth on post-thyroid cancer therapy imaging using single-photon emission computed tomography/computed tomography (SPECT/CT). Materials and methods We retrospectively reviewed all patients (58) who underwent thyroid cancer therapy with iodine-131 (131I) at our institution from August 2009 to March 2011 whose post-therapy radioiodine imaging included neck SPECT/CT. A small group (six) of diagnostic 123I scans including SPECT/CT was also reviewed. Separately, we performed in-vitro 131I (sodium iodide) binding assays with amalgam and Argenco HP 77 (77% dental gold alloy) as proof of principle for these interactions. Results Of the 58 post-therapy patients, 45 (78%) had undergone metallic dental restorations, and of them 41 (91%) demonstrated oral 131I activity localizing preferentially to those restorations. It was observed that radioiodine also localized to other dental restorations and to orthodontic hardware. Gum-line activity in edentulous patients suggests radioiodine interaction with denture adhesive. In vitro, dental amalgam and Argenco HP 77 bound 131I in a time-dependent manner over 1–16 days of exposure. Despite subsequent washings with normal saline, significant 131I activity (maximally 12% for amalgam and 68% for Argenco HP 77) was retained by these metals. Subsequent soaking in a saturated solution of potassium iodide partially displaced 131I from amalgam, with near-total displacement of 131I from Argenco HP 77. Conclusion SPECT/CT shows that radioiodine in the oral cavity localizes to metallic dental restorations. Furthermore, in-vitro studies demonstrate partially reversible binding of 131I to common dental metals. PMID:24128897

Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST).

PubMed

Chahine, George; Short, Baron; Spicer, Ken; Schmidt, Matthew; Burns, Carol; Atoui, Mia; George, Mark S; Sackeim, Harold A; Nahas, Ziad

2014-01-01

Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. Copyright © 2014 Elsevier Inc. All rights reserved.

Radiotherapy and risk of implantable cardioverter-defibrillator malfunctions: experimental data from direct exposure at increasing doses.

PubMed

Zecchin, Massimo; Artico, Jessica; Morea, Gaetano; Severgnini, Mara; Bianco, Elisabetta; De Luca, Antonio; Fantasia, Anna Zorzin; Salvatore, Luca; Milan, Vittorino; Lucarelli, Matteo; Dissegna, Roberta; Cannatà, Antonio; Sinagra, Gianfranco

2018-04-01

During radiotherapy, in patients with implantable cardioverter-defibrillators (ICDs) malfunctions are considered more likely if doses more than 2 Gy reach the ICD site; however, most malfunctions occur with high-energy (>10 MV) radiations, and the risk is less defined using 6-MV linear accelerators. The purpose of the study is to experimentally evaluate the occurrence of malfunctions in ICDs radiated with a 6-MV linear accelerator at increasing photon doses. Thirty-two ICDs from all manufacturers (31 explanted and one demo) were evaluated; all devices with a sufficient battery charge underwent multiple radiations with a 6-MV photon beam reaching a cumulative dose at ICD site of 0.5, 1, 2, 3, 5 and 10 Gy and interrogated after every session. All antitachycardia therapies were left enabled; two ICDs were connected to a rhythm simulator (one simulating a complete atrioventricular block without ventricular activity) and visually monitored by external ECG and the ICD programmer during radiation. Thirteen ICDs were excluded before radiation because of battery depletion; after radiation up to the cumulative dose at the cardiac implantable electronic device site of 10 Gy, in the remaining 19 devices, programmation and battery charge remained unchanged and no switch to safety mode was observed; oversensing, pacing inhibition or inappropriate antitachycardia therapy were neither recorded nor visually observed during radiation. With a low-energy accelerator, neither malfunctions nor electromagnetic interferences were detected radiating the ICDs at doses usually reaching the ICD pocket during radiotherapy sessions. In this context, magnet application to avoid oversensing and inappropriate therapy seems, therefore, useless.

Nanoparticle-enhanced x-ray therapy for cancer

NASA Astrophysics Data System (ADS)

Letfullin, Renat R.; Rice, Colin E. W.; George, Thomas F.

2016-03-01

Photothermal therapies of nanophotohyperthermia and nanophotothermolysis utilize the light absorptive properties of nanoparticles to create heat and free radicals in a small localized region. Conjugating nanoparticles with various biomolecules allows for targeted delivery to specific tissues or even specific cells, cancerous cells being of particular interest. Previous studies have investigated nanoparticles at visible and infrared wavelengths where surface plasmon resonance leads to unique absorption characteristics. However, issues such as poor penetration depth of the visible light through biological tissues limits the effectiveness of delivery by noninvasive means. In other news, various nanoparticles have been investigated as contrast agents for traditional X-ray procedures, utilizing the strong absorption characteristics of the nanoparticles to enhance contrast of the detected X-ray image. Using X-rays to power photothermal therapies has three main advantages over visiblespectra wavelengths: the high penetration depth of X-rays through biological media makes noninvasive treatments very feasible; the high energy of individual photons means nanoparticles can be heated to desired temperatures with lower beam intensities, or activated to produce the free radicals; and X-ray sources are already common throughout the medical industry, making future implementation on existing equipment possible. This paper uses Lorenz-Mie theory to investigate the light absorption properties of various size gold nanoparticles over photon energies in the 1-100 keV range. These absorption values are then plugged into a thermal model to determine the temperatures reached by the nanoparticles for X-ray exposures of differing time and intensity. The results of these simulations are discussed in relation to the effective implementation of nanophotohyperthermia and nanophotothermolysis treatments.

Synthesis and photonic property study of ZnO nanowires for a real time photodynamic therapy monitoring probe

NASA Astrophysics Data System (ADS)

Sridhar, D.; Xie, Jining; Abraham, Jose K.; Varadan, Vijay K.

2007-04-01

In this paper, we present how the photonic properties of zinc oxide (ZnO) nanowires can be used to potentially advance the effectiveness of Photodynamic therapy (PDT), one of the most recent and promising approaches among cancer therapies. Presently, PDT employs laser light to activate intravenously or topically administered photosensitizers to give rise to highly reactive singlet oxygen which has a very short lifetime and is capable of biochemical damage to cell membranes of the tumor. A probe that can monitor in real time the penetration depth of the laser in the tumor and also the evolution of the singlet oxygen, which is critical for tumor eradication, is capable of improving the efficacy of PDT quite significantly. Such a probe, by providing real time feedback, can help us determine whether to increase or decrease the light exposure dose and also if further local administration of photosensitizers is required or not. ZnO nanowires are known to be photoconductive and recent research also demonstrated the temperature dependence of the photocurrent in the nanowires. They are also sensitive to blue and other near UV spectra which is same range of activation wavelengths of most photosensitizers, and hence making them a good candidate for a potential PDT monitoring probe. ZnO nanowires were fabricated on silicon substrates by vapor phase deposition using e-beam evaporated gold as a catalyst. Control of the dimensions of the nanowires could be achieved by varying the dimensions of the catalyst by means of e-beam evaporation process. Photoluminescence properties of ZnO nanowires were investigated at UV and near UV wavelengths. Further, ZnO is also known for its antimicrobial properties, thereby ruling out any possibility of bacterial infection because of the implanted probe. This study was done to compliment the existing expertise of our research group in the design and fabrication of several nanowire based probes and microsensors specifically for neuroelectronic and nanomedicine applications.

Regenerative photonic therapy: Review

NASA Astrophysics Data System (ADS)

Salansky, Natasha; Salansky, Norman

2012-09-01

After four decades of research of photobiomodulation phenomena in mammals in vitro and in vivo, a solid foundation is created for the use of photobiomodulation in regenerative medicine. Significant accomplishments are achieved in animal models that demonstrate opportunities for photo-regeneration of injured or pathological tissues: skin, muscles and nerves. However, the use of photobiomodulation in clinical studies leads to controversial results while negative or marginal clinical efficacy is reported along with positive findings. A thor ough analysis of requirements to the optical parameters (dosimetry) for high efficacy in photobimodulation led us to the conclusion that there are several misconceptions in the clinical applications of low level laser therapy (LLLT). We present a novel appr oach of regenerative photonic therapy (RPT) for tissue healing and regeneration that overcomes major drawbacks of LLLT. Encouraging clinical results on RPT efficacy are presented. Requirements for RPT approach and vision for its future development for tissue regeneration is discussed.

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

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

Chuong, Michael D.; Hallemeier, Christopher L.; Jabbour, Salma K.

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with protonmore » beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.« less

Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

PubMed

Chuong, Michael D; Hallemeier, Christopher L; Jabbour, Salma K; Yu, Jen; Badiyan, Shahed; Merrell, Kenneth W; Mishra, Mark V; Li, Heng; Verma, Vivek; Lin, Steven H

2016-05-01

Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT. Copyright © 2016 Elsevier Inc. All rights reserved.

Ultrafast studies of the excited-state dynamics of copper and nickel phthalocyanine tetrasulfonates: potential sensitizers for the two-photon photodynamic therapy of tumors.

PubMed

Fournier, Michel; Pépin, Claude; Houde, Daniel; Ouellet, René; van Lier, Johan E

2004-01-01

In order to evaluate the potential of copper and nickel phthalocyanine tetrasulfonates as sensitizers for two-photon photodynamic therapy, we conducted kinetic femtosecond measurements of transient absorption and bleaching of their excited state dynamics in aqueous solution. Samples were pumped with 620 nm and 310 nm laser light, which allowed us to study relaxation processes from both the first and second singlet (or doublet for the copper phthalocyanine) excited states. A second excitation from the first excited triplet state, approximately 685 and 105 ps after the first excitation for copper and nickel phthalocyanine tetrasulfonate respectively, was the most efficient way to bring the molecules to an upper triplet state. Presumably this highest triplet state can inflict molecular damage on adjacent biomolecules int eh absence of oxygen, resulting in the desired cytotoxic cellular response. Transient absorption spectra at different fixed delays indicate that optimum efficiency would require that the second photon has a wavelength of approximately 750 nm.

Nanoimprinted High-Refractive Index Active Photonic Nanostructures Based on Quantum Dots for Visible Light

DOE PAGES

Pina-Hernandez, Carlos; Koshelev, Alexander; Dhuey, Scott; ...

2017-12-15

A novel method to realizing printed active photonic devices was developed using nanoimprint lithography (NIL), combining a printable high-refractive index material and colloidal CdSe/CdS quantum dots (QDs) for applications in the visible region. Active media QDs were applied in two different ways: embedded inside a printable high-refractive index matrix to form an active printable hybrid nanocomposite, and used as a uniform coating on top of printed photonic devices. As a proof-of-demonstration for printed active photonic devices, two-dimensional (2-D) photonic crystals as well as 1D and 2D photonic nanocavities were successfully fabricated following a simple reverse-nanoimprint process. We observed enhanced photoluminescencemore » from the 2D photonic crystal and the 1D nanocavities. Outstandingly, the process presented in this study is fully compatible with large-scale manufacturing where the patterning areas are only limited by the size of the corresponding mold. This work shows that the integration of active media and functional materials is a promising approach to the realization of integrated photonics for visible light using high throughput technologies. We believe that this work represents a powerful and cost-effective route for the development of numerous nanophotonic structures and devices that will lead to the emergence of new applications.« less

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.

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

Respiratory gating for proton beam scanning versus photon 3D-CRT for breast cancer radiotherapy.

PubMed

Flejmer, Anna M; Edvardsson, Anneli; Dohlmar, Frida; Josefsson, Dan; Nilsson, Mats; Witt Nyström, Petra; Dasu, Alexandru

2016-05-01

Background Respiratory gating and proton therapy have both been proposed to reduce the cardiopulmonary burden in breast cancer radiotherapy. This study aims to investigate the additional benefit of proton radiotherapy for breast cancer with and without respiratory gating. Material and methods Twenty left-sided patients were planned on computed tomography (CT)-datasets acquired during enhanced inspiration gating (EIG) and free-breathing (FB), using photon three-dimensional conformal radiation therapy (3D-CRT) and scanned proton beams. Ten patients received treatment to the whole breast only (WBO) and 10 were treated to the breast and the regional lymph nodes (BRN). Dosimetric parameters characterizing the coverage of target volumes and the cardiopulmonary burden were compared using a paired, two-tailed Student's t-test. Results Protons ensured comparable or better target coverage than photons in all patients during both EIG and FB. The heterogeneity index decreased from 12% with photons to about 5% with protons. The mean dose to the ipsilateral lung was reduced in BRN patients from 12 Gy to 7 Gy  (RBE) in EIG and from 14 Gy to 6-7 Gy (RBE) in FB, while for WBO patients all values were about 5-6 Gy (RBE). The mean dose to heart decreased by a factor of four in WBO patients [from 1.1 Gy to 0.3 Gy (RBE) in EIG and from 2.1 Gy to 0.5 Gy (RBE) in FB] and 10 in BRN patients [from 2.1 Gy to 0.2 Gy (RBE) in EIG and from 3.4 Gy to 0.3 Gy (RBE) in FB]. Similarly, the mean and the near maximum dose to the left anterior descending artery (LAD) were significantly lower (p < 0.05) with protons in comparison with photons. Conclusion Proton spot scanning has a high potential to reduce the irradiation of organs at risk and other normal tissues for most patients, beyond what could be achieved with EIG and photon therapy. The largest dose sparing has been seen for BRN patients, both in terms of cardiopulmonary burden and integral dose.

Using a knowledge-based planning solution to select patients for proton therapy.

PubMed

Delaney, Alexander R; Dahele, Max; Tol, Jim P; Kuijper, Ingrid T; Slotman, Ben J; Verbakel, Wilko F A R

2017-08-01

Patient selection for proton therapy by comparing proton/photon treatment plans is time-consuming and prone to bias. RapidPlan™, a knowledge-based-planning solution, uses plan-libraries to model and predict organ-at-risk (OAR) dose-volume-histograms (DVHs). We investigated whether RapidPlan, utilizing an algorithm based only on photon beam characteristics, could generate proton DVH-predictions and whether these could correctly identify patients for proton therapy. Model PROT and Model PHOT comprised 30 head-and-neck cancer proton and photon plans, respectively. Proton and photon knowledge-based-plans (KBPs) were made for ten evaluation-patients. DVH-prediction accuracy was analyzed by comparing predicted-vs-achieved mean OAR doses. KBPs and manual plans were compared using salivary gland and swallowing muscle mean doses. For illustration, patients were selected for protons if predicted Model PHOT mean dose minus predicted Model PROT mean dose (ΔPrediction) for combined OARs was ≥6Gy, and benchmarked using achieved KBP doses. Achieved and predicted Model PROT /Model PHOT mean dose R 2 was 0.95/0.98. Generally, achieved mean dose for Model PHOT /Model PROT KBPs was respectively lower/higher than predicted. Comparing Model PROT /Model PHOT KBPs with manual plans, salivary and swallowing mean doses increased/decreased by <2Gy, on average. ΔPrediction≥6Gy correctly selected 4 of 5 patients for protons. Knowledge-based DVH-predictions can provide efficient, patient-specific selection for protons. A proton-specific RapidPlan-solution could improve results. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

An analytical method for computing voxel S values for electrons and photons.

PubMed

Amato, Ernesto; Minutoli, Fabio; Pacilio, Massimiliano; Campenni, Alfredo; Baldari, Sergio

2012-11-01

The use of voxel S values (VSVs) is perhaps the most common approach to radiation dosimetry for nonuniform distributions of activity within organs or tumors. However, VSVs are currently available only for a limited number of voxel sizes and radionuclides. The objective of this study was to develop a general method to evaluate them for any spectrum of electrons and photons in any cubic voxel dimension of practical interest for clinical dosimetry in targeted radionuclide therapy. The authors developed a Monte Carlo simulation in Geant4 in order to evaluate the energy deposited per disintegration (E(dep)) in a voxelized region of soft tissue from monoenergetic electrons (10-2000 keV) or photons (10-1000 keV) homogeneously distributed in the central voxel, considering voxel dimensions ranging from 3 mm to 10 mm. E(dep) was represented as a function of a dimensionless quantity termed the "normalized radius," R(n) = R∕l, where l is the voxel size and R is the distance from the origin. The authors introduced two parametric functions in order to fit the electron and photon results, and they interpolated the parameters to derive VSVs for any energy and voxel side within the ranges mentioned above. In order to validate the results, the authors determined VSV for two radionuclides ((131)I and (89)Sr) and two voxel dimensions and they compared them with reference data. A validation study in a simple sphere model, accounting for tissue inhomogeneities, is presented. The E(dep)(R(n)) for both monoenergetic electrons and photons exhibit a smooth variation with energy and voxel size, implying that VSVs for monoenergetic electrons or photons may be derived by interpolation over the range of energies and dimensions considered. By integration, S values for continuous emission spectra from β(-) decay may be derived as well. The approach allows the determination of VSVs for monoenergetic (Auger or conversion) electrons and (x-ray or gamma-ray) photons by means of two functions whose parameters can be interpolated from tabular data provided. Through integration, it is possible to generalize the method to any continuous (beta) spectrum, allowing to calculate VSVs for any electron and photon emitter in a voxelized structure.

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

TOPICAL REVIEW: The physics, biophysics and technology of photodynamic therapy

NASA Astrophysics Data System (ADS)

Wilson, Brian C.; Patterson, Michael S.

2008-05-01

Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components—light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT.

Photoelectron Transfer at ZnTPyP Self-Assembly/TiO2 Interfaces for Enhanced Two-Photon Photodynamic Therapy.

PubMed

Liu, Yanyan; Meng, Xianfu; Wang, Han; Tang, Zhongmin; Zuo, Changjing; He, Mingyuan; Bu, Wenbo

2018-01-17

Two-photon (TP) absorption nanomaterials are highly desirable for deep-tissue clinical diagnostics and orthotopic disease treatment. Here, a well-designed core/shell nanostructure was successfully synthesized with a ZnTPyP self-assembly nanocrystal (ZSN) inner core coated by a homogeneous TiO 2 layer outside (ZSN-TO). The ZSN is a good photosemiconductor, showing both one-photon (OP) and TP absorption properties for red fluorescence emission and electron-hole pair generation; TiO 2 with good biocompatibility acts as the electron acceptor, which can transfer photoelectron from ZSN to TiO 2 for highly effective electron-hole separation, favoring the production of long-life superoxide anion (O 2 •- ) by electrons and oxygen and strong oxidizing hydroxyl radical (•OH) by holes and surrounding H 2 O. Once pretreated with ZSN-TO, the simultaneous OP-405 nm or TP-800 nm laser stimulation and fluorescent imaging of reactive oxygen species (ROS) showed dynamical and continuous generation of ROS in HeLa cells, with cytotoxicity significantly increasing via the type-1-like photodynamic therapy process. The results demonstrated that the combination of organic ZSN with inorganic TiO 2 has great applications as an excellent photosensitizer for deep-tissue fluorescent imaging and noninvasive disease treatment via TP photodynamic therapy.

Special cases for proton beam radiotherapy: re-irradiation, lymphoma, and breast cancer.

PubMed

Plastaras, John P; Berman, Abigail T; Freedman, Gary M

2014-12-01

The dose distributions that can be achieved with protons are usually superior to those of conventional photon external-beam radiation. There are special cases where proton therapy may offer a substantial potential benefit compared to photon treatments where toxicity concerns dominate. Re-irradiation may theoretically be made safer with proton therapy due to lower cumulative lifetime doses to sensitive tissues, such as the spinal cord. Proton therapy has been used in a limited number of patients with rectal, pancreatic, esophageal, and lung cancers. Chordomas and soft tissue sarcomas require particularly high radiation doses, posing additional challenges for re-irradiation. Lymphoma is another special case where proton therapy may be advantageous. Late toxicities from even relatively low radiation doses, including cardiac complications and second cancers, are of concern in lymphoma patients with high cure rates and long life expectancies. Proton therapy has begun to be used for consolidation after chemotherapy in patients with Hodgkin and non-Hodgkin lymphoma. Breast cancer is another emerging area of proton therapy development and use. Proton therapy may offer advantages compared to other techniques in the setting of breast boosts, accelerated partial breast irradiation, and post-mastectomy radiotherapy. In these settings, proton therapy may decrease toxicity associated with breast radiotherapy. As techniques are refined in proton therapy, we may be able to improve the therapeutic ratio by maintaining the benefits of radiotherapy while better minimizing the risks. Copyright © 2014 Elsevier Inc. All rights reserved.

Emerging technologies in Si active photonics

NASA Astrophysics Data System (ADS)

Wang, Xiaoxin; Liu, Jifeng

2018-06-01

Silicon photonics for synergistic electronic–photonic integration has achieved remarkable progress in the past two decades. Active photonic devices, including lasers, modulators, and photodetectors, are the key challenges for Si photonics to meet the requirement of high bandwidth and low power consumption in photonic datalinks. Here we review recent efforts and progress in high-performance active photonic devices on Si, focusing on emerging technologies beyond conventional foundry-ready Si photonics devices. For emerging laser sources, we will discuss recent progress towards efficient monolithic Ge lasers, mid-infrared GeSn lasers, and high-performance InAs quantum dot lasers on Si for data center applications in the near future. We will then review novel modulator materials and devices beyond the free carrier plasma dispersion effect in Si, including GeSi and graphene electro-absorption modulators and plasmonic-organic electro-optical modulators, to achieve ultralow power and high speed modulation. Finally, we discuss emerging photodetectors beyond epitaxial Ge p–i–n photodiodes, including GeSn mid-infrared photodetectors, all-Si plasmonic Schottky infrared photodetectors, and Si quanta image sensors for non-avalanche, low noise single photon detection and photon counting. These emerging technologies, though still under development, could make a significant impact on the future of large-scale electronicSilicon photonics for synergistic electronic-photonic integration has achieved remarkable progress in the past two decades. Active photonic devices, including lasers, modulators, and photodetectors, are the key challenges for Si photonics to meet the requirement of high bandwidth and low power consumption in photonic datalinks. Here we review recent efforts and progress in high-performance active photonic devices on Si, focusing on emerging technologies beyond conventional foundry-ready Si photonics devices. For emerging laser sources, we will discuss recent progress towards efficient monolithic Ge lasers, mid-infrared GeSn lasers, and high-performance InAs quantum dot lasers on Si for data center applications in the near future. We will then review novel modulator materials and devices beyond the free carrier plasma dispersion effect in Si, including GeSi and graphene electro-absorption modulators and plasmonic-organic electro–optical modulators, to achieve ultralow power and high speed modulation. Finally, we discuss emerging photodetectors beyond epitaxial Ge p–i–n photodiodes, including GeSn mid-infrared photodetectors, all-Si plasmonic Schottky infrared photodetectors, and Si quanta image sensors for non-avalanche, low noise single photon detection and photon counting. These emerging technologies, though still under development, could make a significant impact on the future of large-scale electronic–photonic integration with performance inaccessible from conventional Si photonics technologies-photonic integration with performance inaccessible from conventional Si photonics technologies.

New radiotherapeutic techniques in nuclear ophthalmology

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

Fairchild, R.G.

Various aspects of radiotherapeutic techniques used in treating ocular tumors are discussed. Previous and current ''standard'' modalities are briefly reviewed, including beta and gamma emitters, /sup 60/Co, /sup 125/I, and charged particles. In particular, emphasis is placed upon techniques under development that use biomolecules to physiologically target radioactive or stable isotopes to ocular melanoma. These procedures include /sup 35/S-thiouracil, /sup 127/I-deoxyuridine in conjunction with irradiation with photons from /sup 145/Sm, neutron capture therapy, and various combinations of the above. Thiouracil shows particular promise because of its incorporation during melanin synthesis in growing melanoma. Radiosensitization and stimulation of Auger cascades viamore » introduction of iodine in DNA followed by irradiation with activating photons of appropriate energy (from /sup 145/Sm) has been shown to be effective in vitro. Various molecules may be used to transport boron to ocular melanoma, including thiouracil, thus allowing selective irradiation of tumor cells via /sup 10/B (n, alpha) /sup 7/Li reaction.« less

A small-scale anatomical dosimetry model of the liver

NASA Astrophysics Data System (ADS)

Stenvall, Anna; Larsson, Erik; Strand, Sven-Erik; Jönsson, Bo-Anders

2014-07-01

Radionuclide therapy is a growing and promising approach for treating and prolonging the lives of patients with cancer. For therapies where high activities are administered, the liver can become a dose-limiting organ; often with a complex, non-uniform activity distribution and resulting non-uniform absorbed-dose distribution. This paper therefore presents a small-scale dosimetry model for various source-target combinations within the human liver microarchitecture. Using Monte Carlo simulations, Medical Internal Radiation Dose formalism-compatible specific absorbed fractions were calculated for monoenergetic electrons; photons; alpha particles; and 125I, 90Y, 211At, 99mTc, 111In, 177Lu, 131I and 18F. S values and the ratio of local absorbed dose to the whole-organ average absorbed dose was calculated, enabling a transformation of dosimetry calculations from macro- to microstructure level. For heterogeneous activity distributions, for example uptake in Kupffer cells of radionuclides emitting low-energy electrons (125I) or high-LET alpha particles (211At) the target absorbed dose for the part of the space of Disse, closest to the source, was more than eight- and five-fold the average absorbed dose to the liver, respectively. With the increasing interest in radionuclide therapy of the liver, the presented model is an applicable tool for small-scale liver dosimetry in order to study detailed dose-effect relationships in the liver.

[Why proton therapy? And how?

PubMed

Thariat, Juliette; Habrand, Jean Louis; Lesueur, Paul; Chaikh, Abdulhamid; Kammerer, Emmanuel; Lecomte, Delphine; Batalla, Alain; Balosso, Jacques; Tessonnier, Thomas

2018-03-01

Proton therapy is a radiotherapy, based on the use of protons, charged subatomic particles that stop at a given depth depending on their initial energy (pristine Bragg peak), avoiding any output beam, unlike the photons used in most of the other modalities of radiotherapy. Proton therapy has been used for 60 years, but has only become ubiquitous in the last decade because of recent major advances in particle accelerator technology. This article reviews the history of clinical implementation of protons, the nature of the technological advances that now allows its expansion at a lower cost. It also addresses the technical and physical specificities of proton therapy and the clinical situations for which proton therapy may be relevant but requires evidence. Different proton therapy techniques are possible. These are explained in terms of their clinical potential by explaining the current terminology (such as cyclotrons, synchrotrons or synchrocyclotrons, using superconducting magnets, fixed line or arm rotary with passive diffusion delivery or active by scanning) in basic words. The requirements associated with proton therapy are increased due to the precision of the depth dose deposit. The learning curve of proton therapy requires that clinical indications be prioritized according to their associated uncertainties (such as range uncertainties and movement in lung tumors). Many clinical indications potentially fall under proton therapy ultimately. Clinical strategies are explained in a paralleled manuscript. Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Energy optimization in gold nanoparticle enhanced radiation therapy.

PubMed

Sung, Wonmo; Schuemann, Jan

2018-06-25

Gold nanoparticles (GNPs) have been demonstrated as radiation dose enhancing agents. Kilovoltage external photon beams have been shown to yield the largest enhancement due to the high interaction probability with gold. While orthovoltage irradiations are feasible and promising, they suffer from a reduced tissue penetrating power. This study quantifies the effect of varying photon beam energies on various beam arrangements, body, tumor, and cellular GNP uptake geometries. Cell survival was modeled based on our previously developed GNP-local effect model with radial doses calculated using the TOPAS-nBio Monte Carlo code. Cell survival curves calculated for tumor sites with GNPs were used to calculate the relative biological effectiveness (RBE)-weighted dose. In order to evaluate the plan quality, the ratio of the mean dose between the tumor and normal tissue for 50-250 kVp beams with GNPs was compared to the standard of care using 6 MV photon beams without GNPs for breast and brain tumors. For breast using a single photon beam, kV  +  GNP was found to yield up to 2.73 times higher mean RBE-weighted dose to the tumor than two tangential megavoltage beams while delivering the same dose to healthy tissue. For irradiation of brain tumors using multiple photon beams, the GNP dose enhancement was found to be effective for energies above 50 keV. A small tumor at shallow depths was found to be the most effective treatment conditions for GNP enhanced radiation therapy. GNP uptake distributions in the cell (with or without nuclear uptake) and the beam arrangement were found to be important factors in determining the optimal photon beam energy.

Active temporal multiplexing of indistinguishable heralded single photons

PubMed Central

Xiong, C.; Zhang, X.; Liu, Z.; Collins, M. J.; Mahendra, A.; Helt, L. G.; Steel, M. J.; Choi, D. -Y.; Chae, C. J.; Leong, P. H. W.; Eggleton, B. J.

2016-01-01

It is a fundamental challenge in quantum optics to deterministically generate indistinguishable single photons through non-deterministic nonlinear optical processes, due to the intrinsic coupling of single- and multi-photon-generation probabilities in these processes. Actively multiplexing photons generated in many temporal modes can decouple these probabilities, but key issues are to minimize resource requirements to allow scalability, and to ensure indistinguishability of the generated photons. Here we demonstrate the multiplexing of photons from four temporal modes solely using fibre-integrated optics and off-the-shelf electronic components. We show a 100% enhancement to the single-photon output probability without introducing additional multi-photon noise. Photon indistinguishability is confirmed by a fourfold Hong–Ou–Mandel quantum interference with a 91±16% visibility after subtracting multi-photon noise due to high pump power. Our demonstration paves the way for scalable multiplexing of many non-deterministic photon sources to a single near-deterministic source, which will be of benefit to future quantum photonic technologies. PMID:26996317

SU-F-T-163: Improve Proton Therapy Efficiency: Report of a Workshop

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

Zheng, Y; Flanz, J; Mah, D

Purpose: The technology of proton therapy, especially the pencil beam scanning technique, is evolving very quickly. However, the efficiency of proton therapy seems to lag behind conventional photon therapy. The purpose of the abstract is to report on the findings of a workshop on improvement of QA, planning and treatment efficiency in proton therapy. Methods: A panel of physicists, clinicians, and vendor representatives from over 18 institutions in the United States and internationally were convened in Knoxville, Tennessee in November, 2015. The panel discussed several topics on how to improve proton therapy efficiency, including 1) lean principle and failure modemore » and effects analysis, 2) commissioning and machine QA, 3) treatment planning, optimization and evaluation, 4) patient positioning and IGRT, 5) vendor liaison and machine availability, and 6) staffing, education and training. Results: The relative time needed for machine QA, treatment planning & check in proton therapy was found to range from 1 to 2.5 times of that in photon therapy. Current status in proton QA, planning and treatment was assessed. Key areas for efficiency improvement, such as elimination of unnecessary QA items or steps and development of efficient software or hardware tools, were identified. A white paper to summarize our findings is being written. Conclusion: It is critical to improve efficiency by developing reliable proton beam lines, efficient software tools on treatment planning, optimization and evaluation, and dedicated proton QA device. Conscious efforts and collaborations from both industry leaders and proton therapy centers are needed to achieve this goal and further advance the technology of proton therapy.« less

Production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

PubMed

Melville, G; Meriarty, H; Metcalfe, P; Knittel, T; Allen, B J

2007-09-01

The increasing application of Ac-225 for cancer therapy indicates the potential need for its increased production and availability. The production of Ac-225 has been achieved using bremsstrahlung photons from an 18 MV medical linear accelerator (linac) to bombard a Ra-226 target. A linac dose of 2800 Gy produced about 64 microCi of Ra-225, which decays to Ac-225. This result, while consistent with the theoretical calculations, is far too low to be of practical use. A more powerful linac is required that runs at a higher current, longer pulse length and higher frequency for practical production. This process could also lead to the reduction of the nuclear waste product Ra-226.

Optimal moderator materials at various proton energies considering photon dose rate after irradiation for an accelerator-driven ⁹Be(p, n) boron neutron capture therapy neutron source.

PubMed

Hashimoto, Y; Hiraga, F; Kiyanagi, Y

2015-12-01

We evaluated the accelerator beam power and the neutron-induced radioactivity of (9)Be(p, n) boron neutron capture therapy (BNCT) neutron sources having a MgF2, CaF2, or AlF3 moderator and driven by protons with energy from 8 MeV to 30 MeV. The optimal moderator materials were found to be MgF2 for proton energies less than 10 MeV because of lower required accelerator beam power and CaF2 for higher proton energies because of lower photon dose rate at the treatment position after neutron irradiation. Copyright © 2015 Elsevier Ltd. All rights reserved.

In-situ second harmonic generation by cancer cell targeting ZnO nanocrystals to effect photodynamic action in subcellular space.

PubMed

Gu, Bobo; Pliss, Artem; Kuzmin, Andrey N; Baev, Alexander; Ohulchanskyy, Tymish Y; Damasco, Jossana A; Yong, Ken-Tye; Wen, Shuangchun; Prasad, Paras N

2016-10-01

This paper introduces the concept of in-situ upconversion of deep penetrating near infrared light via second harmonic generation from ZnO nanocrystals delivered into cells to effect photo activated therapies, such as photodynamic therapy, which usually require activation by visible light with limited penetration through biological tissues. We demonstrated this concept by subcellular activation of a photodynamic therapy drug, Chlorin e6, excited within its strong absorption Soret band by the second harmonic (SH) light, generated at 409 nm by ZnO nanocrystals, which were targeted to cancer cells and internalized through the folate-receptor mediated endocytosis. By a combination of theoretical modeling and experimental measurements, we show that SH light, generated in-situ by ZnO nanocrystals significantly contributes to activation of photosensitizer, leading to cell death through both apoptotic and necrotic pathways initiated in the cytoplasm. This targeted photodynamic action was studied using label-free Coherent Anti-Stokes Raman Scattering imaging of the treated cells to monitor changes in the distribution of native cellular proteins and lipids. We found that initiation of photodynamic therapy with upconverted light led to global reduction in the intracellular concentration of macromolecules, likely due to suppression of proteins and lipids synthesis, which could be considered as a real-time indicator of cellular damage from photodynamic treatment. In prospective applications this in-situ photon upconversion could be further extended using ZnO nanocrystals surface functionalized with a specific organelle targeting group, provided a powerful approach to identify and consequently maximize a cellular response to phototherapy, selectively initiated in a specific cellular organelle. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recommendations for the referral of patients for proton-beam therapy, an Alberta Health Services report: a model for Canada?

PubMed Central

Patel, S.; Kostaras, X.; Parliament, M.; Olivotto, I.A.; Nordal, R.; Aronyk, K.; Hagen, N.

2014-01-01

Background Compared with photon therapy, proton-beam therapy (pbt) offers compelling advantages in physical dose distribution. Worldwide, gantry-based proton facilities are increasing in number, but no such facilities exist in Canada. To access pbt, Canadian patients must travel abroad for treatment at high cost. In the face of limited access, this report seeks to provide recommendations for the selection of patients most likely to benefit from pbt and suggests an out-of-country referral process. Methods The medline, embase, PubMed, and Cochrane databases were systematically searched for studies published between January 1990 and May 2014 that evaluated clinical outcomes after pbt. A draft report developed through a review of evidence was externally reviewed and then approved by the Alberta Health Services Cancer Care Proton Therapy Guidelines steering committee. Results Proton therapy is often used to treat tumours close to radiosensitive tissues and to treat children at risk of developing significant late effects of radiation therapy (rt). In uncontrolled and retrospective studies, local control rates with pbt appear similar to, or in some cases higher than, photon rt. Randomized trials comparing equivalent doses of pbt and photon rt are not available. Summary Referral for pbt is recommended for patients who are being treated with curative intent and with an expectation for long-term survival, and who are able and willing to travel abroad to a proton facility. Commonly accepted indications for referral include chordoma and chondrosarcoma, intraocular melanoma, and solid tumours in children and adolescents who have the greatest risk for long-term sequelae. Current data do not provide sufficient evidence to recommend routine referral of patients with most head-and-neck, breast, lung, gastrointestinal tract, and pelvic cancers, including prostate cancer. It is recommended that all referrals be considered by a multidisciplinary team to select appropriate cases. PMID:25302033

Two-Photon Excitation in Biological Material for Conventional and Long Working-Distance Objectives.

NASA Astrophysics Data System (ADS)

Keeler, W. J.; McGhee, P.

2000-03-01

The application of laser two-photon excitation or nonlinear second-harmonic generation to imaging, spectroscopy, and light activated medical therapies, is an expanding field of research. When small feature sizes such as cells and their components are to be studied, high numerical aperture (NA) lenses are required to obtain the necessary lateral and axial resolutions. If one wishes to increase the depth of sample penetration, factors such as scattering and absorption quickly degrade the quality of the focused beam. The problem is further exacerbated by the short working distance of conventional high NA microscope objectives if they are used for light delivery and pickup. These lenses and their accompanying eyepieces, are designed to produce an exit pupil that can be accomodated by the human eye. Such a design will underfil detectors such as large CCD arrays. To simultaneously increase the working distance at the sample and the system exit pupil, larger scale objectives can be used. We will report the results of two-photon excitation and fluorescence investigations of several feature sizes as a function of penetration depth in homogeneous media and tissue samples, for conventional and long working distance objectives. The possible implications of these results to imaging and therapeutic dose delivery will also be presented.

Commissioning of intensity modulated neutron radiotherapy (IMNRT).

PubMed

Burmeister, Jay; Spink, Robyn; Liang, Liang; Bossenberger, Todd; Halford, Robert; Brandon, John; Delauter, Jonathan; Snyder, Michael

2013-02-01

Intensity modulated neutron radiotherapy (IMNRT) has been developed using inhouse treatment planning and delivery systems at the Karmanos Cancer Center∕Wayne State University Fast Neutron Therapy facility. The process of commissioning IMNRT for clinical use is presented here. Results of commissioning tests are provided including validation measurements using representative patient plans as well as those from the TG-119 test suite. IMNRT plans were created using the Varian Eclipse optimization algorithm and an inhouse planning system for calculation of neutron dose distributions. Tissue equivalent ionization chambers and an ionization chamber array were used for point dose and planar dose distribution comparisons with calculated values. Validation plans were delivered to water and virtual water phantoms using TG-119 measurement points and evaluation techniques. Photon and neutron doses were evaluated both inside and outside the target volume for a typical IMNRT plan to determine effects of intensity modulation on the photon dose component. Monitor unit linearity and effects of beam current and gantry angle on output were investigated, and an independent validation of neutron dosimetry was obtained. While IMNRT plan quality is superior to conventional fast neutron therapy plans for clinical sites such as prostate and head and neck, it is inferior to photon IMRT for most TG-119 planning goals, particularly for complex cases. This results significantly from current limitations on the number of segments. Measured and calculated doses for 11 representative plans (six prostate∕five head and neck) agreed to within -0.8 ± 1.4% and 5.0 ± 6.0% within and outside the target, respectively. Nearly all (22∕24) ion chamber point measurements in the two phantom arrangements were within the respective confidence intervals for the quantity [(measured-planned)∕prescription dose] derived in TG-119. Mean differences for all measurements were 0.5% (max = 7.0%) and 1.4% (max = 4.1%) in water and virtual water, respectively. The mean gamma pass rate for all cases was 92.8% (min = 88.6%). These pass rates are lower than typically achieved with photon IMRT, warranting development of a planar dosimetry system designed specifically for IMNRT and∕or the improvement of neutron beam modeling in the penumbral region. The fractional photon dose component did not change significantly in a typical IMNRT plan versus a conventional fast neutron therapy plan, and IMNRT delivery is not expected to significantly alter the RBE. All other commissioning results were considered satisfactory for clinical implementation of IMNRT, including the external neutron dose validation, which agreed with the predicted neutron dose to within 1%. IMNRT has been successfully commissioned for clinical use. While current plan quality is inferior to photon IMRT, it is superior to conventional fast neutron therapy. Ion chamber validation results for IMNRT commissioning are also comparable to those typically achieved with photon IMRT. Gamma pass rates for planar dose distributions are lower than typically observed for photon IMRT but may be improved with improved planar dosimetry equipment and beam modeling techniques. In the meantime, patient-specific quality assurance measurements should rely more heavily on point dose measurements with tissue equivalent ionization chambers. No significant technical impediments are anticipated in the clinical implementation of IMNRT as described here.

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

Pina-Hernandez, Carlos; Koshelev, Alexander; Dhuey, Scott

A novel method to realizing printed active photonic devices was developed using nanoimprint lithography (NIL), combining a printable high-refractive index material and colloidal CdSe/CdS quantum dots (QDs) for applications in the visible region. Active media QDs were applied in two different ways: embedded inside a printable high-refractive index matrix to form an active printable hybrid nanocomposite, and used as a uniform coating on top of printed photonic devices. As a proof-of-demonstration for printed active photonic devices, two-dimensional (2-D) photonic crystals as well as 1D and 2D photonic nanocavities were successfully fabricated following a simple reverse-nanoimprint process. We observed enhanced photoluminescencemore » from the 2D photonic crystal and the 1D nanocavities. Outstandingly, the process presented in this study is fully compatible with large-scale manufacturing where the patterning areas are only limited by the size of the corresponding mold. This work shows that the integration of active media and functional materials is a promising approach to the realization of integrated photonics for visible light using high throughput technologies. We believe that this work represents a powerful and cost-effective route for the development of numerous nanophotonic structures and devices that will lead to the emergence of new applications.« less

Secondary radiation measurements for particle therapy applications: prompt photons produced by 4He, 12C and 16O ion beams in a PMMA target.

PubMed

Mattei, I; Bini, F; Collamati, F; De Lucia, E; Frallicciardi, P M; Iarocci, E; Mancini-Terracciano, C; Marafini, M; Muraro, S; Paramatti, R; Patera, V; Piersanti, L; Pinci, D; Rucinski, A; Russomando, A; Sarti, A; Sciubba, A; Solfaroli Camillocci, E; Toppi, M; Traini, G; Voena, C; Battistoni, G

2017-02-21

Charged particle beams are used in particle therapy (PT) to treat oncological patients due to their selective dose deposition in tissues with respect to the photons and electrons used in conventional radiotherapy. Heavy (Z  >  1) PT beams can additionally be exploited for their high biological effectiveness in killing cancer cells. Nowadays, protons and carbon ions are used in PT clinical routines. Recently, interest in the potential application of helium and oxygen beams has been growing. With respect to protons, such beams are characterized by their reduced multiple scattering inside the body, increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands online dose monitoring techniques, crucial to improving the quality assurance of any treatment: possible patient mis-positioning and biological tissue changes with respect to the planning CT scan could negatively affect the outcome of the therapy. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Among these secondary products, prompt photons are produced by nuclear de-excitation processes, and at present, different dose monitoring and beam range verification techniques based on prompt-γ detection are being proposed. It is hence of importance to perform γ yield measurement in therapeutic-like conditions. In this paper we report on the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a poly-methyl methacrylate (PMMA) beam stopping target. The measurements were performed at the Heidelberg Ion-Beam Therapy Center (HIT) with beams of different energies. An LYSO scintillator, placed at [Formula: see text] and [Formula: see text] with respect to the beam direction, was used as the photon detector. The obtained γ yields for the carbon ion beams are compared with results from the literature, while no other results from helium and oxygen beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-γ-based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.

Secondary radiation measurements for particle therapy applications: prompt photons produced by 4He, 12C and 16O ion beams in a PMMA target

NASA Astrophysics Data System (ADS)

Mattei, I.; Bini, F.; Collamati, F.; De Lucia, E.; Frallicciardi, P. M.; Iarocci, E.; Mancini-Terracciano, C.; Marafini, M.; Muraro, S.; Paramatti, R.; Patera, V.; Piersanti, L.; Pinci, D.; Rucinski, A.; Russomando, A.; Sarti, A.; Sciubba, A.; Solfaroli Camillocci, E.; Toppi, M.; Traini, G.; Voena, C.; Battistoni, G.

2017-02-01

Charged particle beams are used in particle therapy (PT) to treat oncological patients due to their selective dose deposition in tissues with respect to the photons and electrons used in conventional radiotherapy. Heavy (Z  >  1) PT beams can additionally be exploited for their high biological effectiveness in killing cancer cells. Nowadays, protons and carbon ions are used in PT clinical routines. Recently, interest in the potential application of helium and oxygen beams has been growing. With respect to protons, such beams are characterized by their reduced multiple scattering inside the body, increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands online dose monitoring techniques, crucial to improving the quality assurance of any treatment: possible patient mis-positioning and biological tissue changes with respect to the planning CT scan could negatively affect the outcome of the therapy. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Among these secondary products, prompt photons are produced by nuclear de-excitation processes, and at present, different dose monitoring and beam range verification techniques based on prompt-γ detection are being proposed. It is hence of importance to perform γ yield measurement in therapeutic-like conditions. In this paper we report on the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a poly-methyl methacrylate (PMMA) beam stopping target. The measurements were performed at the Heidelberg Ion-Beam Therapy Center (HIT) with beams of different energies. An LYSO scintillator, placed at {{60}\\circ} and {{90}\\circ} with respect to the beam direction, was used as the photon detector. The obtained γ yields for the carbon ion beams are compared with results from the literature, while no other results from helium and oxygen beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-γ-based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.

SPECT study of low intensity He-Ne laser intravascular irradiation therapy for brain infarction

NASA Astrophysics Data System (ADS)

Xiao, Xue-Chang; Dong, Jia-Zheng; Chu, Xiao-Fan; Jia, Shao-Wei; Liu, Timon C.; Jiao, Jian-Ling; Zheng, Xi-Yuan; Zhou, Ci-Xiong

2003-12-01

We used single photon emission computed tomography (SPECT) in brain perfusion imaging to study the changes of regional cerebral blood flow (rCBF) and cerebral function in brain infarction patients treated with intravascular laser irradiation of blood (ILIB). 17 of 35 patients with brain infarction were admitted to be treated by ILIB on the base of standard drug therapy, and SPECT brain perfusion imaging was performed before and after ILIB therapy with self-comparison. The results were analyzed in quantity with brain blood flow function change rate (BFCR%) model. Effect of ILIB during the therapy process in the other 18 patients were also observed. In the 18 patients, SPECT indicated an improvement of rCBF (both in focus and in total brain) and cerebral function after a 30 min-ILIB therapy. And the 17 patients showed an enhancement of total brain rCBF and cerebral function after ILIB therapy in comparison with that before, especially for the focus side of the brain. The enhancement for focus itself was extremely obvious with a higher significant difference (P<0.0001). The mirror regions had no significant change (P>0.05). BFCR% of foci was prominently higher than that of mirror regions (P<0.0001). In conclusion, the ILIB therapy can improve rCBF and cerebral function and activate brain cells of patients with brain infarction. The results denote new evidence of ILIB therapy for those patients with cerebral ischemia.

Two-photon activation of endogenous store-operated calcium channels without optogenetics

NASA Astrophysics Data System (ADS)

Cheng, Pan; Tang, Wanyi; He, Hao

2018-02-01

Store-operated calcium (SOC) channels, regulated by intracellular Ca2+ store, are the essential pathway of calcium signaling and participate in a wide variety of cellular activities such as gene expression, secretion and immune response1. However, our understanding and regulation of SOC channels are mainly based on pharmacological methods. Considering the unique advantages of optical control, optogenetic control of SOC channels has been developed2. However, the process of genetic engineering to express exogenous light-sensitive protein is complicated, which arouses concerns about ethic difficulties in some research of animal and applications in human. In this report, we demonstrate rapid, robust and reproducible two-photon activation of endogenous SOC channels by femtosecond laser without optogenetics. We present that the short-duration two-photon scanning on subcellular microregion induces slow Ca2+ influx from extracellular medium, which can be eliminated by removing extracellular Ca2+. Block of SOC channels using various pharmacological inhibitors or knockdown of SOC channels by RNA interference reduce the probability of two-photon activated Ca2+ influx. On the contrary, overexpression of SOC channels can increase the probability of Ca2+ influx by two-photon scanning. These results collectively indicate Ca2+ influx through two-photon activated SOC channels. Different from classical pathway of SOC entry activated by Ca2+ store depletion, STIM1, the sensor protein of Ca2+ level in endoplasmic reticulum, does not show any aggregation or migration in this two-photon activated Ca2+ influx, which rules out the possibility of intracellular Ca2+ store depletion. Thereby, we propose this all-optical method of two-photon activation of SOC channels is of great potential to be widely applied in the research of cell calcium signaling and related biological research.

Chemical luminescence measurement of singlet oxygen generated by photodynamic therapy in solutions in real time

NASA Astrophysics Data System (ADS)

Luo, Shiming; Xing, Da; Zhou, Jing; Qin, Yanfang; Chen, Qun

2005-04-01

Photodynamic therapy (PDT) is a cancer therapy that utilizes optical energy to activate a photosensitizer drug in a target tissue. Reactive oxygen species (ROS), such as 1O2 and superoxide, are believed to be the major cytotoxic agents involved in PDT. Although current PDT dosimetry mostly involves measurements of light and photosensitizer doses delivered to a patient, the quantification of ROS production during a treatment would be the ultimate dosimetry of PDT. Technically, it is very difficult and expensive to directly measure the fluorescence from 1O2, due to its extreme short lifetime and weak signal strength. In this paper, Photofrin(R) and 635nm laser were used to generate 1O2 and superoxide in a PDT in solution. Compound 3,7- dihydro-6-{4-[2-(N"-(5-fluoresceinyl) thioureido) ethoxy] phenyl}-2- methylimidazo{1,2-a} pyrazin-3-one sodium salt,an Cyp- ridina luciferin analog commonly referred as FCLA, was used as a chemical reporter of ROS. The 532nm chemiluminescence (CL) from the reaction of the FCLA and ROS was detected with a photon multiplier tube (PMT) system operating at single photon counting mode. With the setup, we have made detections of ROS generated by PDT in real time. By varying the amount of conventional PDT dosage (photosensitizer concentration, light irradiation fluence and its delivery rate) and the amount of FCLA, the intensity of CL and its consumption rate were investigated. The results show that the intensity and temporal profile of CL are highly related to the PDT treatment parameters. This suggests that FCLA CL may provide a highly potential alternative for ROS detection during PDT.

Long-term Cosmetic Outcomes and Toxicities of Proton Beam Therapy Compared With Photon-Based 3-Dimensional Conformal Accelerated Partial-Breast Irradiation: A Phase 1 Trial

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

Galland-Girodet, Sigolène; Pashtan, Itai; MacDonald, Shannon M.

2014-11-01

Purpose: To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. Methods and Materials: From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. Results: At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBTmore » patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). Conclusions: Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity.« less

Guidelines on the implementation of diode in vivo dosimetry programs for photon and electron external beam therapy.

PubMed

Alecu, R; Loomis, T; Alecu, J; Ochran, T

1999-01-01

Semiconductor diodes offer many advantages for clinical dosimetry: high sensitivity, real-time readout, simple instrumentation, robustness and air pressure independence. The feasibility and usefulness of in vivo dosimetry with diodes has been shown by numerous publications, but very few, if any, refer to the utilization of diodes in electron beam dosimetry. The purpose of this paper is to present our methods for implementing an effective IVD program for external beam therapy with photons and electrons and to evaluate a new type of diodes. Methods of deciding on reasonable action levels along with calibration procedures, established according to the type of measurements intended to be performed and the action limits, are discussed. Correction factors to account for nonreference clinical conditions for new types of diodes (designed for photon and electron beams) are presented and compared with those required by older models commercially available. The possibilities and limitations of each type of diode are presented, emphasizing the importance of using the appropriate diode for each task and energy range.

Charged-particle therapy in cancer: clinical uses and future perspectives.

PubMed

Durante, Marco; Orecchia, Roberto; Loeffler, Jay S

2017-08-01

Radiotherapy with high-energy charged particles has become an attractive therapeutic option for patients with several tumour types because this approach better spares healthy tissue from radiation than conventional photon therapy. The cost associated with the delivery of charged particles, however, is higher than that of even the most elaborate photon-delivery technologies. Reliable evidence of the relative cost-effectiveness of both modalities can only come from the results of randomized clinical trials. Thus, the hurdles that currently limit direct comparisons of these two approaches in clinical trials, especially those related to insurance coverage, should be removed. Herein, we review several randomized trials of charged-particle therapies that are ongoing, with results that will enable selective delivery to patients who are most likely to benefit from them. We also discuss aspects related to radiobiology, including the immune response and hypoxia, which will need to be taken into consideration in future randomized trials to fully exploit the potential of charged particles.

Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring

PubMed Central

Avci, Pinar; Gupta, Asheesh; Sadasivam, Magesh; Vecchio, Daniela; Pam, Zeev; Pam, Nadav; Hamblin, Michael R

2013-01-01

Low-level laser (light) therapy (LLLT) is a fast-growing technology used to treat a multitude of conditions that require stimulation of healing, relief of pain and inflammation, and restoration of function. Although the skin is the organ that is naturally exposed to light more than any other organ, it still responds well to red and near-infrared wavelengths. The photons are absorbed by mitochondrial chromophores in skin cells. Consequently electron transport, adenosine triphosphate (ATP) nitric oxide release, blood flow, reactive oxygen species increase and diverse signaling pathways get activated. Stem cells can be activated allowing increased tissue repair and healing. In dermatology, LLLT has beneficial effects on wrinkles, acne scars, hypertrophic scars, and healing of burns. LLLT can reduce UV damage both as a treatment and as a prophylaxis. In pigmentary disorders such as vitiligo, LLLT can increase pigmentation by stimulating melanocyte proliferation and reduce depigmentation by inhibiting autoimmunity. Inflammatory diseases such as psoriasis and acne can also benefit. The non-invasive nature and almost complete absence of side-effects encourages further testing in dermatology. PMID:24049929

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced esophageal squamous cell carcinoma.

PubMed

Hirano, Yasuhiro; Onozawa, Masakatsu; Hojo, Hidehiro; Motegi, Atsushi; Zenda, Sadatomo; Hotta, Kenji; Moriya, Shunsuke; Tachibana, Hidenobu; Nakamura, Naoki; Kojima, Takashi; Akimoto, Tetsuo

2018-02-09

The purpose of this study was to perform a dosimetric comparison between proton beam therapy (PBT) and photon radiation therapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were treated with PBT in our institution. In addition, we evaluated the correlation between toxicities and dosimetric parameters, especially the doses to normal lung or heart tissue, to clarify the clinical advantage of PBT over photon radiation therapy. A total of 37 consecutive patients with Stage III thoracic ESCC who had received PBT with or without concurrent chemotherapy between October 2012 and December 2015 were evaluated in this study. The dose distributions of PBT were compared with those of dummy 3-dimensional conformal radiation therapy (3DCRT) and Intensity Modulated Radiation Therapy (IMRT), focusing especially on the doses to organs at risk, such as normal lung and heart tissue. Of the 37 patients, the data from 27 patients were analyzed. Among these 27 patients, four patients (15%) developed grade 2 pericardial effusion as a late toxicity. None of the patients developed grade 3 or worse acute or late pulmonary and cardiac toxicities. When the dosimetric parameters between PBT and planned 3DCRT were compared, all the PBT domestic variables for the lung dose except for lung V10 GyE and V15 GyE were significantly lower than those for the dummy 3DCRT plans, and the PBT domestic variables for the heart dose were also significantly lower than those for the dummy 3DCRT plans. When the PBT and IMRT plans were compared, all the PBT domestic variables for the doses to the lung and heart were significantly lower than those for the dummy IMRT plans. Regarding the correlation between the grades of toxicities and the dosimetric parameters, no significant correlation was seen between the occurrence of grade 2 pericardial effusion and the dose to the heart. When the dosimetric parameters of the dose distributions for the treatment of patients with locally advanced stage III ESCC were compared between PBT and 3DCRT or IMRT, PBT enabled a significant reduction in the dose to the lung and heart, compared with 3DCRT or IMRT.

A high-brightness, electron-based source of polarized photons and neutrons

NASA Astrophysics Data System (ADS)

Spencer, J. E.

1999-06-01

A compact and comparatively inexpensive system that is practical for universities is described based on a low-energy, electron storage ring with at least one undulator based oscillator to store photons. If the oscillator cavity length is relativistically corrected to be an harmonic of the ring circumference (LC=βLRn/nB with nB the number of bunches), higher-energy, secondary photons from Compton backscattering may become significant. Then, besides synchrotron radiation from the ring dipoles and damping wigglers as well as undulator photons, there are frequency upshifted Compton photons and photoneutrons from low Q-value targets such as Beryllium (Qn=-1.66) or Deuterium (Qn=-2.22 MeV). For 100 MeV electron bunches, an adjustable-phase, planar, helical undulator can be made to produce circularly polarized UV photons having a fundamental ɛγ1=11.1 eV. If these photons are stored in a multimode, hole-coupled resonator they produce a Compton endpoint energy up to ɛγ2=1.7 MeV. When incident on a Be conversion target these secondary photons make unmoderated, epithermal neutrons having mean energy ɛn=24.8±6.8 keV from the two-body reaction Be9+γ→n+Be8(→2α)with negligible, residual radioactivity. The system is shown in Fig. 1. When the target is unpolarized, one expects neutron rates of 1011 epithermal n/s for 1015 Comptons/s and a circulating current of 1 A with polarizations PRHC(n⃗)=-0.5, PLHC(n⃗)=0.5, both with reduced flux, and PLin(n⃗)=0. With a 1 cm thick cylindrical tungsten sheath surrounding the Be to attenuate scattered photons exiting at 90° to the incident photons, there is a peak neutron flux of ≈109 epithermal n/s/cm2 cylindrically symmetric around the surface. No attempt was made to optimize this because there is still no accepted treatment protocol (dose rates or preferred neutron energy distribution). Although these factors depend on the individual case, several thousand BNCT treatments per year appear feasible. A potential clinical advantage of this system is that it also provides the photon beams required for analogs of NCT such as photon activation therapy PAT. Other medical applications, depending on electron energy, include real-time production of radioactive nuclides (both proton and neutron rich) e.g. tracers for PET scans useful for measuring boron uptake rate and distribution prior to treatment. While the primary electron energy depends on the application, higher energies are more versatile and technically simpler. Certain innovations that make such a system feasible are discussed.

Accuracy of Rhenium-188 SPECT/CT activity quantification for applications in radionuclide therapy using clinical reconstruction methods.

PubMed

Esquinas, Pedro L; Uribe, Carlos F; Gonzalez, M; Rodríguez-Rodríguez, Cristina; Häfeli, Urs O; Celler, Anna

2017-07-20

The main applications of 188 Re in radionuclide therapies include trans-arterial liver radioembolization and palliation of painful bone-metastases. In order to optimize 188 Re therapies, the accurate determination of radiation dose delivered to tumors and organs at risk is required. Single photon emission computed tomography (SPECT) can be used to perform such dosimetry calculations. However, the accuracy of dosimetry estimates strongly depends on the accuracy of activity quantification in 188 Re images. In this study, we performed a series of phantom experiments aiming to investigate the accuracy of activity quantification for 188 Re SPECT using high-energy and medium-energy collimators. Objects of different shapes and sizes were scanned in Air, non-radioactive water (Cold-water) and water with activity (Hot-water). The ordered subset expectation maximization algorithm with clinically available corrections (CT-based attenuation, triple-energy window (TEW) scatter and resolution recovery was used). For high activities, the dead-time corrections were applied. The accuracy of activity quantification was evaluated using the ratio of the reconstructed activity in each object to this object's true activity. Each object's activity was determined with three segmentation methods: a 1% fixed threshold (for cold background), a 40% fixed threshold and a CT-based segmentation. Additionally, the activity recovered in the entire phantom, as well as the average activity concentration of the phantom background were compared to their true values. Finally, Monte-Carlo simulations of a commercial [Formula: see text]-camera were performed to investigate the accuracy of the TEW method. Good quantification accuracy (errors  <10%) was achieved for the entire phantom, the hot-background activity concentration and for objects in cold background segmented with a 1% threshold. However, the accuracy of activity quantification for objects segmented with 40% threshold or CT-based methods decreased (errors  >15%), mostly due to partial-volume effects. The Monte-Carlo simulations confirmed that TEW-scatter correction applied to 188 Re, although practical, yields only approximate estimates of the true scatter.

Recent Advances in Cancer Therapy Based on Dual Mode Gold Nanoparticles

PubMed Central

Spyratou, Ellas; Makropoulou, Mersini; Sihver, Lembit

2017-01-01

Many tumor-targeted strategies have been used worldwide to limit the side effects and improve the effectiveness of therapies, such as chemotherapy, radiotherapy (RT), etc. Biophotonic therapy modalities comprise very promising alternative techniques for cancer treatment with minimal invasiveness and side-effects. These modalities use light e.g., laser irradiation in an extracorporeal or intravenous mode to activate photosensitizer agents with selectivity in the target tissue. Photothermal therapy (PTT) is a minimally invasive technique for cancer treatment which uses laser-activated photoabsorbers to convert photon energy into heat sufficient to induce cells destruction via apoptosis, necroptosis and/or necrosis. During the last decade, PTT has attracted an increased interest since the therapy can be combined with customized functionalized nanoparticles (NPs). Recent advances in nanotechnology have given rise to generation of various types of NPs, like gold NPs (AuNPs), designed to act both as radiosensitizers and photothermal sensitizing agents due to their unique optical and electrical properties i.e., functioning in dual mode. Functionalized AuNPS can be employed in combination with non-ionizing and ionizing radiation to significantly improve the efficacy of cancer treatment while at the same time sparing normal tissues. Here, we first provide an overview of the use of NPs for cancer therapy. Then we review many recent advances on the use of gold NPs in PTT, RT and PTT/RT based on different types of AuNPs, irradiation conditions and protocols. We refer to the interaction mechanisms of AuNPs with cancer cells via the effects of non-ionizing and ionizing radiations and we provide recent existing experimental data as a baseline for the design of optimized protocols in PTT, RT and PTT/RT combined treatment. PMID:29257070

Nonoperative treatment of symptomatic spondylolysis.

PubMed

Kurd, Mark F; Patel, Deepan; Norton, Robert; Picetti, George; Friel, Brian; Vaccaro, Alexander R

2007-12-01

Symptomatic spondylolysis resulting from a stress fracture of the pars interarticularis is a cause of low back pain in the juvenile and adolescent patient. Treatment is conservative in the majority of cases. To analyze the outcome of patients with symptomatic isthmic spondylolysis treated nonoperatively with a custom fit thoracolumbar orthosis and activity cessation for 3 months followed by an organized physical therapy program. Retrospective case series. Four hundred thirty-six juvenile and adolescent patients with spondylolysis. Pain improvement, hamstring flexibility, range of motion, resolution of back spasms, and return to previous activities. Retrospective review of 436 juvenile and adolescent patients with symptomatic spondylolysis confirmed by single-photon emission computed tomography or computed tomography. Clinical outcomes were assessed through patient history and physical examination. Ninety-five percent of patients achieved excellent results according to a modified Odom's Criteria. The remaining 5% of patients achieved good results as they required occasional nonsteroidal anti-inflammatory drugs to relieve pain. Back spasms were resolved and hamstring tightness and range of motion returned to normal in all patients. All patients returned to their preinjury activity level. No patients went on to surgery. Symptomatic juvenile and adolescent patients with an isthmus spondylolysis may be effectively managed with a custom fit thoracolumbar orthosis brace and activity cessation for approximately 3 months followed by an organized physical therapy program.

N values estimation based on photon flux simulation with Geant4 toolkit.

PubMed

Sun, Z J; Danjaji, M; Kim, Y

2018-06-01

N values are routinely introduced in photon activation analysis (PAA) as the ratio of special activities of product nuclides to compare the relative intensities of different reaction channels. They determine the individual activities of each radioisotope and the total activity of the sample, which are the primary concerns of radiation safety. Traditionally, N values are calculated from the gamma spectroscopy in real measurements by normalizing the activities of individual nuclides to the reference reaction [ 58 Ni(γ, n) 57 Ni] of the nickel monitor simultaneously irradiated in photon activation. Is it possible to use photon flux simulated by Monte Carlo software to calculate N values even before the actual irradiation starts? This study has applied Geant4 toolkit, a popular platform of simulating the passage of particles through matter, to generate photon flux in the samples. Assisted with photonuclear cross section from IAEA database, it is feasible to predict N values in different experimental setups for simulated target material. We have validated of this method and its consistency with Geant4. Results also show that N values are highly correlated with the beam parameters of incoming electrons and the setup of the electron-photon converter. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Monte Carlo study on {sup 223}Ra imaging for unsealed radionuclide therapy

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

Takahashi, Akihiko, E-mail: takahsr@hs.med.kyushu-u.ac.jp; Miwa, Kenta; Sasaki, Masayuki

Purpose: Radium-223 ({sup 223}Ra), an α-emitting radionuclide, is used in unsealed radionuclide therapy for metastatic bone tumors. The demand for qualitative {sup 223}Ra imaging is growing to optimize dosimetry. The authors simulated {sup 223}Ra imaging using an in-house Monte Carlo simulation code and investigated the feasibility and utility of {sup 223}Ra imaging. Methods: The Monte Carlo code comprises two modules, HEXAGON and NAI. The HEXAGON code simulates the photon and electron interactions in the tissues and collimator, and the NAI code simulates the response of the NaI detector system. A 3D numeric phantom created using computed tomography images of amore » chest phantom was installed in the HEXAGON code. {sup 223}Ra accumulated in a part of the spine, and three x-rays and 19 γ rays between 80 and 450 keV were selected as the emitted photons. To evaluate the quality of the {sup 223}Ra imaging, the authors also simulated technetium-99m ({sup 99m}Tc) imaging under the same conditions and compared the results. Results: The sensitivities of the three photopeaks were 147 counts per unit of source activity (cps MBq{sup −1}; photopeak: 84 keV, full width of energy window: 20%), 166 cps MBq{sup −1} (154 keV, 15%), and 158 cps MBq{sup −1} (270 keV, 10%) for a low-energy general-purpose (LEGP) collimator, and those for the medium-energy general-purpose (MEGP) collimator were 33, 13, and 8.0 cps MBq{sup −1}, respectively. In the case of {sup 99m}Tc, the sensitivity was 55 cps MBq{sup −1} (141 keV, 20%) for LEGP and 52 cps MBq{sup −1} for MEGP. The fractions of unscattered photons of the total photons reflecting the image quality were 0.09 (84 keV), 0.03 (154 keV), and 0.02 (270 keV) for the LEGP collimator and 0.41, 0.25, and 0.50 for the MEGP collimator, respectively. Conversely, this fraction was approximately 0.65 for the simulated {sup 99m}Tc imaging. The sensitivity with the LEGP collimator appeared very high. However, almost all of the counts were because of photons that penetrated or were scattered in the collimator; therefore, the proportions of unscattered photons were small. Conclusions: Their simulation study revealed that the most promising scheme for {sup 223}Ra imaging is an 84-keV window using an MEGP collimator. The sensitivity of the photopeaks above 100 keV is too low for {sup 223}Ra imaging. A comparison of the fractions of unscattered photons reveals that the sensitivity and image quality are approximately two-thirds of those for {sup 99m}Tc imaging.« less

Fast determination of the spatially distributed photon fluence for light dose evaluation of PDT

NASA Astrophysics Data System (ADS)

Zhao, Kuanxin; Chen, Weiting; Li, Tongxin; Yan, Panpan; Qin, Zhuanping; Zhao, Huijuan

2018-02-01

Photodynamic therapy (PDT) has shown superiorities of noninvasiveness and high-efficiency in the treatment of early-stage skin cancer. Rapid and accurate determination of spatially distributed photon fluence in turbid tissue is essential for the dosimetry evaluation of PDT. It is generally known that photon fluence can be accurately obtained by Monte Carlo (MC) methods, while too much time would be consumed especially for complex light source mode or online real-time dosimetry evaluation of PDT. In this work, a method to rapidly calculate spatially distributed photon fluence in turbid medium is proposed implementing a classical perturbation and iteration theory on mesh Monte Carlo (MMC). In the proposed method, photon fluence can be obtained by superposing a perturbed and iterative solution caused by the defects in turbid medium to an unperturbed solution for the background medium and therefore repetitive MMC simulations can be avoided. To validate the method, a non-melanoma skin cancer model is carried out. The simulation results show the solution of photon fluence can be obtained quickly and correctly by perturbation algorithm.

Proton Beam Therapy

NASA Astrophysics Data System (ADS)

Paganetti, Harald

2017-01-01

Cancer therapy is a multi-modality approach including surgery, systemic or targeted chemotherapy, radiation (external beam or radionuclide), and immunotherapy. Radiation is typically administered using external beam photon therapy. Proton therapy has been around for more than 60 years but was restricted to research laboratories until the 1990s. Since then clinical proton therapy has been growing rapidly with currently more than 50 facilities worldwide. The interest in proton therapy stems from the physical properties of protons allowing for advanced dose sculpting around the target and sparing of healthy tissue. This review first evaluates the basics of proton therapy physics and technology and then outlines some of the current physical, biological, and clinical challenges. Solving these will ultimately determine whether proton therapy will continue on its path to becoming mainstream.

Radiation Therapy

MedlinePlus

... Radiation (also called x-rays, gamma rays, or photons) either kills tumor cells directly or interferes with ... treatment per day, five days a week, for two to seven weeks. Potiential Side Effects Most people ...

Time-resolved singlet-oxygen luminescence detection with an efficient and practical semiconductor single-photon detector

PubMed Central

Boso, Gianluca; Ke, Damei; Korzh, Boris; Bouilloux, Jordan; Lange, Norbert; Zbinden, Hugo

2015-01-01

In clinical applications, such as PhotoDynamic Therapy, direct singlet-oxygen detection through its luminescence in the near-infrared range (1270 nm) has been a challenging task due to its low emission probability and the lack of suitable single-photon detectors. Here, we propose a practical setup based on a negative-feedback avalanche diode detector that is a viable alternative to the current state-of-the art for different clinical scenarios, especially where geometric collection efficiency is limited (e.g. fiber-based systems, confocal microscopy, scanning systems etc.). The proposed setup is characterized with Rose Bengal as a standard photosensitizer and it is used to measure the singlet-oxygen quantum yield of a new set of photosensitizers for site-selective photodynamic therapy. PMID:26819830

Fast neutron irradiation for locally advanced pancreatic cancer

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

Smith, F.P.; Schein, P.S.; MacDonald, J.S.

1981-11-01

Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore,more » caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials.« less

Phospholipase C mediated Suppression of Dark Noise Enables Single Photon Detection in Drosophila Photoreceptors

PubMed Central

Katz, Ben; Minke, Baruch

2012-01-01

Drosophila photoreceptor cells use the ubiquitous G-protein-mediated phospholipase C (PLC) cascade to achieve ultimate single photon sensitivity. This is manifested in the single photon responses (quantum bumps). In photoreceptor cells, dark activation of Gqα molecules occurs spontaneously and produces unitary dark events (dark bumps). A high rate of spontaneous Gqα activation and dark bump production potentially hampers single photon detection. We found that in wild type flies the in vivo rate of spontaneous Gqα activation is very high. Nevertheless, this high rate is not manifested in a substantially high rate of dark bumps. Therefore, it is unclear how phototransduction suppresses dark bump production, arising from spontaneous Gqα activation, while still maintaining high-fidelity representation of single photons. In this study we show that reduced PLC catalytic activity selectively suppressed production of dark bumps but not light-induced bumps. Manipulations of PLC activity using PLC mutant flies and Ca2+ modulations revealed that a critical level of PLC activity is required to induce bump production. The required minimal level of PLC activity, selectively suppressed random production of single Gqα-activated dark bumps despite a high rate of spontaneous Gqα activation. This minimal PLC activity level is reliably obtained by photon induced synchronized activation of several neighboring Gqα molecules activating several PLC molecules, but not by random activation of single Gqα molecules. We thus demonstrate how a G-protein-mediated transduction system, with PLC as its target, selectively suppresses its intrinsic noise while preserving reliable signaling. PMID:22357856

SU-F-T-134: Can We Use the Same Dose Constrains Learnt From Photon World to Plan Proton for Lung Cancer?

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

Xiao, Z; Zou, J; Yue, N

Purpose: To evaluate if the same DVH constrains used in photon plans can be safely used to plan proton therapy for lung cancer. Since protons and photons have different dose deposition patterns, the hypothesis is following DVH constrains derived from photon world is not safe for proton. Methods: We retrospectively evaluated plans for 11 lung cancer patients. Each patient was planned with photon and proton following the same dose constrains. Dose statistics on PTV, normal lung, heart and esophagus were extracted for comparison. gEUD for normal lung was calculated and compared between proton and photon plans. We calculated series ofmore » gEUDs for each plan by varying the parameter “a” in gEUD formula from 0.1 to 3, covering the whole confidence interval. Results: For all patients, proton plans yield similar PTV coverage and lower dose to heart and esophagus than photon plans. Normal lung V5 was 32.3 % on average in proton plans than 55.4 % in photon. Normal lung gEUD monotonically increased with increasing “a” for all proton and photon plans. For a given patient, the gEUD-proton(a) had a steeper slope than gEUD-photon(a). The two curves crossed for 8 out of 11 patients when “a” = [0.1, 3]. a-crossing ranged from 0.8 to 2.44 with an average of 1.15. For a« less

Observation of extraordinary optical activity in planar chiral photonic crystals.

PubMed

Konishi, Kuniaki; Bai, Benfeng; Meng, Xiangfeng; Karvinen, Petri; Turunen, Jari; Svirko, Yuri P; Kuwata-Gonokami, Makoto

2008-05-12

Control of light polarization is a key technology in modern photonics including application to optical manipulation of quantum information. The requisite is to obtain large rotation in isotropic media with small loss. We report on extraordinary optical activity in a planar dielectric on-waveguide photonic crystal structure, which has no in-plane birefringence and shows polarization rotation of more than 25 degrees for transmitted light. We demonstrate that in the planar chiral photonic crystal, the coupling of the normally incident light wave with low-loss waveguide and Fabry-Pérot resonance modes results in a dramatic enhancement of the optical activity.

Dose evaluation of Grid Therapy using a 6 MV flattening filter-free (FFF) photon beam: A Monte Carlo study.

PubMed

Martínez-Rovira, Immaculada; Puxeu-Vaqué, Josep; Prezado, Yolanda

2017-10-01

Spatially fractionated radiotherapy is a strategy to overcome the main limitation of radiotherapy, i.e., the restrained normal tissue tolerances. A well-known example is Grid Therapy, which is currently performed at some hospitals using megavoltage photon beams delivered by Linacs. Grid Therapy has been successfully used in the management of bulky abdominal tumors with low toxicity. The aim of this work was to evaluate whether an improvement in therapeutic index in Grid Therapy can be obtained by implementing it in a flattening filter-free (FFF) Linac. The rationale behind is that the removal of the flattening filter shifts the beam energy spectrum towards lower energies and increase the photon fluence. Lower energies result in a reduction of lateral scattering and thus, to higher peak-to-valley dose ratios (PVDR) in normal tissues. In addition, the gain in fluence might allow using smaller beams leading a more efficient exploitation of dose-volume effects, and consequently, a better normal tissue sparing. Monte Carlo simulations were used to evaluate realistic dose distributions considering a 6 MV FFF photon beam from a standard medical Linac and a cerrobend mechanical collimator in different configurations: grid sizes of 0.3 × 0.3 cm 2 , 0.5 × 0.5 cm 2 , and 1 × 1 cm 2 and a corresponding center-to-center (ctc) distance of 0.6, 1, and 2 cm, respectively (total field size of 10 × 10 cm 2 ). As figure of merit, peak doses in depth, PVDR, output factors (OF), and penumbra values were assessed. Dose at the entrance is slightly higher than in conventional Grid Therapy. However, it is compensated by the large PVDR obtained at the entrance, reaching a maximum of 35 for a grid size of 1 × 1 cm 2 . Indeed, this grid size leads to very high PVDR values at all depths (≥ 10), which are much higher than in standard Grid Therapy. This may be beneficial for normal tissues but detrimental for tumor control, where a lower PVDR might be requested. In that case, higher valley doses in the tumor could be achieved by using an interlaced approach and/or adapting the ctc distance. The smallest grid size (0.3 × 0.3 cm 2 ) leads to low PVDR at all depths, comparable to standard Grid Therapy. However, the use of very thin beams might increase the normal tissue tolerances with respect to the grid size commonly used (1 × 1 cm 2 ). The gain in fluence provided by FFF implies that the important OF reduction (0.6) will not increase treatment time. Finally, the intermediate configuration (0.5 × 0.5 cm 2 ) provides high PVDR in the first 5 cm, and comparable PVDR to previous Grid Therapy works at depth. Therefore, this configuration might allow increasing the normal tissue tolerances with respect to Grid Therapy thanks to the higher PVDR and thinner beams, while a similar tumor control could be expected. The implementation of Grid Therapy in an FFF photon beam from medical Linac might lead to an improvement of the therapeutic index. Among the cases evaluated, a grid size of 0.5 × 0.5 cm 2 (1-cm-ctc) is the most advantageous configuration from the physics point of view. Radiobiological experiments are needed to fully explore this new avenue and to confirm our results. © 2017 American Association of Physicists in Medicine.

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.

Design of a fast multileaf collimator for radiobiological optimized IMRT with scanned beams of photons, electrons, and light ions.

PubMed

Svensson, Roger; Larsson, Susanne; Gudowska, Irena; Holmberg, Rickard; Brahme, Anders

2007-03-01

Intensity modulated radiation therapy is rapidly becoming the treatment of choice for most tumors with respect to minimizing damage to the normal tissues and maximizing tumor control. Today, intensity modulated beams are most commonly delivered using segmental multileaf collimation, although an increasing number of radiation therapy departments are employing dynamic multileaf collimation. The irradiation time using dynamic multileaf collimation depends strongly on the nature of the desired dose distribution, and it is difficult to reduce this time to less than the sum of the irradiation times for all individual peak heights using dynamic leaf collimation [Svensson et al., Phys. Med. Biol. 39, 37-61 (1994)]. Therefore, the intensity modulation will considerably increase the total treatment time. A more cost-effective procedure for rapid intensity modulation is using narrow scanned photon, electron, and light ion beams in combination with fast multileaf collimator penumbra trimming. With this approach, the irradiation time is largely independent of the complexity of the desired intensity distribution and, in the case of photon beams, may even be shorter than with uniform beams. The intensity modulation is achieved primarily by scanning of a narrow elementary photon pencil beam generated by directing a narrow well focused high energy electron beam onto a thin bremsstrahlung target. In the present study, the design of a fast low-weight multileaf collimator that is capable of further sharpening the penumbra at the edge of the elementary scanned beam has been simulated, in order to minimize the dose or radiation response of healthy tissues. In the case of photon beams, such a multileaf collimator can be placed relatively close to the bremsstrahlung target to minimize its size. It can also be flat and thin, i.e., only 15-25 mm thick in the direction of the beam with edges made of tungsten or preferably osmium to optimize the sharpening of the penumbra. The low height of the collimator will minimize edge scatter from glancing incidence. The major portions of the collimator leafs can then be made of steel or even aluminum, so that the total weight of the multileaf collimator will be as low as 10 kg, which may even allow high-speed collimation in real time in synchrony with organ movements. To demonstrate the efficiency of this collimator design in combination with pencil beam scanning, optimal radiobiological treatments of an advanced cervix cancer were simulated. Different geometrical collimator designs were tested for bremsstrahlung, electron, and light ion beams. With a 10 mm half-width elementary scanned photon beam and a steel collimator with tungsten edges, it was possible to make as effective treatments as obtained with intensity modulated beams of full resolution, i.e., here 5 mm resolution in the fluence map. In combination with narrow pencil beam scanning, such a collimator may provide ideal delivery of photons, electrons, or light ions for radiation therapy synchronized to breathing and other organ motions. These high-energy photon and light ion beams may allow three-dimensional in vivo verification of delivery and thereby clinical implementation of the BioArt approach using Biologically Optimized three-dimensional in vivo predictive Assay based adaptive Radiation Therapy [Brahme, Acta Oncol. 42, 123-126 (2003)].

Comparison of the Light Charged Particles on Scatter Radiation Dose in Thyroid Hadron Therapy

PubMed Central

Azizi, M; Mowlavi, AA

2014-01-01

Background: Hadron therapy is a novel technique of cancer radiation therapy which employs charged particles beams, 1H and light ions in particular. Due to their physical and radiobiological properties, they allow one to obtain a more conformal treatment, sparing better the healthy tissues located in proximity of the tumor and allowing a higher control of the disease. Objective: As it is well known, these light particles can interact with nuclei in the tissue, and produce the different secondary particles such as neutron and photon. These particles can damage specially the critical organs behind of thyroid gland. Methods: In this research, we simulated neck geometry by MCNPX code and calculated the light particles dose at distance of 2.14 cm in thyroid gland, for different particles beam: 1H, 2H, 3He, and 4He. Thyroid treatment is important because the spine and vertebrae is situated right behind to the thyroid gland on the posterior side. Results: The results show that 2H has the most total flux for photon and neutron, 1.944E-3 and 1.7666E-2, respectively. Whereas 1H and 3He have best conditions, 8.88609E-4 and 1.35431E-3 for photon, 4.90506E-4 and 4.34057E-3 for neutron, respectively. The same calculation has obtained for energy depositions for these particles. Conclusion: In this research, we investigated that which of these light particles can deliver the maximum dose to the normal tissues and the minimum dose to the tumor. By comparing these results for the mentioned light particles, we find out 1H and 3He is the best therapy choices for thyroid glands whereas 2H is the worst. PMID:25505774

First in situ TOF-PET study using digital photon counters for proton range verification.

PubMed

Cambraia Lopes, P; Bauer, J; Salomon, A; Rinaldi, I; Tabacchini, V; Tessonnier, T; Crespo, P; Parodi, K; Schaart, D R

2016-08-21

Positron emission tomography (PET) is the imaging modality most extensively tested for treatment monitoring in particle therapy. Optimal use of PET in proton therapy requires in situ acquisition of the relatively strong (15)O signal due to its relatively short half-life (~2 min) and high oxygen content in biological tissues, enabling shorter scans that are less sensitive to biological washout. This paper presents the first performance tests of a scaled-down in situ time-of-flight (TOF) PET system based on digital photon counters (DPCs) coupled to Cerium-doped Lutetium Yttrium Silicate (LYSO:Ce) crystals, providing quantitative results representative of a dual-head tomograph that complies with spatial constraints typically encountered in clinical practice (2  ×  50°, of 360°, transaxial angular acceptance). The proton-induced activity inside polymethylmethacrylate (PMMA) and polyethylene (PE) phantoms was acquired within beam pauses (in-beam) and immediately after irradiation by an actively-delivered synchrotron pencil-beam, with clinically relevant 125.67 MeV/u, 4.6  ×  10(8) protons s(-1), and 10(10) total protons. 3D activity maps reconstructed with and without TOF information are compared to FLUKA simulations, demonstrating the benefit of TOF-PET to reduce limited-angle artefacts using a 382 ps full width at half maximum coincidence resolving time. The time-dependent contributions from different radionuclides to the total count-rate are investigated. We furthermore study the impact of the acquisition time window on the laterally integrated activity depth-profiles, with emphasis on 2 min acquisitions starting at different time points. The results depend on phantom composition and reflect the differences in relative contributions from the radionuclides originating from carbon and oxygen. We observe very good agreement between the shapes of the simulated and measured activity depth-profiles for post-beam protocols. However, our results also suggest that available experimental cross sections underestimate the production of (10)C for in-beam acquisitions, which in PE results in an overestimation of the predicted activity range by 1.4 mm. The uncertainty in the activity range measured in PMMA using the DPC-based TOF-PET prototype setup equals 0.2 mm-0.3 mm.

First in situ TOF-PET study using digital photon counters for proton range verification

NASA Astrophysics Data System (ADS)

Cambraia Lopes, P.; Bauer, J.; Salomon, A.; Rinaldi, I.; Tabacchini, V.; Tessonnier, T.; Crespo, P.; Parodi, K.; Schaart, D. R.

2016-08-01

Positron emission tomography (PET) is the imaging modality most extensively tested for treatment monitoring in particle therapy. Optimal use of PET in proton therapy requires in situ acquisition of the relatively strong 15O signal due to its relatively short half-life (~2 min) and high oxygen content in biological tissues, enabling shorter scans that are less sensitive to biological washout. This paper presents the first performance tests of a scaled-down in situ time-of-flight (TOF) PET system based on digital photon counters (DPCs) coupled to Cerium-doped Lutetium Yttrium Silicate (LYSO:Ce) crystals, providing quantitative results representative of a dual-head tomograph that complies with spatial constraints typically encountered in clinical practice (2  ×  50°, of 360°, transaxial angular acceptance). The proton-induced activity inside polymethylmethacrylate (PMMA) and polyethylene (PE) phantoms was acquired within beam pauses (in-beam) and immediately after irradiation by an actively-delivered synchrotron pencil-beam, with clinically relevant 125.67 MeV/u, 4.6  ×  108 protons s-1, and 1010 total protons. 3D activity maps reconstructed with and without TOF information are compared to FLUKA simulations, demonstrating the benefit of TOF-PET to reduce limited-angle artefacts using a 382 ps full width at half maximum coincidence resolving time. The time-dependent contributions from different radionuclides to the total count-rate are investigated. We furthermore study the impact of the acquisition time window on the laterally integrated activity depth-profiles, with emphasis on 2 min acquisitions starting at different time points. The results depend on phantom composition and reflect the differences in relative contributions from the radionuclides originating from carbon and oxygen. We observe very good agreement between the shapes of the simulated and measured activity depth-profiles for post-beam protocols. However, our results also suggest that available experimental cross sections underestimate the production of 10C for in-beam acquisitions, which in PE results in an overestimation of the predicted activity range by 1.4 mm. The uncertainty in the activity range measured in PMMA using the DPC-based TOF-PET prototype setup equals 0.2 mm-0.3 mm.

Benchmarking of a treatment planning system for spot scanning proton therapy: Comparison and analysis of robustness to setup errors of photon IMRT and proton SFUD treatment plans of base of skull meningioma

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

Harding, R., E-mail: ruth.harding2@wales.nhs.uk; Trnková, P.; Lomax, A. J.

Purpose: Base of skull meningioma can be treated with both intensity modulated radiation therapy (IMRT) and spot scanned proton therapy (PT). One of the main benefits of PT is better sparing of organs at risk, but due to the physical and dosimetric characteristics of protons, spot scanned PT can be more sensitive to the uncertainties encountered in the treatment process compared with photon treatment. Therefore, robustness analysis should be part of a comprehensive comparison between these two treatment methods in order to quantify and understand the sensitivity of the treatment techniques to uncertainties. The aim of this work was tomore » benchmark a spot scanning treatment planning system for planning of base of skull meningioma and to compare the created plans and analyze their robustness to setup errors against the IMRT technique. Methods: Plans were produced for three base of skull meningioma cases: IMRT planned with a commercial TPS [Monaco (Elekta AB, Sweden)]; single field uniform dose (SFUD) spot scanning PT produced with an in-house TPS (PSI-plan); and SFUD spot scanning PT plan created with a commercial TPS [XiO (Elekta AB, Sweden)]. A tool for evaluating robustness to random setup errors was created and, for each plan, both a dosimetric evaluation and a robustness analysis to setup errors were performed. Results: It was possible to create clinically acceptable treatment plans for spot scanning proton therapy of meningioma with a commercially available TPS. However, since each treatment planning system uses different methods, this comparison showed different dosimetric results as well as different sensitivities to setup uncertainties. The results confirmed the necessity of an analysis tool for assessing plan robustness to provide a fair comparison of photon and proton plans. Conclusions: Robustness analysis is a critical part of plan evaluation when comparing IMRT plans with spot scanned proton therapy plans.« less

Commissioning optically stimulated luminescence in vivo dosimeters for fast neutron therapy.

PubMed

Young, Lori A; Yang, Fei; Woodworth, Davis; McCormick, Zephyr; Sandison, George

2016-01-01

Clinical in vivo dosimeters intended for use with photon and electron therapies have not been utilized for fast neutron therapy because they are highly susceptible to neutron damage. The objective of this work was to determine if a commercial optically stimulated luminescence (OSL) in vivo dosimetry system could be adapted for use in fast neutron therapy. A 50.5 MeV fast neutron beam generated by a clinical neutron therapy cyclotron was used to irradiate carbon doped aluminum oxide (Al2O3:C) optically simulated luminescence dosimeters (OSLDs) in a solid water phantom under standard calibration conditions, 150 cm SAD, 1.7 cm depth, and 10.3 × 10.0 cm field size. OSLD fading and electron trap depletion studies were performed with the OSLDs irradiated with 20 and 50 cGy and monitored over a 24-h period to determine the optimal time for reading the dosimeters during calibration. Four OSLDs per group were calibrated over a clinical dose range of 0-150 cGy. OSLD measurement uncertainties were lowered to within ±2%-3% of the expected dose by minimizing the effect of transient fading that occurs with neutron irradiation and maintaining individual calibration factors for each dosimeter. Dose dependent luminescence fading extended beyond the manufacturer's recommended 10 min period for irradiation with photon or electron beams. To minimize OSL variances caused by inconsistent fading among dosimeters, the observed optimal time for reading the OSLDs postirradiation was between 30 and 90 min. No field size, wedge factor, or gantry angle dependencies were observed in the OSLDs irradiated by the studied fast neutron beam. Measurements demonstrated that uncertainties less than ±3% were attainable in OSLDs irradiated with fast neutrons under clinical conditions. Accuracy and precision comparable to clinical OSL measurements observed with photons can be achieved by maintaining individual OSLD calibration factors and minimizing transient fading effects.

Commissioning optically stimulated luminescence in vivo dosimeters for fast neutron therapy

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

Young, Lori A., E-mail: layoung@uw.edu; Sandison, George; Yang, Fei

Purpose: Clinical in vivo dosimeters intended for use with photon and electron therapies have not been utilized for fast neutron therapy because they are highly susceptible to neutron damage. The objective of this work was to determine if a commercial optically stimulated luminescence (OSL) in vivo dosimetry system could be adapted for use in fast neutron therapy. Methods: A 50.5 MeV fast neutron beam generated by a clinical neutron therapy cyclotron was used to irradiate carbon doped aluminum oxide (Al{sub 2}O{sub 3}:C) optically simulated luminescence dosimeters (OSLDs) in a solid water phantom under standard calibration conditions, 150 cm SAD, 1.7more » cm depth, and 10.3 × 10.0 cm field size. OSLD fading and electron trap depletion studies were performed with the OSLDs irradiated with 20 and 50 cGy and monitored over a 24-h period to determine the optimal time for reading the dosimeters during calibration. Four OSLDs per group were calibrated over a clinical dose range of 0–150 cGy. Results: OSLD measurement uncertainties were lowered to within ±2%–3% of the expected dose by minimizing the effect of transient fading that occurs with neutron irradiation and maintaining individual calibration factors for each dosimeter. Dose dependent luminescence fading extended beyond the manufacturer’s recommended 10 min period for irradiation with photon or electron beams. To minimize OSL variances caused by inconsistent fading among dosimeters, the observed optimal time for reading the OSLDs postirradiation was between 30 and 90 min. No field size, wedge factor, or gantry angle dependencies were observed in the OSLDs irradiated by the studied fast neutron beam. Conclusions: Measurements demonstrated that uncertainties less than ±3% were attainable in OSLDs irradiated with fast neutrons under clinical conditions. Accuracy and precision comparable to clinical OSL measurements observed with photons can be achieved by maintaining individual OSLD calibration factors and minimizing transient fading effects.« less

Clinical application of in vivo treatment delivery verification based on PET/CT imaging of positron activity induced at high energy photon therapy

NASA Astrophysics Data System (ADS)

Janek Strååt, Sara; Andreassen, Björn; Jonsson, Cathrine; Noz, Marilyn E.; Maguire, Gerald Q., Jr.; Näfstadius, Peder; Näslund, Ingemar; Schoenahl, Frederic; Brahme, Anders

2013-08-01

The purpose of this study was to investigate in vivo verification of radiation treatment with high energy photon beams using PET/CT to image the induced positron activity. The measurements of the positron activation induced in a preoperative rectal cancer patient and a prostate cancer patient following 50 MV photon treatments are presented. A total dose of 5 and 8 Gy, respectively, were delivered to the tumors. Imaging was performed with a 64-slice PET/CT scanner for 30 min, starting 7 min after the end of the treatment. The CT volume from the PET/CT and the treatment planning CT were coregistered by matching anatomical reference points in the patient. The treatment delivery was imaged in vivo based on the distribution of the induced positron emitters produced by photonuclear reactions in tissue mapped on to the associated dose distribution of the treatment plan. The results showed that spatial distribution of induced activity in both patients agreed well with the delivered beam portals of the treatment plans in the entrance subcutaneous fat regions but less so in blood and oxygen rich soft tissues. For the preoperative rectal cancer patient however, a 2 ± (0.5) cm misalignment was observed in the cranial-caudal direction of the patient between the induced activity distribution and treatment plan, indicating a beam patient setup error. No misalignment of this kind was seen in the prostate cancer patient. However, due to a fast patient setup error in the PET/CT scanner a slight mis-position of the patient in the PET/CT was observed in all three planes, resulting in a deformed activity distribution compared to the treatment plan. The present study indicates that the induced positron emitters by high energy photon beams can be measured quite accurately using PET imaging of subcutaneous fat to allow portal verification of the delivered treatment beams. Measurement of the induced activity in the patient 7 min after receiving 5 Gy involved count rates which were about 20 times lower than that of a patient undergoing standard 18F-FDG treatment. When using a combination of short lived nuclides such as 15O (half-life: 2 min) and 11C (half-life: 20 min) with low activity it is not optimal to use clinical reconstruction protocols. Thus, it might be desirable to further optimize reconstruction parameters as well as to address hardware improvements in realizing in vivo treatment verification with PET/CT in the future. A significant improvement with regard to 15O imaging could also be expected by having the PET/CT unit located close to the radiation treatment room.

An in-beam PET system for monitoring ion-beam therapy: test on phantoms using clinical 62 MeV protons

NASA Astrophysics Data System (ADS)

Camarlinghi, N.; Sportelli, G.; Battistoni, G.; Belcari, N.; Cecchetti, M.; Cirrone, G. A. P.; Cuttone, G.; Ferretti, S.; Kraan, A.; Retico, A.; Romano, F.; Sala, P.; Straub, K.; Tramontana, A.; Del Guerra, A.; Rosso, V.

2014-04-01

Ion therapy allows the delivery of highly conformal dose taking advantage of the sharp depth-dose distribution at the Bragg-peak. However, patient positioning errors and anatomical uncertainties can cause dose distortions. To exploit the full potential of ion therapy, an accurate monitoring system of the ion range is needed. Among the proposed methods to monitor the ion range, Positron Emission Tomography (PET) has proven to be the most mature technique, allowing to reconstruct the β+ activity generated in the patient by the nuclear interaction of the ions, that can be acquired during or after the treatment. Taking advantages of the spatial correlation between positron emitters created along the ions path and the dose distribution, it is possible to reconstruct the ion range. Due to the high single rates generated during the beam extraction, the acquisition of the β+ activity is typically performed after the irradiation (cyclotron) or in between the synchrotron spills. Indeed the single photon rate can be one or more orders of magnitude higher than normal for cyclotron. Therefore, acquiring the activity during the beam irradiation requires a detector with a very short dead time. In this work, the DoPET detector, capable of sustaining the high event rate generated during the cyclotron irradiation, is presented. The capability of the system to acquire data during and after the irradiation will be demonstrated by showing the reconstructed activity for different PMMA irradiations performed using clinical dose rates and the 62 MeV proton beam at the CATANA-LNS-INFN. The reconstructed activity widths will be compared with the results obtained by simulating the proton beam interaction with the FLUKA Monte Carlo. The presented data are in good agreement with the FLUKA Monte Carlo.

Spatially Offset Raman Spectroscopy for Surgical Margin Evaluation During Breast Conserving Therapy

DTIC Science & Technology

2011-02-01

was connected to a 785 nm diode laser (I0785MB0350M, Innovative Photonics Solutions, Monmouth Junction, NJ) which delivered 80 mW of power to the...I0785MB0350M, Innovative Photonics Solutions, Monmouth Junction, New Jersey). The collection fibers deliv- ered light to a near-infrared-optimized...and Tecnology - calibrated tungsten-halogen lamp was used to correct the sys- tem response.29 After wavenumber binning (in 3.5 cm−1 steps given the

National Cancer Database Analysis of Proton Versus Photon Radiation Therapy in Non-Small Cell Lung Cancer

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

Higgins, Kristin A., E-mail: kristin.higgins@emory.edu; Winship Cancer Institute, Emory University, Atlanta, Georgia; O'Connell, Kelli

Purpose: To analyze outcomes and predictors associated with proton radiation therapy for non-small cell lung cancer (NSCLC) in the National Cancer Database. Methods and Materials: The National Cancer Database was queried to capture patients with stage I-IV NSCLC treated with thoracic radiation from 2004 to 2012. A logistic regression model was used to determine the predictors for utilization of proton radiation therapy. The univariate and multivariable association with overall survival were assessed by Cox proportional hazards models along with log–rank tests. A propensity score matching method was implemented to balance baseline covariates and eliminate selection bias. Results: A total of 243,822more » patients (photon radiation therapy: 243,474; proton radiation therapy: 348) were included in the analysis. Patients in a ZIP code with a median income of <$46,000 per year were less likely to receive proton treatment, with the income cohort of $30,000 to $35,999 least likely to receive proton therapy (odds ratio 0.63 [95% confidence interval (CI) 0.44-0.90]; P=.011). On multivariate analysis of all patients, non-proton therapy was associated with significantly worse survival compared with proton therapy (hazard ratio 1.21 [95% CI 1.06-1.39]; P<.01). On propensity matched analysis, proton radiation therapy (n=309) was associated with better 5-year overall survival compared with non-proton radiation therapy (n=1549), 22% versus 16% (P=.025). For stage II and III patients, non-proton radiation therapy was associated with worse survival compared with proton radiation therapy (hazard ratio 1.35 [95% CI 1.10-1.64], P<.01). Conclusions: Thoracic radiation with protons is associated with better survival in this retrospective analysis; further validation in the randomized setting is needed to account for any imbalances in patient characteristics, including positron emission tomography–computed tomography staging.« less

Application des codes de Monte Carlo à la radiothérapie par rayonnement à faible TEL

NASA Astrophysics Data System (ADS)

Marcié, S.

1998-04-01

In radiation therapy, there is low LET rays: photons of 60Co, photons and electrons to 4 at 25 MV created in a linac, photons 137Cs, of 192Ir and of 125I. To know the most exactly possible the dose to the tissu by this rays, software and measurements are used. With the development of the power and the capacity of computers, the application of Monte Carlo codes expand to the radiation therapy which have permitted to better determine effects of rays and spectra, to explicit parameters used in dosimetric calculation, to verify algorithms , to study measuremtents systems and phantoms, to calculate the dose in inaccessible points and to consider the utilization of new radionuclides. En Radiothérapie, il existe une variété, de rayonnements ? faible TLE : photons du cobalt 60, photons et ,électron de 4 à? 25 MV générés dans des accélérateurs linéaires, photons du césium 137, de l'iridium 192 et de l'iode 125. Pour connatre le plus exactement possible la dose délivrée aux tissus par ces rayonnements, des logiciels sont utilisés ainsi que des instruments de mesures. Avec le développement de la puissance et de la capacité, des calculateurs, l'application des codes de Monte Carlo s'est ,étendue ? la Radiothérapie ce qui a permis de mieux cerner les effets des rayonnements, déterminer les spectres, préciser les valeurs des paramètres utilisés dans les calculs dosimétriques, vérifier les algorithmes, ,étudier les systèmes de mesures et les fantomes utilisés, calculer la dose en des points inaccessibles ?à la mesure et envisager l'utilisation de nouveaux radio,éléments.

Clinical decision tool for optimal delivery of liver stereotactic body radiation therapy: Photons versus protons.

PubMed

Gandhi, Saumil J; Liang, Xing; Ding, Xuanfeng; Zhu, Timothy C; Ben-Josef, Edgar; Plastaras, John P; Metz, James M; Both, Stefan; Apisarnthanarax, Smith

2015-01-01

Stereotactic body radiation therapy (SBRT) for treatment of liver tumors is often limited by liver dose constraints. Protons offer potential for more liver sparing, but clinical situations in which protons may be superior to photons are not well described. We developed and validated a treatment decision model to determine whether liver tumors of certain sizes and locations are more suited for photon versus proton SBRT. Six spherical mock tumors from 1 to 6 cm in diameter were contoured on computed tomography images of 1 patient at 4 locations: dome, caudal, left medial, and central. Photon and proton plans were generated to deliver 50 Gy in 5 fractions to each tumor and optimized to deliver equivalent target coverage and maximal liver sparing. Using these plans, we developed a hypothesis-generating model to predict the optimal modality for maximal liver sparing based on tumor size and location. We then validated this model in 10 patients with liver tumors. Protons spared significantly more liver than photons for dome or central tumors ≥3 cm (dome: 134 ± 21 cm(3), P = .03; central: 108 ± 4 cm(3), P = .01). Our model correctly predicted the optimal SBRT modality for all 10 patients. For patients with dome or central tumors ≥3 cm, protons significantly increased the volume of liver spared (176 ± 21 cm(3), P = .01) and decreased the mean liver dose (8.4 vs 12.2 Gy, P = .01) while offering no significant advantage for tumors <3 cm at any location or for caudal and left medial tumors of any size. When feasible, protons should be considered as the radiation modality of choice for dome and central tumors >3 cm to allow maximal liver sparing and potentially reduce radiation toxicity. Protons should also be considered for any tumor >5 cm if photon plans fail to achieve adequate coverage or exceed the mean liver threshold. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Estimation and correction of produced light from prompt gamma photons on luminescence imaging of water for proton therapy dosimetry

NASA Astrophysics Data System (ADS)

Yabe, Takuya; Komori, Masataka; Toshito, Toshiyuki; Yamaguchi, Mitsutaka; Kawachi, Naoki; Yamamoto, Seiichi

2018-02-01

Although the luminescence images of water during proton-beam irradiation using a cooled charge-coupled device camera showed almost the same ranges of proton beams as those measured by an ionization chamber, the depth profiles showed lower Bragg peak intensities than those measured by an ionization chamber. In addition, a broad optical baseline signal was observed in depths that exceed the depth of the Bragg peak. We hypothesize that this broad baseline signal originates from the interaction of proton-induced prompt gamma photons with water. These prompt gamma photons interact with water to form high-energy Compton electrons, which may cause luminescence or Cherenkov emission from depths exceeding the location of the Bragg peak. To clarify this idea, we measured the luminescence images of water during the irradiations of protons in water with minimized parallax errors, and also simulated the produced light by the interactions of prompt gamma photons with water. We corrected the measured depth profiles of the luminescence images by subtracting the simulated distributions of the produced light by the interactions of prompt gamma photons in water. Corrections were also conducted using the estimated depth profiles of the light of the prompt gamma photons, as obtained from the off-beam areas of the luminescence images of water. With these corrections, we successfully obtained depth profiles that have almost identical distributions as the simulated dose distributions for protons. The percentage relative height of the Bragg peak with corrections to that of the simulation data increased to 94% from 80% without correction. Also, the percentage relative offset heights of the deeper part of the Bragg peak with corrections decreased to 0.2%-0.4% from 4% without correction. These results indicate that the luminescence imaging of water has potential for the dose distribution measurements for proton therapy dosimetry.

Photon upconversion towards applications in energy conversion and bioimaging

NASA Astrophysics Data System (ADS)

Sun, Qi-C.; Ding, Yuchen C.; Sagar, Dodderi M.; Nagpal, Prashant

2017-12-01

The field of plasmonics can play an important role in developing novel devices for application in energy and healthcare. In this review article, we consider the progress made in design and fabrication of upconverting nanoparticles and metal nanostructures for precisely manipulating light photons, with a wavelength of several hundred nanometers, at nanometer length scales, and describe how to tailor their interactions with molecules and surfaces so that two or more lower energy photons can be used to generate a single higher energy photon in a process called photon upconversion. This review begins by introducing the current state-of-the-art in upconverting nanoparticle synthesis and achievements in color tuning and upconversion enhancement. Through understanding and tailoring physical processes, color tuning and strong upconversion enhancement have been demonstrated by coupling with surface plasmon polariton waves, especially for low intensity or diffuse infrared radiation. Since more than 30% of incident sunlight is not utilized in most photovoltaic cells, this photon upconversion is one of the promising approaches to break the so-called Shockley-Queisser thermodynamic limit for a single junction solar cell. Furthermore, since the low energy photons typically cover the biological window of optical transparency, this approach can also be particularly beneficial for novel biosensing and bioimaging techniques. Taken together, the recent research boosts the applications of photon upconversion using designed metal nanostructures and nanoparticles for green energy, bioimaging, and therapy.

Optical Imaging of Ionizing Radiation from Clinical Sources

PubMed Central

Shaffer, Travis M.; Drain, Charles Michael

2016-01-01

Nuclear medicine uses ionizing radiation for both in vivo diagnosis and therapy. Ionizing radiation comes from a variety of sources, including x-rays, beam therapy, brachytherapy, and various injected radionuclides. Although PET and SPECT remain clinical mainstays, optical readouts of ionizing radiation offer numerous benefits and complement these standard techniques. Furthermore, for ionizing radiation sources that cannot be imaged using these standard techniques, optical imaging offers a unique imaging alternative. This article reviews optical imaging of both radionuclide- and beam-based ionizing radiation from high-energy photons and charged particles through mechanisms including radioluminescence, Cerenkov luminescence, and scintillation. Therapeutically, these visible photons have been combined with photodynamic therapeutic agents preclinically for increasing therapeutic response at depths difficult to reach with external light sources. Last, new microscopy methods that allow single-cell optical imaging of radionuclides are reviewed. PMID:27688469

Analysis on the emission and potential application of Cherenkov radiation in boron neutron capture therapy: A Monte Carlo simulation study.

PubMed

Shu, Di-Yun; Geng, Chang-Ran; Tang, Xiao-Bin; Gong, Chun-Hui; Shao, Wen-Cheng; Ai, Yao

2018-07-01

This paper was aimed to explore the physics of Cherenkov radiation and its potential application in boron neutron capture therapy (BNCT). The Monte Carlo toolkit Geant4 was used to simulate the interaction between the epithermal neutron beam and the phantom containing boron-10. Results showed that Cherenkov photons can only be generated from secondary charged particles of gamma rays in BNCT, in which the 2.223 MeV prompt gamma rays are the main contributor. The number of Cherenkov photons per unit mass generated in the measurement region decreases linearly with the increase of boron concentration in both water and tissue phantom. The work presented the fundamental basis for applications of Cherenkov radiation in BNCT. Copyright © 2018 Elsevier Ltd. All rights reserved.

A new method for photon transport in Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Sato, T.; Ogawa, K.

1999-12-01

Monte Carlo methods are used to evaluate data methods such as scatter and attenuation compensation in single photon emission CT (SPECT), treatment planning in radiation therapy, and in many industrial applications. In Monte Carlo simulation, photon transport requires calculating the distance from the location of the emitted photon to the nearest boundary of each uniform attenuating medium along its path of travel, and comparing this distance with the length of its path generated at emission. Here, the authors propose a new method that omits the calculation of the location of the exit point of the photon from each voxel and of the distance between the exit point and the original position. The method only checks the medium of each voxel along the photon's path. If the medium differs from that in the voxel from which the photon was emitted, the authors calculate the location of the entry point in the voxel, and the length of the path is compared with the mean free path length generated by a random number. Simulations using the MCAT phantom show that the ratios of the calculation time were 1.0 for the voxel-based method, and 0.51 for the proposed method with a 256/spl times/256/spl times/256 matrix image, thereby confirming the effectiveness of the algorithm.

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

Islam, M; Ahmad, S; Jin, H

Purpose: The out-of-beam dose is important for understanding the peripheral dose in radiation therapy. In proton radiotherapy, the study of out-of-beam dose is scarce and the treatment planning system (TPS) based on pencil beam algorithm cannot accurately predict the out-of-beam dose. This study investigates the out-of-beam dose for the single-room Mevion S250 double scattering proton therapy system using experimentally measured and treatment planning software generated data. The results are compared with those reported for conventional photon beam therapy. However, this study does not incorporate the neutron contribution in the scattered dose. Methods: A total of seven proton treatment plans weremore » generated using Varian Eclipse TPS for three different sites (brain, lung, and pelvis) in an anthropomorphic phantom. Three field sizes of 5×5, 10×10, and 20×20 cm{sup 2} (lung only) with typical clinical range (13.3–22.8 g/cm{sup 2}) and modulation widths (5.3–14.0 g/cm{sup 2}) were used. A single beam was employed in each treatment plan to deliver a dose of 181.8 cGy (200.0 cGy (RBE)) to the selected target. The out-of-beam dose was measured at 2.0, 5.0, 10.0, and 15.0 cm from the beam edge in the phantom using a thimble chamber (PTW TN31010). Results: The out-of-beam dose generally increased with field size, range, and volume irradiated. For all the plans, the scattered dose sharply fell off with distance. At 2.0 cm, the out-of-beam dose ranged from 0.35% to 2.16% of the delivered dose; however, the dose was clinically negligible (<0.3%) at a distance of 5.0 cm and greater. In photon therapy, the slightly greater out-of-beam dose was reported (TG36; 4%, 2%, and 1% for 2.0, 5.0, and 10.0 cm, respectively, using 6 MV beam). Conclusion: The measured out-of-beam dose in proton therapy excluding neutron contribution was observed higher than the TPS calculated dose and comparable to that of photon beam therapy.« less

Conjugated polymer and drug co-encapsulated nanoparticles for Chemo- and Photo-thermal Combination Therapy with two-photon regulated fast drug release

NASA Astrophysics Data System (ADS)

Yuan, Youyong; Wang, Zuyong; Cai, Pingqiang; Liu, Jie; Liao, Lun-De; Hong, Minghui; Chen, Xiaodong; Thakor, Nitish; Liu, Bin

2015-02-01

The spatial-temporal synchronization of photothermal therapy and chemotherapy is highly desirable for an efficient cancer treatment with synergistic effect. Herein, we developed a chemotherapeutic drug doxorubicin (DOX) and photothermal conjugated polymer (CP) co-loaded nanoplatform using a near-infrared (NIR) laser responsive amphiphilic brush copolymer as the encapsulation matrix. The obtained nanoparticles (NPs) exhibit good monodispersity and excellent stability, which can efficiently convert laser energy into thermal energy for photothermal therapy. Moreover, the hydrophobic polymer matrix bearing a number of 2-diazo-1,2-naphthoquinones (DNQ) moieties could be transformed to a hydrophilic one upon NIR two-photon laser irradiation, which leads to fast drug release. Furthermore, the surface modification of the NPs with cyclic arginine-glycine-aspartic acid (cRGD) tripeptide significantly enhances the accumulation of the NPs within integrin αvβ3 overexpressed cancer cells. The half-maximal inhibitory concentration (IC50) of the combination therapy is 13.7 μg mL-1, while the IC50 for chemotherapy and photothermal therapy alone is 147.8 μg mL-1 and 36.2 μg mL-1, respectively. The combination index (C.I.) is 0.48 (<1), which indicates the synergistic effect for chemotherapy and PTT. These findings provide an excellent NIR laser regulated nanoplatform for combined cancer treatment with synergistic effect due to the synchronous chemo- and photo-thermal therapy.

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

Arentsen, L; Lopater, Z; Dusenbery, K

Purpose: Duputren’s contracture (DC) is a benign disease characterized by abnormal thickening of the fascial surfaces of the hands or feet causing curling of the surface, functional impairment, weakness, and pain. The purpose of the investigation is to describe the radiation treatment approaches, compare these techniques, and discuss the potential side effects and complications of these techniques. Methods: Early stage DC has been treated with 120 kVp X rays but also with high-energy electrons or photons. High-energy electrons have been the radiation of choice but severe contracture of the hand makes it difficult to produce a plan with acceptable dosemore » uniformity. High-energy photons can overcome this difficulty either by directing a beam onto the palmer or back of the surface of the hand, including bolus to maximize the surface dose. We calculated the dose to the bone for the 120 kVp treatment using published %DD data and mass energy absorption coefficients for bone and muscle. Results: The dose to underlying bone from megavoltage photons and electrons is essentially the same, but dose to the bone for using 120 kVp can be 4–5 times greater due to the photoelectric effect. For the 30 Gy dose deliver using this technique, the dose to the bone could be 84–105 Gy after taking the penetration of the beam into account. After radiotherapy, there is often decreased osteoblastic activity and vascular fibrosis that leads to osteitis, atrophy, and decreased metabolic bone activity. Incidence of fractures occurs routinely above 60 Gy with higher doses potentially leading to higher incidences of bone complications. Conclusion: Radiation therapy for DC using low-energy X rays can deliver a prohibitively high dose to the underlying bone potentially leading to severe bone complications.« less

Orthovoltage radiation therapy treatment planning using Monte Carlo simulation: treatment of neuroendocrine carcinoma of the maxillary sinus

NASA Astrophysics Data System (ADS)

Gao, Wanbao; Raeside, David E.

1997-12-01

Dose distributions that result from treating a patient with orthovoltage beams are best determined with a treatment planning system that uses the Monte Carlo method, and such systems are not readily available. In the present work, the Monte Carlo method was used to develop a computer code for determining absorbed dose distributions in orthovoltage radiation therapy. The code was used in planning treatment of a patient with a neuroendocrine carcinoma of the maxillary sinus. Two lateral high-energy photon beams supplemented by an anterior orthovoltage photon beam were utilized in the treatment plan. For the clinical case and radiation beams considered, a reasonably uniform dose distribution is achieved within the target volume, while the dose to the lens of each eye is 4 - 8% of the prescribed dose. Therefore, an orthovoltage photon beam, when properly filtered and optimally combined with megavoltage beams, can be effective in the treatment of cancers below the skin, providing that accurate treatment planning is carried out to establish with accuracy and precision the doses to critical structures.

Controlling spontaneous emission with the local density of states of honeycomb photonic crystals

NASA Astrophysics Data System (ADS)

Tsai, Ya-Chih; Lin, Chien-Fan; Chang, Jui-Wen

2009-05-01

We calculated the local density of state for various positions in a photonic crystal of honeycomb lattice to study how the spontaneous emission rate of a radiating dipole is altered in the presence of the photonic crystal. The local density of states is found to be position-sensitive and its value can be enhanced or depressed relative to the density of states, depending on the location of the dipole. Our study shows that the density of states tends to underestimate the effect of a photonic crystal on the prohibition of light propagation, while on the contrary tends to overestimate the effect on the enhancement of light emission. The calculations also indicate that it is possible to tailor the spontaneous emission of an active medium by careful selecting its location in the photonic crystal. The results are helpful in determining the insertion location of the active medium and in evaluating the efficiency of active photonic crystal devices such as light-emitting diodes or lasers.

Shifting wavelengths of ultraweak photon emissions from dying melanoma cells: their chemical enhancement and blocking are predicted by Cosic's theory of resonant recognition model for macromolecules.

PubMed

Dotta, Blake T; Murugan, Nirosha J; Karbowski, Lukasz M; Lafrenie, Robert M; Persinger, Michael A

2014-02-01

During the first 24 h after removal from incubation, melanoma cells in culture displayed reliable increases in emissions of photons of specific wavelengths during discrete portions of this interval. Applications of specific filters revealed marked and protracted increases in infrared (950 nm) photons about 7 h after removal followed 3 h later by marked and protracted increases in near ultraviolet (370 nm) photon emissions. Specific wavelengths within the visible (400 to 800 nm) peaked 12 to 24 h later. Specific activators or inhibitors for specific wavelengths based upon Cosic's resonant recognition model elicited either enhancement or diminishment of photons at the specific wavelength as predicted. Inhibitors or activators predicted for other wavelengths, even within 10 nm, were less or not effective. There is now evidence for quantitative coupling between the wavelength of photon emissions and intrinsic cellular chemistry. The results are consistent with initial activation of signaling molecules associated with infrared followed about 3 h later by growth and protein-structural factors associated with ultraviolet. The greater-than-expected photon counts compared with raw measures through the various filters, which also function as reflective material to other photons, suggest that photons of different wavelengths might be self-stimulatory and could play a significant role in cell-to-cell communication.

Accelerators for Cancer Therapy

DOE R&D Accomplishments Database

Lennox, Arlene J.

2000-05-30

The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

Optical dosimetry probes to validate Monte Carlo and empirical-method-based NIR dose planning in the brain.

PubMed

Verleker, Akshay Prabhu; Shaffer, Michael; Fang, Qianqian; Choi, Mi-Ran; Clare, Susan; Stantz, Keith M

2016-12-01

A three-dimensional photon dosimetry in tissues is critical in designing optical therapeutic protocols to trigger light-activated drug release. The objective of this study is to investigate the feasibility of a Monte Carlo-based optical therapy planning software by developing dosimetry tools to characterize and cross-validate the local photon fluence in brain tissue, as part of a long-term strategy to quantify the effects of photoactivated drug release in brain tumors. An existing GPU-based 3D Monte Carlo (MC) code was modified to simulate near-infrared photon transport with differing laser beam profiles within phantoms of skull bone (B), white matter (WM), and gray matter (GM). A novel titanium-based optical dosimetry probe with isotropic acceptance was used to validate the local photon fluence, and an empirical model of photon transport was developed to significantly decrease execution time for clinical application. Comparisons between the MC and the dosimetry probe measurements were on an average 11.27%, 13.25%, and 11.81% along the illumination beam axis, and 9.4%, 12.06%, 8.91% perpendicular to the beam axis for WM, GM, and B phantoms, respectively. For a heterogeneous head phantom, the measured % errors were 17.71% and 18.04% along and perpendicular to beam axis. The empirical algorithm was validated by probe measurements and matched the MC results (R²0.99), with average % error of 10.1%, 45.2%, and 22.1% relative to probe measurements, and 22.6%, 35.8%, and 21.9% relative to the MC, for WM, GM, and B phantoms, respectively. The simulation time for the empirical model was 6 s versus 8 h for the GPU-based Monte Carlo for a head phantom simulation. These tools provide the capability to develop and optimize treatment plans for optimal release of pharmaceuticals in the treatment of cancer. Future work will test and validate these novel delivery and release mechanisms in vivo.

Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus.

PubMed

McGrath, H

2017-10-01

Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is "autoimmunity." Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these mechanisms reduces levels of anticardiolipin antibodies and protects during lupus pregnancy. Capping all of this is that UV-A1 irradiation is an essentially innocuous, highly manageable, and comfortable therapeutic agency.

Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus

PubMed Central

2017-01-01

Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is “autoimmunity.” Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these mechanisms reduces levels of anticardiolipin antibodies and protects during lupus pregnancy. Capping all of this is that UV-A1 irradiation is an essentially innocuous, highly manageable, and comfortable therapeutic agency. PMID:28480786

Photonic crystals for improving light absorption in organic solar cells

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

Duché, D., E-mail: david.duche@im2np.fr; Le Rouzo, J.; Masclaux, C.

2015-02-07

We theoretically and experimentally study the structuration of organic solar cells in the shape of photonic crystal slabs. By taking advantage of the optical properties of photonic crystals slabs, we show the possibility to couple Bloch modes with very low group velocities in the active layer of the cells. These Bloch modes, also called slow Bloch modes (SBMs), allow increasing the lifetime of photons within the active layer. Finally, we present experimental demonstration performed by using nanoimprint to directly pattern the standard poly-3-hexylthiophène:[6,6]-phenyl-C61-butiryc acid methyl ester organic semiconductor blend in thin film form in the shape of a photonic crystalmore » able to couple SBMs. In agreement with the model, optical characterizations will demonstrate significant photonic absorption gains.« less

A Variable Energy CW Compact Accelerator for Ion Cancer Therapy

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

Johnstone, Carol J.; Taylor, J.; Edgecock, R.

2016-03-10

Cancer is the second-largest cause of death in the U.S. and approximately two-thirds of all cancer patients will receive radiation therapy with the majority of the radiation treatments performed using x-rays produced by electron linacs. Charged particle beam radiation therapy, both protons and light ions, however, offers advantageous physical-dose distributions over conventional photon radiotherapy, and, for particles heavier than protons, a significant biological advantage. Despite recognition of potential advantages, there is almost no research activity in this field in the U.S. due to the lack of clinical accelerator facilities offering light ion therapy in the States. In January, 2013, amore » joint DOE/NCI workshop was convened to address the challenges of light ion therapy [1], inviting more than 60 experts from diverse fields related to radiation therapy. This paper reports on the conclusions of the workshop, then translates the clinical requirements into accelerat or and beam-delivery technical specifications. A comparison of available or feasible accelerator technologies is compared, including a new concept for a compact, CW, and variable energy light ion accelerator currently under development. This new light ion accelerator is based on advances in nonscaling Fixed-Field Alternating gradient (FFAG) accelerator design. The new design concepts combine isochronous orbits with long (up to 4m) straight sections in a compact racetrack format allowing inner circulating orbits to be energy selected for low-loss, CW extraction, effectively eliminating the high-loss energy degrader in conventional CW cyclotron designs.« less

Two-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks.

PubMed

Ebina, Teppei; Masamizu, Yoshito; Tanaka, Yasuhiro R; Watakabe, Akiya; Hirakawa, Reiko; Hirayama, Yuka; Hira, Riichiro; Terada, Shin-Ichiro; Koketsu, Daisuke; Hikosaka, Kazuo; Mizukami, Hiroaki; Nambu, Atsushi; Sasaki, Erika; Yamamori, Tetsuo; Matsuzaki, Masanori

2018-05-14

Two-photon imaging in behaving animals has revealed neuronal activities related to behavioral and cognitive function at single-cell resolution. However, marmosets have posed a challenge due to limited success in training on motor tasks. Here we report the development of protocols to train head-fixed common marmosets to perform upper-limb movement tasks and simultaneously perform two-photon imaging. After 2-5 months of training sessions, head-fixed marmosets can control a manipulandum to move a cursor to a target on a screen. We conduct two-photon calcium imaging of layer 2/3 neurons in the motor cortex during this motor task performance, and detect task-relevant activity from multiple neurons at cellular and subcellular resolutions. In a two-target reaching task, some neurons show direction-selective activity over the training days. In a short-term force-field adaptation task, some neurons change their activity when the force field is on. Two-photon calcium imaging in behaving marmosets may become a fundamental technique for determining the spatial organization of the cortical dynamics underlying action and cognition.

The PHOTON explorations: sixteen activities, many uses

NASA Astrophysics Data System (ADS)

Donnelly, Judith; Amatrudo, Kathryn; Robinson, Kathleen; Hanes, Fenna

2014-07-01

The PHOTON Explorations were adapted from favorite demonstrations of teacher participants in the PHOTON projects of the New England Board of Higher Education as well as Hands-on-Optics activities and interesting demonstrations found on the web. Since the end of project PHOTON2 in 2006, the sixteen inquiry-based activities have formed the basis for a hands-on "home lab" distance- learning course that has been used for college students, teacher professional development and corporate training. With the support of OSA, they have been brought to life in a series of sixteen short videos aimed at a middle school audience. The Explorations are regularly used as activities in outreach activities for middle and high school students and are introduced yearly to an international audience at an outreach workshop at SPIE's Optics and Photonics meeting. In this paper we will demonstrate the Explorations, trace their origins and explain the content. We will also provide details on the development of the Exploration videos, the online course, and outreach materials and give statistics on their use in each format. Links to online resources will be provided.

A method for energy window optimization for quantitative tasks that includes the effects of model-mismatch on bias: application to Y-90 bremsstrahlung SPECT imaging.

PubMed

Rong, Xing; Du, Yong; Frey, Eric C

2012-06-21

Quantitative Yttrium-90 ((90)Y) bremsstrahlung single photon emission computed tomography (SPECT) imaging has shown great potential to provide reliable estimates of (90)Y activity distribution for targeted radionuclide therapy dosimetry applications. One factor that potentially affects the reliability of the activity estimates is the choice of the acquisition energy window. In contrast to imaging conventional gamma photon emitters where the acquisition energy windows are usually placed around photopeaks, there has been great variation in the choice of the acquisition energy window for (90)Y imaging due to the continuous and broad energy distribution of the bremsstrahlung photons. In quantitative imaging of conventional gamma photon emitters, previous methods for optimizing the acquisition energy window assumed unbiased estimators and used the variance in the estimates as a figure of merit (FOM). However, for situations, such as (90)Y imaging, where there are errors in the modeling of the image formation process used in the reconstruction there will be bias in the activity estimates. In (90)Y bremsstrahlung imaging this will be especially important due to the high levels of scatter, multiple scatter, and collimator septal penetration and scatter. Thus variance will not be a complete measure of reliability of the estimates and thus is not a complete FOM. To address this, we first aimed to develop a new method to optimize the energy window that accounts for both the bias due to model-mismatch and the variance of the activity estimates. We applied this method to optimize the acquisition energy window for quantitative (90)Y bremsstrahlung SPECT imaging in microsphere brachytherapy. Since absorbed dose is defined as the absorbed energy from the radiation per unit mass of tissues in this new method we proposed a mass-weighted root mean squared error of the volume of interest (VOI) activity estimates as the FOM. To calculate this FOM, two analytical expressions were derived for calculating the bias due to model-mismatch and the variance of the VOI activity estimates, respectively. To obtain the optimal acquisition energy window for general situations of interest in clinical (90)Y microsphere imaging, we generated phantoms with multiple tumors of various sizes and various tumor-to-normal activity concentration ratios using a digital phantom that realistically simulates human anatomy, simulated (90)Y microsphere imaging with a clinical SPECT system and typical imaging parameters using a previously validated Monte Carlo simulation code, and used a previously proposed method for modeling the image degrading effects in quantitative SPECT reconstruction. The obtained optimal acquisition energy window was 100-160 keV. The values of the proposed FOM were much larger than the FOM taking into account only the variance of the activity estimates, thus demonstrating in our experiment that the bias of the activity estimates due to model-mismatch was a more important factor than the variance in terms of limiting the reliability of activity estimates.

The changing role of accelerators in radiation therapy

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

Hanson, W.F.

Conventional low energy x-rays have been used in radiation therapy since the turn of the century. Van de Graaff and Betatron accelerators changed the complexion of radiation therapy in the mid 1940's by providing significantly deeper penetrating photon beams and also providing therapeutic quality electron beams. The development of Cobalt-60 teletherapy in the mid 1950's suppressed the role of accelerators in radiation therapy for nearly 20 years. However, with the development of reliable isocentric rotating linear accelerators, accelerators are rapidly becoming the most popular conventional therapy devices. Following unfavorable clinical results with fast neutron therapy in the late 1930's andmore » early 1940's, the role of cyclotron produced fast neutrons is presently experiencing a renewal in radiation therapy. Several facilities are also experimenting with heavy charged particle beams for therapy.« less

Subwavelength micropillar array terahertz lasers.

PubMed

Krall, Michael; Brandstetter, Martin; Deutsch, Christoph; Detz, Hermann; Andrews, Aaron Maxwell; Schrenk, Werner; Strasser, Gottfried; Unterrainer, Karl

2014-01-13

We report on micropillar-based terahertz lasers with active pillars that are much smaller than the emission wavelength. These micropillar array lasers correspond to scaled-down band-edge photonic crystal lasers forming an active photonic metamaterial. In contrast to photonic crystal lasers which use significantly larger pillar structures, lasing emission is not observed close to high-symmetry points in the photonic band diagram, but in the effective medium regime. We measure stimulated emission at 4 THz for micropillar array lasers with pillar diameters of 5 µm. Our results not only demonstrate the integration of active subwavelength optics in a terahertz laser, but are also an important step towards the realization of nanowire-based terahertz lasers.

Wide field-of-view, multi-region two-photon imaging of neuronal activity in the mammalian brain

PubMed Central

Stirman, Jeffrey N.; Smith, Ikuko T.; Kudenov, Michael W.; Smith, Spencer L.

2016-01-01

Two-photon calcium imaging provides an optical readout of neuronal activity in populations of neurons with subcellular resolution. However, conventional two-photon imaging systems are limited in their field of view to ~1 mm2, precluding the visualization of multiple cortical areas simultaneously. Here, we demonstrate a two-photon microscope with an expanded field of view (>9.5 mm2) for rapidly reconfigurable simultaneous scanning of widely separated populations of neurons. We custom designed and assembled an optimized scan engine, objective, and two independently positionable, temporally multiplexed excitation pathways. We used this new microscope to measure activity correlations between two cortical visual areas in mice during visual processing. PMID:27347754

Towards telecommunication payloads with photonic technologies

NASA Astrophysics Data System (ADS)

Vono, S.; Di Paolo, G.; Piccinni, M.; Pisano, A.; Sotom, M.; Aveline, M.; Ginestet, P.

2017-11-01

In the last decade, Thales Alenia Space has put a lot of its research effort on Photonic Technologies for Space Application with the aim to offer the market satellite telecommunication systems better performance and lower costs. This research effort has been concentrated on several activities, some of them sponsored by ESA. Most promising applications refer to Payload Systems. In particular, photonic payload applications have been investigated through the following two ESA studies: Artes-1 "Next Generation Telecommunication Payloads based on Photonic Technologies" and Artes-5 "OWR - Optical Wideband Receiver" activities.

Photons for Therapy: Targeted Photodynamic Therapy for Infected and Contaminated Wounds

DTIC Science & Technology

2004-09-01

caused by Staphylococcus aureus that had been allowed to grow in abscesses below the skin. Conjugate injected into the infected area together with...16] these authors showed that several strains responsible for periodontal disease were efficiently inactivated by visible light irradiation in the...counting. Rocchetta et al studied the growth of bioluminescent E. coli in the neutropenic mouse-thigh abscess model of infection [25]. They found that

Optical dosimetry of radiotherapy beams using Cherenkov radiation: the relationship between light emission and dose.

PubMed

Glaser, Adam K; Zhang, Rongxiao; Gladstone, David J; Pogue, Brian W

2014-07-21

Recent studies have proposed that light emitted by the Cherenkov effect may be used for a number of radiation therapy dosimetry applications. There is a correlation between the captured light and expected dose under certain conditions, yet discrepancies have also been observed and a complete examination of the theoretical differences has not been done. In this study, a fundamental comparison between the Cherenkov emission and absorbed dose was explored for x-ray photons, electrons, and protons using both a theoretical and Monte Carlo-based analysis. Based on the findings of where dose correlates with Cherenkov emission, it was concluded that for x-ray photons the light emission would be optimally suited for narrow beam stereotactic radiation therapy and surgery validation studies, for verification of dynamic intensity-modulated and volumetric modulated arc therapy treatment plans in water tanks, near monoenergetic sources (e.g., Co-60 and brachy therapy sources) and also for entrance and exit surface imaging dosimetry of both narrow and broad beams. For electron use, Cherenkov emission was found to be only suitable for surface dosimetry applications. Finally, for proton dosimetry, there exists a fundamental lack of Cherenkov emission at the Bragg peak, making the technique of little use, although post-irradiation detection of light emission from radioisotopes could prove to be useful.

Mitochondria-targeting for improved photodynamic therapy

NASA Astrophysics Data System (ADS)

Ngen, Ethel J.

Photodynamic therapy (PDT) is an emerging cancer therapeutic modality, with great potential to selectively treat surface cancers, thus minimizing systemic side effects. In this dissertation, two approaches to deliver photosensitizers to mitochondria were investigated: 1) Reducing photosensitizer sizes to improve endocytosis and lysosomal localization. Upon irradiation the photosensitizers would then produce singlet oxygen which could rupture the lysosomal membrane releasing the lysosomally trapped photosensitizers to the cytosol, from where they could relocalize to mitochondria by passive diffusion (photochemical internalization). 2) Using delocalized lipophilic cationic dyes (DLCs) to exploit membrane potential differences between the cytoplasm and mitochondria in delivering photosensitizers to mitochondria. To investigate the effects of steric hindrance on mitochondrial localization and photodynamic response, a series of eight thiaporphyrins were studied. Two new thiaporphyrin analogues 6 and 8 with reduced steric hindrance at the 10- and 15- meso positions were studied in comparison to 5,20-diphenyl-10,15-bis[4 (carboxymethyleneoxy)-phenyl]-21,23-dithiaporphyrin 1, previously validated as a potential second generation photosensitizer. Although 6 showed an extraordinarily high uptake (7.6 times higher than 1), it was less potent than 1 (IC 50 = 0.18 muM versus 0.13 muM) even though they both showed similar sub-cellular localization patterns. This low potency was attributed to its high aggregation tendency in aqueous media (4 times higher than 1), which might have affected its ability to generate singlet oxygen in vitro . 8 on the other hand showed an even lower potency than 6 (2.28 vs 0.18 muM). However this was attributed to its low cellular uptake (20 times less than 6) and inefficient generation of singlet oxygen. Overall, although the structural modifications did improve the cellular uptake of 6, 6 was still less potent than the lead photosensitizers 1. Thus, other strategies to target mitochondria for improved photodynamic activity were investigated. In a continuing project, we evaluated the ability of delocalized lipophilic cationic dyes to deliver photosensitizers to mitochondria by exploiting the membrane potential difference between the cytoplasm and mitochondria. Two conjugates: a porphyrin--rhodamine B conjugate (TPP--Rh) and a porphyrin-acridine orange conjugate (TPP--AO), each possessing a single delocalized lipophilic cation, were designed and synthesized. The conjugates were synthesized by conjugating a monohydroxy porphyrin (TPP-OH) to rhodamine B (Rh B) and acridine orange base (AO), respectively, via saturated hydrocarbon linkers. To evaluate the efficiency of the conjugates as photosensitizers, their photophysical properties and in vitro photodynamic activities were studied in comparison to those of TPP-OH, the parent porphyrin photosensitizer. Although fluorescence energy transfer (FRET) was observed in the conjugates, they were capable of generating singlet oxygen at rates comparable to TPP-OH. In a final project, we evaluated the photophysical potential of TPP-Rh to act as a two-photon photosensitizer for PDT. Two-photon PDT is a rational approach used to improve light penetration through the skin. Rhodamine B is an effective two-photon chromophore and could significantly improve the two-photon absorption of the porphyrin photosensitizer in the TPP-Rh dyad system following energy transfer. Thus the porphyrin--rhodamine B dyad (TPP--Rh), previously demonstrated to preferentially accumulate in the mitochondria, was photophysically evaluated as a potential two-photon photosensitizer. To evaluate the efficiency of TPP-Rh as a two-photon photosensitizer, its two-photon photophysical properties were compared with those of its individual components (Rh B and TPP-OH). This included: the two-photon cross sections (sigma 2), RET kinetics and dynamics and rates of singlet oxygen generation. A FRET efficiency of ~99 % was observed from the Rh moiety (donor) to the TPP moiety (acceptor) of the system. This significantly enhanced the sigma 2 of TPP-Rh by ˜ 100 % (20 GM) compared to the parent TPP-OH. Furthermore, TPP-Rh produced singlet oxygen at a significantly faster rate than TPP-OH upon two-photon excitation. Thus, this indicates that conjugating photosensitizers to Rh B via short saturated hydrocarbon linkers could provide deeper tissue penetration, in addition to preferential mitochondrial accumulation for improved photodynamic response. (Abstract shortened by UMI.)

TiO2 activity enhancement through synergistic effect of photons localization of photonic crystals and the sensitization of CdS quantum dots

NASA Astrophysics Data System (ADS)

Li, Ping; Wang, Yuan; Wang, Ai-Jun; Chen, Sheng-Li

2017-02-01

In this work, the enhancement of TiO2 photocatalytic activity was studied through synergistic effect of the photons localization of photonic crystals and the sensitization of CdS quantum dots (CdS QDs). CdS QDs sensitized TiO2 membrane (denoted as CdS QDs/TiO2) was synthesized through doping the TiO2 membrane with CdS QDs by chemical bath deposition method (CBD). After TiO2 was sensitized with CdS QDs, the edge of light absorption of TiO2 was red-shifted to 470 nm and the light absorption in the range of 400 600 nm was higher than that of plain TiO2 membrane. Another type of composite membrane, CdS QDs/TiO2/SiO2 opal composite membrane was prepared by coupling SiO2 opal (a kind of photonic crystal) layer onto the CdS QDs/TiO2 membrane, and the photonic band gap of the SiO2 opal photonic crystal layer was deliberately planned at the electronic band gap of the CdS QDs. The photodegradation of gaseous CH3CHO (acetaldehyde) was used as probe reaction to test the photocatalytic activity of the as-prepared membranes, and the results showed that the CdS QDs sensitization can significantly improve the photocatalytic activity of TiO2 membrane under visible light irradiation, with the acetaldehyde degradation rate constant (k) on CdS QDs/TiO2 membranes being 1.59 times of that on plain TiO2 membranes. The acetaldehyde degradation rate constant on CdS QDs/TiO2/SiO2 opal composite membrane reached 4 times of that on plain TiO2 membrane. The photocatalytic activity of TiO2 membrane can be improved through synergistic effect of the photons localization of photonic crystals and the sensitization of CdS QDs.

Fast simulation of yttrium-90 bremsstrahlung photons with GATE.

PubMed

Rault, Erwann; Staelens, Steven; Van Holen, Roel; De Beenhouwer, Jan; Vandenberghe, Stefaan

2010-06-01

Multiple investigators have recently reported the use of yttrium-90 (90Y) bremsstrahlung single photon emission computed tomography (SPECT) imaging for the dosimetry of targeted radionuclide therapies. Because Monte Carlo (MC) simulations are useful for studying SPECT imaging, this study investigates the MC simulation of 90Y bremsstrahlung photons in SPECT. To overcome the computationally expensive simulation of electrons, the authors propose a fast way to simulate the emission of 90Y bremsstrahlung photons based on prerecorded bremsstrahlung photon probability density functions (PDFs). The accuracy of bremsstrahlung photon simulation is evaluated in two steps. First, the validity of the fast bremsstrahlung photon generator is checked. To that end, fast and analog simulations of photons emitted from a 90Y point source in a water phantom are compared. The same setup is then used to verify the accuracy of the bremsstrahlung photon simulations, comparing the results obtained with PDFs generated from both simulated and measured data to measurements. In both cases, the energy spectra and point spread functions of the photons detected in a scintillation camera are used. Results show that the fast simulation method is responsible for a 5% overestimation of the low-energy fluence (below 75 keV) of the bremsstrahlung photons detected using a scintillation camera. The spatial distribution of the detected photons is, however, accurately reproduced with the fast method and a computational acceleration of approximately 17-fold is achieved. When measured PDFs are used in the simulations, the simulated energy spectrum of photons emitted from a point source of 90Y in a water phantom and detected in a scintillation camera closely approximates the measured spectrum. The PSF of the photons imaged in the 50-300 keV energy window is also accurately estimated with a 12.4% underestimation of the full width at half maximum and 4.5% underestimation of the full width at tenth maximum. Despite its limited accuracy, the fast bremsstrahlung photon generator is well suited for the simulation of bremsstrahlung photons emitted in large homogeneous organs, such as the liver, and detected in a scintillation camera. The computational acceleration makes it very useful for future investigations of 90Y bremsstrahlung SPECT imaging.

Note: Large active area solid state photon counter with 20 ps timing resolution and 60 fs detection delay stability

NASA Astrophysics Data System (ADS)

Prochazka, Ivan; Kodet, Jan; Eckl, Johann; Blazej, Josef

2017-10-01

We are reporting on the design, construction, and performance of a photon counting detector system, which is based on single photon avalanche diode detector technology. This photon counting device has been optimized for very high timing resolution and stability of its detection delay. The foreseen application of this detector is laser ranging of space objects, laser time transfer ground to space and fundamental metrology. The single photon avalanche diode structure, manufactured on silicon using K14 technology, is used as a sensor. The active area of the sensor is circular with 200 μm diameter. Its photon detection probability exceeds 40% in the wavelength range spanning from 500 to 800 nm. The sensor is operated in active quenching and gating mode. A new control circuit was optimized to maintain high timing resolution and detection delay stability. In connection to this circuit, timing resolution of the detector is reaching 20 ps FWHM. In addition, the temperature change of the detection delay is as low as 70 fs/K. As a result, the detection delay stability of the device is exceptional: expressed in the form of time deviation, detection delay stability of better than 60 fs has been achieved. Considering the large active area aperture of the detector, this is, to our knowledge, the best timing performance reported for a solid state photon counting detector so far.

Iodine kinetics and dosimetry in the salivary glands during repeated courses of radioiodine therapy for thyroid cancer

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

Liu, B.; Huang, R.; Kuang, A.

2011-10-15

Purpose: The present study was conducted to investigate salivary iodine kinetics and dosimetry during repeated courses of radioiodine ({sup 131}I) therapy for differentiated thyroid cancer (DTC). Such data could provide a better understanding of the mechanisms of {sup 131}I induced salivary toxicity and help to develop appropriate methods to reduce this injury. Methods: Seventy-eight consecutive DTC patients (mean age 45 {+-} 17 years, 60%, female) undergoing {sup 131}I therapy for remnant ablation or metastatic tumors were prospectively recruited. Planar quantitative scintigraphy of head-neck images was serially acquired after administration of 2.9-7.4 GBq of {sup 131}I to assess kinetics in themore » salivary glands of patients. Salivary absorbed doses were calculated based on the schema of Medical Internal Radiation Dosimetry. Results: The maximum uptakes in percentage of administered {sup 131}I activity per kilogram of gland tissue (%/kg) were 12.9% {+-} 6.5%/kg (range, 0.4%-37.3%/kg) and 12.3% {+-} 6.2%/kg (range, 0.4%-35.1%/kg) for the parotid and submandibular glands, respectively. Statistically significant correlations of maximum uptake versus cumulative activity (r = -0.74, P < 0.01, for the parotid glands; r = -0.71, P < 0.01, for the submandibular glands) and treatment cycle (P < 0.001, for both gland types) were found. The effective half-lives of {sup 131}I in the parotid and submandibular glands were 9.3 {+-} 3.5 h (range, 1.5-19.8 h) and 8.6 {+-} 3.2 h (range, 0.8-18.0 h), respectively. A statistically significant correlation was observed between effective half-life with cumulative activity (r = 0.37, P < 0.01) and treatment cycle (P = 0.03) only for the parotid glands. The calculated absorbed doses were 0.20 {+-} 0.10 mGy/MBq (range, 0.01-0.92 mGy/MBq) and 0.25 {+-} 0.09 mGy/MBq (range, 0.01-1.52 mGy/MBq) for the parotid and submandibular glands, respectively. The photon contribution to the salivary absorbed dose was minimal in relation to the beta dose contribution. Photon-absorbed dose fractions of total absorbed dose were 4.9% {+-} 1.3% (range, 1.1%-8.7%) and 3.7% {+-} 2.5% (range, 0.8%-7.9%) for the parotid and submandibular glands, respectively. Conclusions: The iodine uptake of salivary glands is continuously reduced during the courses of therapy. The phenomenon of hyper-radiosensitivity may to some extent account for the occurrence of salivary gland hypofunction at very low radiation doses with low dose rates in {sup 131}I therapy. On the other hand, failure to incorporate a nonuniform and preferential uptake by salivary gland ductal cells may result in underestimating the actual dose for the critical tissue. Other methods, including {sup 124}I voxel-based dosimetry, are warranted to further investigate the {sup 131}I-induced salivary gland toxicity.« less

Apparatus for photon activation positron annihilation analysis

DOEpatents

Akers, Douglas W [Idaho Falls, ID

2007-06-12

Non-destructive testing apparatus according to one embodiment of the invention comprises a photon source. The photon source produces photons having predetermined energies and directs the photons toward a specimen being tested. The photons from the photon source result in the creation of positrons within the specimen being tested. A detector positioned adjacent the specimen being tested detects gamma rays produced by annihilation of positrons with electrons. A data processing system operatively associated with the detector produces output data indicative of a lattice characteristic of the specimen being tested.

Patterns of Failure After Proton Therapy in Medulloblastoma; Linear Energy Transfer Distributions and Relative Biological Effectiveness Associations for Relapses

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

Sethi, Roshan V.; Giantsoudi, Drosoula; Raiford, Michael

2014-03-01

Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine themore » LET and RBE values in areas of recurrence. Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy.« less

Quantitative evaluation of redox ratio and collagen characteristics during breast cancer chemotherapy using two-photon intrinsic imaging.

PubMed

Wu, Shulian; Huang, Yudian; Tang, Qinggong; Li, Zhifang; Horng, Hannah; Li, Jiatian; Wu, Zaihua; Chen, Yu; Li, Hui

2018-03-01

Preoperative neoadjuvant treatment in locally advanced breast cancer is recognized as an effective adjuvant therapy, as it improves treatment outcomes. However, the potential complications remain a threat, so there is an urgent clinical need to assess both the tumor response and changes in its microenvironment using non-invasive and precise identification techniques. Here, two-photon microscopy was employed to detect morphological alterations in breast cancer progression and recession throughout chemotherapy. The changes in structure were analyzed based on the autofluorescence and collagen of differing statuses. Parameters, including optical redox ratio, the ratio of second harmonic generation and auto-fluorescence signal, collagen density, and collagen shape orientation, were studied. Results indicate that these parameters are potential indicators for evaluating breast tumors and their microenvironment changes during progression and chemotherapy. Combined analyses of these parameters could provide a quantitative, novel method for monitoring tumor therapy.

Optical Imaging of Ionizing Radiation from Clinical Sources.

PubMed

Shaffer, Travis M; Drain, Charles Michael; Grimm, Jan

2016-11-01

Nuclear medicine uses ionizing radiation for both in vivo diagnosis and therapy. Ionizing radiation comes from a variety of sources, including x-rays, beam therapy, brachytherapy, and various injected radionuclides. Although PET and SPECT remain clinical mainstays, optical readouts of ionizing radiation offer numerous benefits and complement these standard techniques. Furthermore, for ionizing radiation sources that cannot be imaged using these standard techniques, optical imaging offers a unique imaging alternative. This article reviews optical imaging of both radionuclide- and beam-based ionizing radiation from high-energy photons and charged particles through mechanisms including radioluminescence, Cerenkov luminescence, and scintillation. Therapeutically, these visible photons have been combined with photodynamic therapeutic agents preclinically for increasing therapeutic response at depths difficult to reach with external light sources. Last, new microscopy methods that allow single-cell optical imaging of radionuclides are reviewed. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Inspiration, imagination and implementation: International Year of Light activities of the Photonics Academy of Wales at Bangor (PAWB)

NASA Astrophysics Data System (ADS)

Davies, Ray; Shore, K. Alan

2016-09-01

Since the establishment of the Photonics Academy of Wales in 2005, several generations of participants have been encouraged to use their imagination in devising, designing and building novel photonics devices of benefit to society. In pursuing photonics projects within PAWB, the participants have gained a practical proficiency in photonics experimentation and photonics product design. The Photonics Academy of Wales @ Bangor ( PAWB) assumed responsibility for the coordination of a series of events in Wales, UK as part of global activities celebrating 2015 as the International Year of Light. PAWB has worked with several organisations and individuals to devise a programme of events which are focussed on conveying the significance of light and its technologies to a broad swathe of the population. These events take into account the bi-lingual nature of Wales with significant events being delivered in the Welsh language. Arrangement and delivery of the events has largely been undertaken on a voluntary basis albeit with some funding having been obtained from supportive bodies and organisations. The presentation will report on the events which were organised and also will present examples of novel photonics devices developed by students working with PAWB. Being aware of the importance of creating an on-going interest in the topics treated during the International Year of Light, some attention will also be given to legacy activities beyond 2015. A specific concern is the identification of effective mechanisms for engagement with photonics industry.

In vivo demonstration of enhanced radiotherapy using rare earth doped titania nanoparticles.

PubMed

Townley, Helen E; Kim, Jeewon; Dobson, Peter J

2012-08-21

Radiation therapy is often limited by damage to healthy tissue and associated side-effects; restricting radiation to ineffective doses. Preferential incorporation of materials into tumour tissue can enhance the effect of radiation. Titania has precedent for use in photodynamic therapy (PDT), generating reactive oxygen species (ROS) upon photoexcitation, but is limited by the penetration depth of UV light. Optimization of a nanomaterial for interaction with X-rays could be used for deep tumour treatment. As such, titania nanoparticles were doped with gadolinium to optimize the localized energy absorption from a conventional medical X-ray, and further optimized by the addition of other rare earth (RE) elements. These elements were selected due to their large X-ray photon interaction cross-section, and potential for integration into the titania crystal structure. Specific activation of the nanoparticles by X-ray can result in generation of ROS leading to cell death in a tumour-localized manner. We show here that intratumoural injection of RE doped titania nanoparticles can enhance the efficacy of radiotherapy in vivo.

Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials

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

Mishra, Mark V., E-mail: mmishra@umm.edu; Aggarwal, Sameer; Bentzen, Soren M.

Purpose: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps. Methods and Materials: Active PBT clinical trials were identified from (clinicaltrials.gov) and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted. Results: A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% ofmore » trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy. Conclusions: The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities.« less

Simultaneous two-photon imaging and two-photon optogenetics of cortical circuits in three dimensions

PubMed Central

Carrillo-Reid, Luis; Bando, Yuki; Peterka, Darcy S

2018-01-01

The simultaneous imaging and manipulating of neural activity could enable the functional dissection of neural circuits. Here we have combined two-photon optogenetics with simultaneous volumetric two-photon calcium imaging to measure and manipulate neural activity in mouse neocortex in vivo in three-dimensions (3D) with cellular resolution. Using a hybrid holographic approach, we simultaneously photostimulate more than 80 neurons over 150 μm in depth in layer 2/3 of the mouse visual cortex, while simultaneously imaging the activity of the surrounding neurons. We validate the usefulness of the method by photoactivating in 3D selected groups of interneurons, suppressing the response of nearby pyramidal neurons to visual stimuli in awake animals. Our all-optical approach could be used as a general platform to read and write neuronal activity. PMID:29412138

Calibration of Cherenkov detectors for monoenergetic photon imaging in active interrogation applications

NASA Astrophysics Data System (ADS)

Rose, P. B.; Erickson, A. S.

2015-11-01

Active interrogation of cargo containers using monoenergetic photons offers a rapid and low-dose approach to search for shielded special nuclear materials. Cherenkov detectors can be used for imaging of the cargo provided that gamma ray energies used in interrogation are well resolved, as the case in 11B(d,n-γ)12C reaction resulting in 4.4 MeV and 15.1 MeV photons. While an array of Cherenkov threshold detectors reduces low energy background from scatter while providing the ability of high contrast transmission imaging, thus confirming the presence of high-Z materials, these detectors require a special approach to energy calibration due to the lack of resolution. In this paper, we discuss the utility of Cherenkov detectors for active interrogation with monoenergetic photons as well as the results of computational and experimental studies of their energy calibration. The results of the studies with sources emitting monoenergetic photons as well as complex gamma ray spectrum sources, for example 232Th, show that calibration is possible as long as the energies of photons of interest are distinct.

Autoradiography imaging in targeted alpha therapy with Timepix detector.

PubMed

A L Darwish, Ruqaya; Staudacher, Alexander Hugo; Bezak, Eva; Brown, Michael Paul

2015-01-01

There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy.

Autoradiography Imaging in Targeted Alpha Therapy with Timepix Detector

PubMed Central

AL Darwish, Ruqaya; Staudacher, Alexander Hugo; Bezak, Eva; Brown, Michael Paul

2015-01-01

There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy. PMID:25688285

Metal artifacts in computed tomography for radiation therapy planning: dosimetric effects and impact of metal artifact reduction.

PubMed

Giantsoudi, Drosoula; De Man, Bruno; Verburg, Joost; Trofimov, Alexei; Jin, Yannan; Wang, Ge; Gjesteby, Lars; Paganetti, Harald

2017-04-21

A significant and increasing number of patients receiving radiation therapy present with metal objects close to, or even within, the treatment area, resulting in artifacts in computed tomography (CT) imaging, which is the most commonly used imaging method for treatment planning in radiation therapy. In the presence of metal implants, such as dental fillings in treatment of head-and-neck tumors, spinal stabilization implants in spinal or paraspinal treatment or hip replacements in prostate cancer treatments, the extreme photon absorption by the metal object leads to prominent image artifacts. Although current CT scanners include a series of correction steps for beam hardening, scattered radiation and noisy measurements, when metal implants exist within or close to the treatment area, these corrections do not suffice. CT metal artifacts affect negatively the treatment planning of radiation therapy either by causing difficulties to delineate the target volume or by reducing the dose calculation accuracy. Various metal artifact reduction (MAR) methods have been explored in terms of improvement of organ delineation and dose calculation in radiation therapy treatment planning, depending on the type of radiation treatment and location of the metal implant and treatment site. Including a brief description of the available CT MAR methods that have been applied in radiation therapy, this article attempts to provide a comprehensive review on the dosimetric effect of the presence of CT metal artifacts in treatment planning, as reported in the literature, and the potential improvement suggested by different MAR approaches. The impact of artifacts on the treatment planning and delivery accuracy is discussed in the context of different modalities, such as photon external beam, brachytherapy and particle therapy, as well as by type and location of metal implants.

Metal artifacts in computed tomography for radiation therapy planning: dosimetric effects and impact of metal artifact reduction

NASA Astrophysics Data System (ADS)

Giantsoudi, Drosoula; De Man, Bruno; Verburg, Joost; Trofimov, Alexei; Jin, Yannan; Wang, Ge; Gjesteby, Lars; Paganetti, Harald

2017-04-01

A significant and increasing number of patients receiving radiation therapy present with metal objects close to, or even within, the treatment area, resulting in artifacts in computed tomography (CT) imaging, which is the most commonly used imaging method for treatment planning in radiation therapy. In the presence of metal implants, such as dental fillings in treatment of head-and-neck tumors, spinal stabilization implants in spinal or paraspinal treatment or hip replacements in prostate cancer treatments, the extreme photon absorption by the metal object leads to prominent image artifacts. Although current CT scanners include a series of correction steps for beam hardening, scattered radiation and noisy measurements, when metal implants exist within or close to the treatment area, these corrections do not suffice. CT metal artifacts affect negatively the treatment planning of radiation therapy either by causing difficulties to delineate the target volume or by reducing the dose calculation accuracy. Various metal artifact reduction (MAR) methods have been explored in terms of improvement of organ delineation and dose calculation in radiation therapy treatment planning, depending on the type of radiation treatment and location of the metal implant and treatment site. Including a brief description of the available CT MAR methods that have been applied in radiation therapy, this article attempts to provide a comprehensive review on the dosimetric effect of the presence of CT metal artifacts in treatment planning, as reported in the literature, and the potential improvement suggested by different MAR approaches. The impact of artifacts on the treatment planning and delivery accuracy is discussed in the context of different modalities, such as photon external beam, brachytherapy and particle therapy, as well as by type and location of metal implants.

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.

Fabrication and characterization of UV-emitting nanoparticles as novel radiation sensitizers targeting hypoxic tumor cells

NASA Astrophysics Data System (ADS)

Squillante, Michael R.; Jüstel, Thomas; Anderson, R. Rox; Brecher, Charles; Chartier, Daniel; Christian, James F.; Cicchetti, Nicholas; Espinoza, Sara; McAdams, Daniel R.; Müller, Matthias; Tornifoglio, Brooke; Wang, Yimin; Purschke, Martin

2018-06-01

Radiation therapy is one of the primary therapeutic techniques for treating cancer, administered to nearly two-thirds of all cancer patients. Although largely effective in killing cancer cells, radiation therapy, like other forms of cancer treatment, has difficulty dealing with hypoxic regions within solid tumors. The incomplete killing of cancer cells can lead to recurrence and relapse. The research presented here is investigating the enhancement of the efficacy of radiation therapy by using scintillating nanoparticles that emit UV photons. UV photons, with wavelengths between 230 nm and 280 nm, are able to inactivate cells due to their direct interaction with DNA, causing a variety of forms of damage. UV-emitting nanoparticles will enhance the treatment in two ways: first by generating UV photons in the immediate vicinity of cancer cells, leading to direct and oxygen-independent DNA damage, and second by down-converting the applied higher energy X-rays into softer X-rays and particles that are more efficiently absorbed in the targeted tumor region. The end result will be nanoparticles with a higher efficacy in the treatment of hypoxic cells in the tumor, filling an important, unmet clinical need. Our preliminary experiments show an increase in cell death using scintillating LuPO4:Pr nanoparticles over that achieved by the primary radiation alone. This work describes the fabrication of the nanoparticles, their physical characterization, and the spectroscopic characterization of the UV emission. The work also presents in vitro results that demonstrate an enhanced efficacy of cell killing with x-rays and a low unspecific toxicity of the nanoparticles.

Deep Inspiration Breath Hold—Based Radiation Therapy: A Clinical Review

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

Boda-Heggemann, Judit, E-mail: judit.boda-heggemann@umm.de; Knopf, Antje-Christin; Simeonova-Chergou, Anna

Several recent developments in linear accelerator–based radiation therapy (RT) such as fast multileaf collimators, accelerated intensity modulation paradigms like volumeric modulated arc therapy and flattening filter-free (FFF) high-dose-rate therapy have dramatically shortened the duration of treatment fractions. Deliverable photon dose distributions have approached physical complexity limits as a consequence of precise dose calculation algorithms and online 3-dimensional image guided patient positioning (image guided RT). Simultaneously, beam quality and treatment speed have continuously been improved in particle beam therapy, especially for scanned particle beams. Applying complex treatment plans with steep dose gradients requires strategies to mitigate and compensate for motion effectsmore » in general, particularly breathing motion. Intrafractional breathing-related motion results in uncertainties in dose delivery and thus in target coverage. As a consequence, generous margins have been used, which, in turn, increases exposure to organs at risk. Particle therapy, particularly with scanned beams, poses additional problems such as interplay effects and range uncertainties. Among advanced strategies to compensate breathing motion such as beam gating and tracking, deep inspiration breath hold (DIBH) gating is particularly advantageous in several respects, not only for hypofractionated, high single-dose stereotactic body RT of lung, liver, and upper abdominal lesions but also for normofractionated treatment of thoracic tumors such as lung cancer, mediastinal lymphomas, and breast cancer. This review provides an in-depth discussion of the rationale and technical implementation of DIBH gating for hypofractionated and normofractionated RT of intrathoracic and upper abdominal tumors in photon and proton RT.« less

Two-photon excited microscale colour centre patterns in Ag-activated phosphate glass written using a focused proton beam

NASA Astrophysics Data System (ADS)

Kurobori, Toshio; Kada, Wataru; Shirao, Taichi; Satoh, Takahiro

2018-02-01

We report a demonstration of microscale patterns in Ag-activated phosphate glass fabricated using a focused proton beam with an energy range of 1-3 MeV. Various microscale patterns are based on blue and orange radiophotoluminescent (RPL) centres. Two- and three-dimensional (2D and 3D) microstructures are visualised by combining two-photon confocal microscopy with femtosecond (fs) laser pulses generated from a mode-locked Ti:sapphire laser operating at 700 nm. The reconstructed images are analytically evaluated using lateral/axial dose mapping and RPL spectra. In addition, the advantages of two-photon excitation applied to Ag-activated phosphate glass are discussed, and this method is compared with single-photon excitation.

A critical appraisal of the clinical utility of proton therapy in oncology

PubMed Central

Wang, Dongxu

2015-01-01

Proton therapy is an emerging technology for providing radiation therapy to cancer patients. The depth dose distribution of a proton beam makes it a preferable radiation modality as it reduces radiation to the healthy tissue outside the tumor, compared with conventional photon therapy. While theoretically beneficial, its clinical values are still being demonstrated from the increasing number of patients treated with proton therapy, from several dozen proton therapy centers around the world. High equipment and facility costs are often the major obstacle for its wider adoption. Because of the high cost and lack of definite clinical evidence of its superiority, proton therapy treatment faces criticism on its cost-effectiveness. Technological development is causing a gradual lowering of costs, and research and clinical studies are providing further evidence on its clinical utility. PMID:26604838

Simulation with EGS4 code of external beam of radiotherapy apparatus with workstation and PC gives similar results?

PubMed

Malataras, G; Kappas, C; Lovelock, D M; Mohan, R

1997-01-01

This article presents a comparison between two implementations of an EGS4 Monte Carlo simulation of a radiation therapy machine. The first implementation was run on a high performance RISC workstation, and the second was run on an inexpensive PC. The simulation was performed using the MCRAD user code. The photon energy spectra, as measured at a plane transverse to the beam direction and containing the isocenter, were compared. The photons were also binned radially in order to compare the variation of the spectra with radius. With 500,000 photons recorded in each of the two simulations, the running times were 48 h and 116 h for the workstation and the PC, respectively. No significant statistical differences between the two implementations were found.

Heavy ion therapy: Bevalac epoch

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

Castro, J.R.

1993-10-01

An overview of heavy ion therapy at the Bevelac complex (SuperHILac linear accelerator + Bevatron) is given. Treatment planning, clinical results with helium ions on the skull base and uveal melanoma, clinical results with high-LET charged particles, neon radiotherapy of prostate cancer, heavy charged particle irradiation for unfavorable soft tissue sarcoma, preliminary results in heavy charged particle irradiation of bone sarcoma, and irradiation of bile duct carcinoma with charged particles and-or photons are all covered. (GHH)

Stochastic theory of photon flow in homogeneous and heterogeneous anisotropic biological and artificial material

NASA Astrophysics Data System (ADS)

Miller, Steven D.

1995-05-01

Standard Monte Carlo methods used in photon diffusion score absorbed photons or statistical weight deposited within voxels comprising a mesh. An alternative approach to a stochastic description is considered for rapid surface flux calculations and finite medias. Matrix elements are assigned to a spatial lattice whose function is to score vector intersections of scattered photons making transitions into either the forward or back solid angle half spaces. These complete matrix elements can be related to the directional fluxes within the lattice space. This model differentiates between ballistic, quasi-ballistic, and highly diffuse photon contributions, and effectively models the subsurface generation of a scattered light flux from a ballistic source. The connection between a path integral and diffusion is illustrated. Flux perturbations can be effectively illustrated for tissue-tumor-tissue and for 3 layer systems with strong absorption in one or more layers. For conditions where the diffusion theory has difficulties such as strong absorption, highly collimated sources, small finite volumes, and subsurface regions, the computation time of the algorithm is rapid with good accuracy and compliments other description of photon diffusion. The model has the potential to do computations relevant to photodynamic therapy (PDT) and analysis of laser beam interaction with tissues.

Dosimetric impact of a CT metal artefact suppression algorithm for proton, electron and photon therapies

NASA Astrophysics Data System (ADS)

Wei, Jikun; Sandison, George A.; Hsi, Wen-Chien; Ringor, Michael; Lu, Xiaoyi

2006-10-01

Accurate dose calculation is essential to precision radiation treatment planning and this accuracy depends upon anatomic and tissue electron density information. Modern treatment planning inhomogeneity corrections use x-ray CT images and calibrated scales of tissue CT number to electron density to provide this information. The presence of metal in the volume scanned by an x-ray CT scanner causes metal induced image artefacts that influence CT numbers and thereby introduce errors in the radiation dose distribution calculated. This paper investigates the dosimetric improvement achieved by a previously proposed x-ray CT metal artefact suppression technique when the suppressed images of a patient with bilateral hip prostheses are used in commercial treatment planning systems for proton, electron or photon therapies. For all these beam types, this clinical image and treatment planning study reveals that the target may be severely underdosed if a metal artefact-contaminated image is used for dose calculations instead of the artefact suppressed one. Of the three beam types studied, the metal artefact suppression is most important for proton therapy dose calculations, intermediate for electron therapy and least important for x-ray therapy but still significant. The study of a water phantom having a metal rod simulating a hip prosthesis indicates that CT numbers generated after image processing for metal artefact suppression are accurate and thus dose calculations based on the metal artefact suppressed images will be of high fidelity.

Engaging college physics students with photonics research

NASA Astrophysics Data System (ADS)

Adams, Rhys; Chen, Lawrence R.

2017-08-01

As educators and researchers in the field of photonics, we find what we do to be very exciting, and sharing this passion and excitement to our university students is natural to us. Via outreach programs and college research funding, a new college and university collaboration has broadened our student audience: photonics is brought into the college classroom and research opportunities are provided to college students. Photonics-themed active learning activities are conducted in the college Waves and Modern Physics class, helping students forge relationships between course content and modern communications technologies. Presentations on photonics research are prepared and presented by the professor and past college student-researchers. The students are then given a full tour of the photonics university laboratories. Furthermore, funds are set aside to give college students a unique opportunity to assist the college professor with experiments during a paid summer research internship.

Hypericin and pulsed laser therapy of squamous cell cancer in vitro.

PubMed

Bublik, Michael; Head, Christian; Benharash, Peyman; Paiva, Marcos; Eshraghi, Adrian; Kim, Taiho; Saxton, Romaine

2006-06-01

This in vitro study compares continuous wave and pulsed laser light at longer wavelengths for activation of the phototoxic drug hypericin in human cancer cells. Two-photon pulsed laser light now allows high-resolution fluorescent imaging of cancer cells and should provide deeper tissue penetration with near infrared light for improved detection as well as phototoxicity in human tumors. Cultured Seoul National University (SNU)-1 tumor cells from a squamous cell carcinoma (SCC) were incubated with hypericin before photoirradiation at four laser wavelengths. Phototoxicity of hypericin sensitized SCC cells was measured by dimethyl thiazoldiphenyl (MTT) tetrazolium bromide cell viability assays and by confocal fluorescence microscopy via 532-nm and infrared two-photon pulsed laser light. Phototoxic response increased linearly with hypericin dose of 0.1-2 microM, light exposure time of 5-120 sec, and pulsed dye laser wavelengths of 514-593 nm. Light energy delivery for 50% cell phototoxicity (LD50) response was 9 joules at 514 nm, 3 joules at 550 nm, and less than 1 joule at the 593 nm hypericin light absorption maxima. Fluorescence confocal microscopy revealed membrane and perinuclear localization of hypericin in the SNU cells with membrane damage seen after excitation with visible 532 nm continuous wave light or two-photon 700-950 nm picosecond pulsed laser irradiation. Hypericin may be a powerful tumor targetting drug when combined with pulsed laser light in patients with recurrent head and neck SCC.

Photofunctional triplet excited states of cyclometalated Ir(III) complexes: beyond electroluminescence.

PubMed

You, Youngmin; Nam, Wonwoo

2012-11-07

The development of cyclometalated Ir(III) complexes has enabled important breakthroughs in electroluminescence because such complexes permit the efficient population of triplet excited states that give rise to luminescent transitions. The triplet states of Ir(III) complexes are advantageous over those of other transition metal complexes in that their electronic transitions and charge-transfer characteristics are tunable over wide ranges. These favorable properties suggest that Ir(III) complexes have significant potential in a variety of photofunctions other than electroluminescence. In this critical review, we describe recent photonic applications of novel Ir(III) complexes. Ir(III) complexes have been shown to affect the exciton statistics in the active layers of organic photovoltaic cells, thereby improving the photon-to-current conversion efficiencies. Nonlinear optical applications that take advantage of the strong charge-transfer properties of triplet transitions are also discussed. The tunability of the electrochemical potentials facilitates the development of efficient photocatalysis in the context of water photolysis or organic syntheses. The photoredox reactivities of Ir(III) complexes have been employed in studies of charge migration along DNA chains. The photoinduced cytotoxicity of Ir(III) complexes on live cells suggests that the complexes may be useful in photodynamic therapy. Potential biological applications of the complexes include phosphorescence labeling and sensing. Intriguing platforms based on cyclometalated Ir(III) complexes potentially provide novel protein tagging and ratiometric detection. We envision that future research into the photofunctionality of Ir(III) complexes will provide important breakthroughs in a variety of photonic applications.

Electrothermally Driven Fluorescence Switching by Liquid Crystal Elastomers Based On Dimensional Photonic Crystals.

PubMed

Lin, Changxu; Jiang, Yin; Tao, Cheng-An; Yin, Xianpeng; Lan, Yue; Wang, Chen; Wang, Shiqiang; Liu, Xiangyang; Li, Guangtao

2017-04-05

In this article, the fabrication of an active organic-inorganic one-dimensional photonic crystal structure to offer electrothermal fluorescence switching is described. The film is obtained by spin-coating of liquid crystal elastomers (LCEs) and TiO 2 nanoparticles alternatively. By utilizing the property of LCEs that can change their size and shape reversibly under external thermal stimulations, the λ max of the photonic band gap of these films is tuned by voltage through electrothermal conversion. The shifted photonic band gap further changes the matching degree between the photonic band gap of the film and the emission spectrum of organic dye mounting on the film. With rhodamine B as an example, the enhancement factor of its fluorescence emission is controlled by varying the matching degree. Thus, the fluorescence intensity is actively switched by voltage applied on the system, in a fast, adjustable, and reversible manner. The control chain of using the electrothermal stimulus to adjust fluorescence intensity via controlling the photonic band gap is proved by a scanning electron microscope (SEM) and UV-vis reflectance. This mechanism also corresponded to the results from the finite-difference time-domain (FDTD) simulation. The comprehensive usage of photonic crystals and liquid crystal elastomers opened a new possibility for active optical devices.

WE-FG-BRA-12: Research Work of the Radio-Dynamic Treatment Mechanism

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

Zhang, Quanshi; Sun, Q.Y; Xiao, G.P.

2016-06-15

Purpose: The finite penetration depth of Laser light has limited clinical applications for PDT. This present work investigates the activation of photosensitizers using Cerenkov light emission from 45MV photon beams produced in an LA45 cancer therapy accelerator. We have named this new treatment technique Radio-Dynamic Therapy (RDT). Methods: Monte Carlo simulations were made on various Cerenkov emission energies and their spectroscopy in excited target areas in order to estimate their photosensitizer inner activation efficiency. The Cerenkov light excitation efficiency used in RDT has been theoretically compared with the exotic excitation efficiency of external Laser light used in PDT. In addition,more » laboratory tests showed the differences of the excitation efficiencies between a patented catalyst coenzyme added as a substrate, and then without the coenzyme. A specific probe of DMA (Singlet Oxygen fluorescent probe-9, 10-dimethylanthracene) was also used to detect singlet oxygen. Finally, we also compared our results with similar previous experimental work reported in the scientific literature. Results: Our Monte Carlo results showed that the Cerenkov light intensity induced with 45MV beams from an LA45 is 8 – 10 times the Cerenkov light intensity induced with 6MV beams from conventional accelerators. Furthermore, the patented catalyst coenzyme enhanced the excitation efficiency of photosensitizers by 3–6 times under different conditions. In clinical situations, the new RDT technique also showed favorable outcomes for early and late stages of specific cancers and it is also good at metastatic cancer treatment. Conclusion: Our results indicated that the process of using the Cerenkov light emission to excite photosensitizers from 45MV photons has a similar process and efficiency as the conventional laser in PDT. Comparing the advantages of RDT with a conventional PDT, the RDT may be developed into a potential treatment modality for a wider range of cancers stages as well as for other diseases.« less

Heterometallic Ru-Pt metallacycle for two-photon photodynamic therapy.

PubMed

Zhou, Zhixuan; Liu, Jiangping; Rees, Thomas W; Wang, Heng; Li, Xiaopeng; Chao, Hui; Stang, Peter J

2018-05-29

As an effective and noninvasive treatment of various diseases, photodynamic therapy (PTD) relies on the combination of light, a photosensitizer, and oxygen to generate cytotoxic reactive oxygen species that can damage malignant tissue. Much attention has been paid to covalent modifications of the photosensitizers to improve their photophysical properties and to optimize the pathway of the photosensitizers interacting with cells within the target tissue. Herein we report the design and synthesis of a supramolecular heterometallic Ru-Pt metallacycle via coordination-driven self-assembly. While inheriting the excellent photostability and two-photon absorption characteristics of the Ru(II) polypyridyl precursor, the metallacycle also exhibits red-shifted luminescence to the near-infrared region, a larger two-photon absorption cross-section, and higher singlet oxygen generation efficiency, making it an excellent candidate as a photosensitizer for PTD. Cellular studies reveal that the metallacycle selectively accumulates in mitochondria and nuclei upon internalization. As a result, singlet oxygen generated by photoexcitation of the metallacycle can efficiently trigger cell death via the simultaneous damage to mitochondrial function and intranuclear DNA. In vivo studies on tumor-bearing mice show that the metallacycle can efficiently inhibit tumor growth under a low light dose with minimal side effects. The supramolecular approach presented in this work provides a paradigm for the development of PDT agents with high efficacy.

A Nanosystem Capable of Releasing a Photosensitizer Bioprecursor under Two‐Photon Irradiation for Photodynamic Therapy

PubMed Central

Wu, Hao; Zeng, Fang; Zhang, Hang; Xu, Jiangsheng

2015-01-01

The applications of photodynamic therapy (PDT) are usually limited by photosensitizers' side effects and singlet oxygen's short half‐life. Herein, a mitochondria‐targeted nanosystem is demonstrated to enhance the PDT efficacy by releasing a bio‐precursor of photosensitizer under two‐photon irradiation. A phototriggerable coumarin derivative is first synthesized by linking 5‐aminolevulinic acid (5‐ALA, the bio‐precursor) to coumarin; and the nanosystem (CD‐ALA‐TPP) is then fabricated by covalently incorporating this coumarin derivative and a mitochondria‐targeting compound triphenylphosphonium (TPP) onto carbon dots (CDs). Upon cellular internalization, the nanosystem preferentially accumulates in mitochondria; and under one‐ or two‐photon irradiation, it releases 5‐ALA molecules that are then metabolized into protoporphyrin IX in mitochondria through a series of biosynthesis processes. The subsequent red light irradiation induces this endogenously synthesized photosensitizer to generate singlet oxygen, thereby causing oxidant damage to mitochondria and then the apoptosis of the cells. Analysis via 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyltetrazolium bromide (MTT) assays indicate that the novel PDT system exhibits enhanced cytotoxicity toward cancer cells. This study may offer a new strategy for designing PDT systems with high efficacy and low side effects. PMID:27774388

Enhancement of IUdR Radiosensitization by Low-Energy Photons Results from Increased and Persistent DNA Damage.

PubMed

Bayart, Emilie; Pouzoulet, Frédéric; Calmels, Lucie; Dadoun, Jonathan; Allot, Fabien; Plagnard, Johann; Ravanat, Jean-Luc; Bridier, André; Denozière, Marc; Bourhis, Jean; Deutsch, Eric

2017-01-01

Low-energy X-rays induce Auger cascades by photoelectric absorption in iodine present in the DNA of cells labeled with 5-iodo-2'-deoxyuridine (IUdR). This photoactivation therapy results in enhanced cellular sensitivity to radiation which reaches its maximum with 50 keV photons. Synchrotron core facilities are the only way to generate such monochromatic beams. However, these structures are not adapted for the routine treatment of patients. In this study, we generated two beams emitting photon energy means of 42 and 50 keV respectively, from a conventional 225 kV X-ray source. Viability assays performed after pre-exposure to 10 μM of IUdR for 48h suggest that complex lethal damage is generated after low energy photons irradiation compared to 137Cs irradiation (662KeV). To further decipher the molecular mechanisms leading to IUdR-mediated radiosensitization, we analyzed the content of DNA damage-induced foci in two glioblastoma cell lines and showed that the decrease in survival under these conditions was correlated with an increase in the content of DNA damage-induced foci in cell lines. Moreover, the follow-up of repair kinetics of the induced double-strand breaks showed the maximum delay in cells labeled with IUdR and exposed to X-ray irradiation. Thus, there appears to be a direct relationship between the reduction of radiation survival parameters and the production of DNA damage with impaired repair of these breaks. These results further support the clinical potential use of a halogenated pyrimidine analog combined with low-energy X-ray therapy.

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

SU-E-T-75: Commissioning Optically Stimulated Luminescence Dosimeters for Fast Neutron Therapy

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

Young, L; Yang, F; Sandison, G

Purpose: Fast neutrons therapy used at the University of Washington is clinically proven to be more effective than photon therapy in treating salivary gland and other cancers. A nanodot optically stimulated luminescence (OSL) system was chosen to be commissioned for patient in vivo dosimetry for neutron therapy. The OSL-based radiation detectors are not susceptible to radiation damage caused by neutrons compared to diodes or MOSFET systems. Methods: An In-Light microStar OSL system was commissioned for in vivo use by radiating Landauer nanodots with neutrons generated from 50.0 MeV protons accelerated onto a beryllium target. The OSLs were calibrated the depthmore » of maximum dose in solid water localized to 150 cm SAD isocenter in a 10.3 cm square field. Linearity was tested over a typical clinical dose fractionation range i.e. 0 to 150 neutron-cGy. Correction factors for transient signal fading, trap depletion, gantry angle, field size, and wedge factor dependencies were also evaluated. The OSLs were photo-bleached between radiations using a tungsten-halogen lamp. Results: Landauer sensitivity factors published for each nanodot are valid for measuring photon and electron doses but do not apply for neutron irradiation. Individually calculated nanodot calibration factors exhibited a 2–5% improvement over calibration factors computed by the microStar InLight software. Transient fading effects had a significant impact on neutron dose reading accuracy compared to photon and electron in vivo dosimetry. Greater accuracy can be achieved by calibrating and reading each dosimeter within 1–2 hours after irradiation. No additional OSL correction factors were needed for field size, gantry angle, or wedge factors in solid water phantom measurements. Conclusion: OSL detectors are a useful for neutron beam in vivo dosimetry verification. Dosimetric accuracy comparable to conventional diode systems can be achieved. Accounting for transient fading effects during the neutron beam calibration is a critical component for achieving comparable accuracy.« less

Using gEUD based plan analysis method to evaluate proton vs. photon plans for lung cancer radiation therapy.

PubMed

Xiao, Zhiyan; Zou, Wei J; Chen, Ting; Yue, Ning J; Jabbour, Salma K; Parikh, Rahul; Zhang, Miao

2018-03-01

The goal of this study was to exam the efficacy of current DVH based clinical guidelines draw from photon experience for lung cancer radiation therapy on proton therapy. Comparison proton plans and IMRT plans were generated for 10 lung patients treated in our proton facility. A gEUD based plan evaluation method was developed for plan evaluation. This evaluation method used normal lung gEUD(a) curve in which the model parameter "a" was sampled from the literature reported value. For all patients, the proton plans delivered lower normal lung V 5 Gy with similar V 20 Gy and similar target coverage. Based on current clinical guidelines, proton plans were ranked superior to IMRT plans for all 10 patients. However, the proton and IMRT normal lung gEUD(a) curves crossed for 8 patients within the tested range of "a", which means there was a possibility that proton plan would be worse than IMRT plan for lung sparing. A concept of deficiency index (DI) was introduced to quantify the probability of proton plans doing worse than IMRT plans. By applying threshold on DI, four patients' proton plan was ranked inferior to the IMRT plan. Meanwhile if a threshold to the location of curve crossing was applied, 6 patients' proton plan was ranked inferior to the IMRT plan. The contradictory ranking results between the current clinical guidelines and the gEUD(a) curve analysis demonstrated there is potential pitfalls by applying photon experience directly to the proton world. A comprehensive plan evaluation based on radio-biological models should be carried out to decide if a lung patient would really be benefit from proton therapy. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Inclusion of a variable RBE into proton and photon plan comparison for various fractionation schedules in prostate radiation therapy.

PubMed

Ödén, Jakob; Eriksson, Kjell; Toma-Dasu, Iuliana

2017-03-01

A constant relative biological effectiveness (RBE) of 1.1 is currently used in proton radiation therapy to account for the increased biological effectiveness compared to photon therapy. However, there is increasing evidence that proton RBE vary with the linear energy transfer (LET), the dose per fraction, and the type of the tissue. Therefore, this study aims to evaluate the impact of disregarding variations in RBE when comparing proton and photon dose plans for prostate treatments for various fractionation schedules using published RBE models and several α/β assumptions. Photon and proton dose plans were created for three generic prostate cancer cases. Three BED 3Gy equivalent schedules were studied, 78, 57.2, and 42.8 Gy in 39, 15, and 7 fractions, respectively. The proton plans were optimized assuming a constant RBE of 1.1. By using the Monte Carlo calculated dose-averaged LET (LET d ) distribution and assuming α/β values on voxel level, three variable RBE models were applied to the proton dose plans. The impact of the variable RBE was studied in the plan comparison, which was based on the dose distribution, DVHs, and normal tissue complication probabilities (NTCP) for the rectum. Subsequently, the physical proton dose was reoptimized for each proton plan based on the LET d distribution, to achieve a homogeneous RBE-weighted target dose when applying a specific RBE model and still fulfill the clinical goals for the rectum and bladder. All the photon and proton plans assuming RBE = 1.1 met the clinical goals with similar target coverage. The proton plans fulfilled the robustness criteria in terms of range and setup uncertainty. Applying the variable RBE models generally resulted in higher target doses and rectum NTCP compared to the photon plans. The increase was most pronounced for the fractionation dose of 2 Gy(RBE), whereas it was of less magnitude and more dependent on model and α/β assumption for the hypofractionated schedules. The reoptimized proton plans proved to be robust and showed similar target coverage and doses to the organs at risk as the proton plans optimized with a constant RBE. Model predicted RBE values may differ substantially from 1.1. This is most pronounced for fractionation doses of around 2 Gy(RBE) with higher doses to the target and the OARs, whereas the effect seems to be of less importance for the hypofractionated schedules. This could result in misleading conclusions when comparing proton plans to photon plans. By accounting for a variable RBE in the optimization process, robust and clinically acceptable dose plans, with the potential of lowering rectal NTCP, may be generated by reoptimizing the physical dose. However, the direction and magnitude of the changes in the physical proton dose to the prostate are dependent on RBE model and α/β assumptions and should therefore be used conservatively. © 2017 American Association of Physicists in Medicine.

More Adventures in Photodynamic Therapy.

PubMed

Kessel, David

2015-07-03

Photodynamic therapy is a procedure that can provide a selective eradication of neoplastic disease if sufficient drug, light, and oxygen are available. As this description suggests, it involves the photosensitization of malignant tissues to irradiation with photons in the visible range. While not suitable for tumors at unknown loci, it can be of use for eradication of cancer at surgical margins and therapy at sites where substantial surgery might otherwise be involved. Drug development has been delayed by several factors including the reluctance of major pharmaceutical firms in the United States to invest in this technology along with some unwise approaches in the past.

SU-E-T-263: Luminescent Dosimetry to Measure the Out-Of-Field Low and High LET Dose Components in High Energy Photon and Proton Therapy Beams.

PubMed

Reft, C

2012-06-01

Luminescent dosimetry using thermoluminescent detectors (TLDs) and optically stimulated luminescent detectors (OSLDs) were used in mixed radiation fields containing both low LET (photons and protons) and high LET (neutrons)components to obtain their out-of-field absorbed dose, dose equivalent and quality factor. LiF Thermoluminescent Detectors (TLDs) 600 and 700 chips with dimensions 0.31×0.31×0.038 cm 3 were used in a 25.4 cm diameter Bonner sphere centered 42 cm from the isocenter of a 15×x15 cm 2 field to measure the secondary doses for 10, 15 and 18 MV photons and a 200 MeV proton therapy beam. From the sensitivity difference to LET radiation between the210 and 280 C peaks in the glow curve, the areas under the peaks were used to obtain the absorbed dose, dose equivalent and QF of the secondary radiation. The OSLD detector measured the low LET dose component to compare with the TLD dose measurement. The neutron calibration of the TLDs was obtained from an Am-Be source at the Argonne National Laboratory. The photon and proton TLD and OSLD calibrations were obtained in 6 MV and 200 MeV beams, respectively. From the two-peak analysis of the TLDs in the Bonner sphere the ratios of the neutron dose to photon dose were 0.001, 0.014 and 0.17 for 10, 15 and 18 MV, respectively. The low LET OSLD measurements agreed within 10% of the TLD results. From the dose equivalent measurements the QFs (+/-14%) obtained were 4.5, 3.9 and 4.0 for these beam energies. For the 200 MeV proton beam the ratio of neutron to proton dose was 0.28 with a measured QF of 13. Luminescent detectors in a Bonner Sphere provide measurements of the secondary photon, proton and neutron doses and provide an estimate of the neutron QF. © 2012 American Association of Physicists in Medicine.

An Active Metamaterial Platform for Chiral Responsive Optoelectronics.

PubMed

Kang, Lei; Lan, Shoufeng; Cui, Yonghao; Rodrigues, Sean P; Liu, Yongmin; Werner, Douglas H; Cai, Wenshan

2015-08-05

Chiral-selective non-linear optics and optoelectronic signal generation are demonstrated in an electrically active photonic metamaterial. The metamaterial reveals significant chiroptical responses in both harmonic generation and the photon drag effect, correlated to the resonance behavior in the linear regime. The multifunctional chiral metamaterial with dual electrical and optical functionality enables transduction of chiroptical responses to electrical signals for integrated photonics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Robot-assisted motor activation monitored by time-domain optical brain imaging

NASA Astrophysics Data System (ADS)

Steinkellner, O.; Wabnitz, H.; Schmid, S.; Steingräber, R.; Schmidt, H.; Krüger, J.; Macdonald, R.

2011-07-01

Robot-assisted motor rehabilitation proved to be an effective supplement to conventional hand-to-hand therapy in stroke patients. In order to analyze and understand motor learning and performance during rehabilitation it is desirable to develop a monitor to provide objective measures of the corresponding brain activity at the rehabilitation progress. We used a portable time-domain near-infrared reflectometer to monitor the hemodynamic brain response to distal upper extremity activities. Four healthy volunteers performed two different robot-assisted wrist/forearm movements, flexion-extension and pronation-supination in comparison with an unassisted squeeze ball exercise. A special headgear with four optical measurement positions to include parts of the pre- and postcentral gyrus provided a good overlap with the expected activation areas. Data analysis based on variance of time-of-flight distributions of photons through tissue was chosen to provide a suitable representation of intracerebral signals. In all subjects several of the four detection channels showed a response. In some cases indications were found of differences in localization of the activated areas for the various tasks.

Iron oxide and gold nanoparticles in cancer therapy

NASA Astrophysics Data System (ADS)

Gotman, Irena; Psakhie, Sergey G.; Lozhkomoev, Aleksandr S.; Gutmanas, Elazar Y.

2016-08-01

Continuous research activities in the field of nanomedicine in the past decade have, to a great extent, been focused on nanoparticle technologies for cancer therapy. Gold and iron oxide nanoparticles (NP) are two of the most studied inorganic nanomaterials due to their unique optical and magnetic properties. Both types of NPs are emerging as promising systems for anti-tumor drug delivery and for nanoparticle-mediated thermal therapy of cancer. In thermal therapy, localized heating inside tumors or in proximity of tumor cells can be induced, for example, with Au NPs by radiofrequency ablation heating or conversion of photon energy (photothermal therapy) and in iron oxide magnetic NPs by heat generation through relaxation in an alternating magnetic field (magnetic hyperthermia). Furthermore, the superparamagnetic properties of iron oxide nanoparticles have led to their use as potent MRI (magnetic resonance imaging) contrast agents. Surface modification/coating can produce NPs with tailored and desired properties, such as enhanced blood circulation time, stability, biocompatibility and water solubility. To target nanoparticles to specific tumor cells, NPs should be conjugated with targeting moieties on the surface which bind to receptors or other molecular structures on the cell surface. The article presents several approaches to enhancing the specificity of Au and iron oxide nanoparticles for tumor tissue by appropriate surface modification/functionalization, as well as the effect of these treatments on the saturation magnetization value of iron oxide NPs. The use of other nanoparticles and nanostructures in cancer treatment is also briefly reviewed.

Ionizing radiation-induced acoustics for radiotherapy and diagnostic radiology applications.

PubMed

Hickling, Susannah; Xiang, Liangzhong; Jones, Kevin C; Parodi, Katia; Assmann, Walter; Avery, Stephen; Hobson, Maritza; El Naqa, Issam

2018-04-21

Acoustic waves are induced via the thermoacoustic effect in objects exposed to a pulsed beam of ionizing radiation. This phenomenon has interesting potential applications in both radiotherapy dosimetry and treatment guidance as well as low dose radiological imaging. After initial work in the field in the 1980s and early 1990s, little research was done until 2013 when interest was rejuvenated, spurred on by technological advances in ultrasound transducers and the increasing complexity of radiotherapy delivery systems. Since then, many studies have been conducted and published applying ionizing radiation-induced acoustic principles into three primary research areas: Linear accelerator photon beam dosimetry, proton therapy range verification, and radiological imaging. This review article introduces the theoretical background behind ionizing radiation-induced acoustic waves, summarizes recent advances in the field, and provides an outlook on how the detection of ionizing radiation-induced acoustic waves can be used for relative and in vivo dosimetry in photon therapy, localization of the Bragg peak in proton therapy, and as a low-dose medical imaging modality. Future prospects and challenges for clinical implementation of these techniques are discussed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Dose specification for radiation therapy: dose to water or dose to medium?

NASA Astrophysics Data System (ADS)

Ma, C.-M.; Li, Jinsheng

2011-05-01

The Monte Carlo method enables accurate dose calculation for radiation therapy treatment planning and has been implemented in some commercial treatment planning systems. Unlike conventional dose calculation algorithms that provide patient dose information in terms of dose to water with variable electron density, the Monte Carlo method calculates the energy deposition in different media and expresses dose to a medium. This paper discusses the differences in dose calculated using water with different electron densities and that calculated for different biological media and the clinical issues on dose specification including dose prescription and plan evaluation using dose to water and dose to medium. We will demonstrate that conventional photon dose calculation algorithms compute doses similar to those simulated by Monte Carlo using water with different electron densities, which are close (<4% differences) to doses to media but significantly different (up to 11%) from doses to water converted from doses to media following American Association of Physicists in Medicine (AAPM) Task Group 105 recommendations. Our results suggest that for consistency with previous radiation therapy experience Monte Carlo photon algorithms report dose to medium for radiotherapy dose prescription, treatment plan evaluation and treatment outcome analysis.

Dosimetric evaluation of a MOSFET detector for clinical application in photon therapy.

PubMed

Kohno, Ryosuke; Hirano, Eriko; Nishio, Teiji; Miyagishi, Tomoko; Goka, Tomonori; Kawashima, Mitsuhiko; Ogino, Takashi

2008-01-01

Dosimetric characteristics of a metal oxide-silicon semiconductor field effect transistor (MOSFET) detector are studied with megavoltage photon beams for patient dose verification. The major advantages of this detector are its size, which makes it a point dosimeter, and its ease of use. In order to use the MOSFET detector for dose verification of intensity-modulated radiation therapy (IMRT) and in-vivo dosimetry for radiation therapy, we need to evaluate the dosimetric properties of the MOSFET detector. Therefore, we investigated the reproducibility, dose-rate effect, accumulated-dose effect, angular dependence, and accuracy in tissue-maximum ratio measurements. Then, as it takes about 20 min in actual IMRT for the patient, we evaluated fading effect of MOSFET response. When the MOSFETs were read-out 20 min after irradiation, we observed a fading effect of 0.9% with 0.9% standard error of the mean. Further, we applied the MOSFET to the measurement of small field total scatter factor. The MOSFET for dose measurements of small field sizes was better than the reference pinpoint chamber with vertical direction. In conclusion, we assessed the accuracy, reliability, and usefulness of the MOSFET detector in clinical applications such as pinpoint absolute dosimetry for small fields.

Development of an applicator for multiphoton PDT

NASA Astrophysics Data System (ADS)

Graschew, Georgi; Bastian, Matthias; Rakowsky, Stefan; Roelofs, Theo A.; Balanos, Evangelos; Schlag, Peter M.; Steinmeyer, Gunter; Elsaesser, Thomas

2004-09-01

Multiphoton excitation of photosensitizers for laser induced fluorescence diagnosis (LIFD) and photodynamic therapy (PDT) of tumors has the advantage of greater tissue penetration due to the longer wavelength of irradiation. However, multiphoton LIFD and PDT are presently not clinically applicable as there are no applicators available for the delivery of the pulsed laser radiation to the operating room. As an approach, in this contribution the beam delivery through photonic crystal fibers has been investigated. Pulses of a Ti:sapphire laser of 100 fs pulse duration and an average power of 150 mW have been transported through such a fiber of 25 m length and the resulting pulses show the absence of nonlinear contributions but still a broadening of the pulse to 2 ps due to the dispersion of the fiber. It is planned to compensate this broadening by a grating in front of the fiber. Alternatively, the transport of laser radiation of 150 fs and 100 mW through a mirror-joint-arm used for conventional CO2 lasers has been tested showing no broadening of the laser pulses. Two-photon photodynamic activity of mTHPC-CMPEG4 shall serve as a test of the laser light transport system.

Bowel sparing in pediatric cranio-spinal radiotherapy: a comparison of combined electron and photon and helical TomoTherapy techniques to a standard photon method

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

Harron, Elizabeth, E-mail: elizabeth.harron@nuh.nhs.uk; Lewis, Joanne

2012-07-01

The aim of this study was to compare the dose to organs at risk (OARs) from different craniospinal radiotherapy treatment approaches available at the Northern Centre for Cancer Care (NCCC), with a particular emphasis on sparing the bowel. Method: Treatment plans were produced for a pediatric medulloblastoma patient with inflammatory bowel disease using 3D conformal 6-MV photons (3DCP), combined 3D 6-MV photons and 18-MeV electrons (3DPE), and helical photon TomoTherapy (HT). The 3DPE plan was a modification of the standard 3DCP technique, using electrons to treat the spine inferior to the level of the diaphragm. The plans were compared inmore » terms of the dose-volume data to OARs and the nontumor integral dose. Results: The 3DPE plan was found to give the lowest dose to the bowel and the lowest nontumor integral dose of the 3 techniques. However, the coverage of the spine planning target volume (PTV) was least homogeneous using this technique, with only 74.6% of the PTV covered by 95% of the prescribed dose. HT was able to achieve the best coverage of the PTVs (99.0% of the whole-brain PTV and 93.1% of the spine PTV received 95% of the prescribed dose), but delivered a significantly higher integral dose. HT was able to spare the heart, thyroid, and eyes better than the linac-based techniques, but other OARs received a higher dose. Conclusions: Use of electrons was the best method for reducing the dose to the bowel and the integral dose, at the expense of compromised spine PTV coverage. For some patients, HT may be a viable method of improving dose homogeneity and reducing selected OAR doses.« less

New photosensitizers for photodynamic therapy

PubMed Central

Abrahamse, Heidi; Hamblin, Michael R.

2016-01-01

Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound. PMID:26862179

New photosensitizers for photodynamic therapy.

PubMed

Abrahamse, Heidi; Hamblin, Michael R

2016-02-15

Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound. © 2016 Authors; published by Portland Press Limited.

An investigation of the operating characteristics of two PTW diamond detectors in photon and electron beams.

PubMed

De Angelis, C; Onori, S; Pacilio, M; Cirrone, G A P; Cuttone, G; Raffaele, L; Bucciolini, M; Mazzocchi, S

2002-02-01

The dosimetric properties of two PTW Riga diamond detectors type 60003 were studied in high-energy photon and electron therapy beam. Properties under study were current-voltage characteristic, polarization effect, time stability of response, dose response, dose-rate dependence, temperature stability, and beam quality dependence of the sensitivity factor. Differences were shown between the two detectors for most of the previous properties. Also, the observed behavior was, to some extent, different from what was reported in the PTW technical specifications. The necessity to characterize each diamond detector individually was addressed.

Study of HeLa cells clone survival after X-ray irradiation in the presence of cisplatin

NASA Astrophysics Data System (ADS)

Baulin, A. A.; Sukhikh, E. S.; Vasilyev, S. A.; Sukhikh, L. G.; Sheino, I. N.

2017-09-01

Radiation therapy in the presence of heavy elements nuclei (Z > 53) is widely developed these days. The presence of such nuclei in cancer cells results in the local increase of energy release from primary photon beam thus increasing relative biological efficiency. In this paper we present the preliminary results of the cell survival study while irradiating cells by X-Ray photon beam in the presence of cisplatin (Pt, Z = 78). The preliminary results show the decrease of the cell survival in the presence of both radiation and cisplatin.

Two-dimensional silicon-based detectors for ion beam therapy

NASA Astrophysics Data System (ADS)

Martišíková, M.; Granja, C.; Jakůbek, J.; Hartmann, B.; Telsemeyer, J.; Huber, L.; Brons, S.; Pospíšil, S.; Jäkel, O.

2012-02-01

Radiation therapy with ion beams is a highly precise kind of cancer treatment. As ion beams traverse material, the highest ionization density occurs at the end of their path. Due to this Bragg-peak, ion beams enable higher dose conformation to the tumor and increased sparing of the surrounding tissue, in comparison to standard radiation therapy using high energy photons. Ions heavier than protons offer in addition increased biological effectiveness and lower scattering. The Heidelberg Ion Beam Therapy Center (HIT) is a state-of-the-art ion beam therapy facility and the first hospital-based facility in Europe. It provides proton and carbon ion treatments. A synchrotron is used for ion acceleration. For dose delivery to the patient, narrow pencil-like beams are scanned over the target volume.

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

Comparative study of the calculated risk of radiation-induced cancer after photon- and proton-beam based radiosurgery of liver metastases.

PubMed

Mondlane, Gracinda; Gubanski, Michael; Lind, Pehr A; Ureba, Ana; Siegbahn, Albert

2017-10-01

The potential of proton therapy to improve the sparing of the healthy tissue has been demonstrated in several studies. However, even small doses delivered to the organs at risk (OAR) may induce long-term detriments after radiotherapy. In this study, we investigated the possibility to reduce the risk of radiation-induced secondary cancers with intensity modulated proton therapy (IMPT), when used for radiosurgery of liver metastases. Ten patients, previously treated for liver metastases with photon-beam based stereotactic body radiation therapy (SBRT) were retrospectively planned for radiosurgery with IMPT. A treatment plan comparison was then performed in terms of calculated risk of radiation-induced secondary cancer. The risks were estimated using two distinct models (Dasu et al., 2005; Schneider et al., 2005, 2009). The plans were compared pairwise with a two-sided Wilcoxon signed-rank test with a significance level of 0.05. Reduced risks for induction of fatal and other types of cancers were estimated for the IMPT plans (p<0.05) with the Dasu et al. Using the Schneider et al. model, lower risks for carcinoma-induction with IMPT were estimated for the skin, lungs, healthy part of the liver, esophagus and the remaining part of the body (p<0.05). The risk of observing sarcomas in the bone was also reduced with IMPT (p<0.05). The findings of this study indicate that the risks of radiation-induced secondary cancers after radiosurgery of liver metastases may be reduced, if IMPT is used instead of photon-beam based SBRT. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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.

Integrating nanostructured electrodes in organic photovoltaic devices for enhancing near-infrared photoresponse

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

Nardes, Alexandre M.; Ahn, Sungmo; Rourke, Devin

2016-12-01

We introduce a simple methodology to integrate prefabricated nanostructured-electrodes in solution-processed organic photovoltaic (OPV) devices. The tailored 'photonic electrode' nanostructure is used for light management in the device and for hole collection. This approach opens up new possibilities for designing photonically active structures that can enhance the absorption of sub-bandgap photons in the active layer. We discuss the design, fabrication and characterization of photonic electrodes, and the methodology for integrating them to OPV devices using a simple lamination technique. We demonstrate theoretically and experimentally that OPV devices using photonic electrodes show a factor of ca. 5 enhancement in external quantummore » efficiency (EQE) in the near infrared region. We use simulations to trace this observed efficiency enhancement to surface plasmon polariton modes in the nanostructure.« less

Quantum optics. All-optical routing of single photons by a one-atom switch controlled by a single photon.

PubMed

Shomroni, Itay; Rosenblum, Serge; Lovsky, Yulia; Bechler, Orel; Guendelman, Gabriel; Dayan, Barak

2014-08-22

The prospect of quantum networks, in which quantum information is carried by single photons in photonic circuits, has long been the driving force behind the effort to achieve all-optical routing of single photons. We realized a single-photon-activated switch capable of routing a photon from any of its two inputs to any of its two outputs. Our device is based on a single atom coupled to a fiber-coupled, chip-based microresonator. A single reflected control photon toggles the switch from high reflection (R ~ 65%) to high transmission (T ~ 90%), with an average of ~1.5 control photons per switching event (~3, including linear losses). No additional control fields are required. The control and target photons are both in-fiber and practically identical, making this scheme compatible with scalable architectures for quantum information processing. Copyright © 2014, American Association for the Advancement of Science.

Demonstration of glass-based photonic interposer for mid-board-optical engines and electrical-optical circuit board (EOCB) integration strategy

NASA Astrophysics Data System (ADS)

Schröder, H.; Neitz, M.; Schneider-Ramelow, M.

2018-02-01

Due to its optical transparency and superior dielectric properties glass is regarded as a promising candidate for advanced applications as active photonic interposer for mid-board-optics and optical PCB waveguide integration. The concepts for multi-mode and single-mode photonic system integration are discussed and related demonstration project results will be presented. A hybrid integrated photonic glass body interposer with integrated optical lenses for multi-mode data communication wavelength of 850 nm have been realized. The paper summarizes process developments which allow cost efficient metallization of TGV. Electro-optical elements like photodiodes and VCSELs can be directly flip-chip mounted on the glass substrate according to the desired lens positions. Furthermore results for a silicon photonic based single-mode active interposer integration onto a single mode glass made EOCB will be compared in terms of packaging challenges. The board level integration strategy for both of these technological approaches and general next generation board level integration concepts for photonic interposer will be introductorily discussed.

Evaluation of water-mimicking solid phantom materials for use in HDR and LDR brachytherapy dosimetry

NASA Astrophysics Data System (ADS)

Schoenfeld, Andreas A.; Thieben, Maike; Harder, Dietrich; Poppe, Björn; Chofor, Ndimofor

2017-12-01

In modern HDR or LDR brachytherapy with photon emitters, fast checks of the dose profiles generated in water or a water-equivalent phantom have to be available in the interest of patient safety. However, the commercially available brachytherapy photon sources cover a wide range of photon emission spectra, and the range of the in-phantom photon spectrum is further widened by Compton scattering, so that the achievement of water-mimicking properties of such phantoms involves high requirements on their atomic composition. In order to classify the degree of water equivalence of the numerous commercially available solid water-mimicking phantom materials and the energy ranges of their applicability, the radial profiles of the absorbed dose to water, D w, have been calculated using Monte Carlo simulations in these materials and in water phantoms of the same dimensions. This study includes the HDR therapy sources Nucletron Flexisource Co-60 HDR (60Co), Eckert und Ziegler BEBIG GmbH CSM-11 (137Cs), Implant Sciences Corporation HDR Yb-169 Source 4140 (169Yb) as well as the LDR therapy sources IsoRay Inc. Proxcelan CS-1 (131Cs), IsoAid Advantage I-125 IAI-125A (125I), and IsoAid Advantage Pd-103 IAPd-103A (103Pd). Thereby our previous comparison between phantom materials and water surrounding a Varian GammaMed Plus HDR therapy 192Ir source (Schoenfeld et al 2015) has been complemented. Simulations were performed in cylindrical phantoms consisting of either water or the materials RW1, RW3, Solid Water, HE Solid Water, Virtual Water, Plastic Water DT, Plastic Water LR, Original Plastic Water (2015), Plastic Water (1995), Blue Water, polyethylene, polystyrene and PMMA. While for 192Ir, 137Cs and 60Co most phantom materials can be regarded as water equivalent, for 169Yb the materials Plastic Water LR, Plastic Water DT and RW1 appear as water equivalent. For the low-energy sources 106Pd, 131Cs and 125I, only Plastic Water LR can be classified as water equivalent.

Prior image constrained image reconstruction in emerging computed tomography applications

NASA Astrophysics Data System (ADS)

Brunner, Stephen T.

Advances have been made in computed tomography (CT), especially in the past five years, by incorporating prior images into the image reconstruction process. In this dissertation, we investigate prior image constrained image reconstruction in three emerging CT applications: dual-energy CT, multi-energy photon-counting CT, and cone-beam CT in image-guided radiation therapy. First, we investigate the application of Prior Image Constrained Compressed Sensing (PICCS) in dual-energy CT, which has been called "one of the hottest research areas in CT." Phantom and animal studies are conducted using a state-of-the-art 64-slice GE Discovery 750 HD CT scanner to investigate the extent to which PICCS can enable radiation dose reduction in material density and virtual monochromatic imaging. Second, we extend the application of PICCS from dual-energy CT to multi-energy photon-counting CT, which has been called "one of the 12 topics in CT to be critical in the next decade." Numerical simulations are conducted to generate multiple energy bin images for a photon-counting CT acquisition and to investigate the extent to which PICCS can enable radiation dose efficiency improvement. Third, we investigate the performance of a newly proposed prior image constrained scatter correction technique to correct scatter-induced shading artifacts in cone-beam CT, which, when used in image-guided radiation therapy procedures, can assist in patient localization, and potentially, dose verification and adaptive radiation therapy. Phantom studies are conducted using a Varian 2100 EX system with an on-board imager to investigate the extent to which the prior image constrained scatter correction technique can mitigate scatter-induced shading artifacts in cone-beam CT. Results show that these prior image constrained image reconstruction techniques can reduce radiation dose in dual-energy CT by 50% in phantom and animal studies in material density and virtual monochromatic imaging, can lead to radiation dose efficiency improvement in multi-energy photon-counting CT, and can mitigate scatter-induced shading artifacts in cone-beam CT in full-fan and half-fan modes.

Evaluation of water-mimicking solid phantom materials for use in HDR and LDR brachytherapy dosimetry.

PubMed

Schoenfeld, Andreas A; Thieben, Maike; Harder, Dietrich; Poppe, Björn; Chofor, Ndimofor

2017-11-21

In modern HDR or LDR brachytherapy with photon emitters, fast checks of the dose profiles generated in water or a water-equivalent phantom have to be available in the interest of patient safety. However, the commercially available brachytherapy photon sources cover a wide range of photon emission spectra, and the range of the in-phantom photon spectrum is further widened by Compton scattering, so that the achievement of water-mimicking properties of such phantoms involves high requirements on their atomic composition. In order to classify the degree of water equivalence of the numerous commercially available solid water-mimicking phantom materials and the energy ranges of their applicability, the radial profiles of the absorbed dose to water, D w , have been calculated using Monte Carlo simulations in these materials and in water phantoms of the same dimensions. This study includes the HDR therapy sources Nucletron Flexisource Co-60 HDR ( 60 Co), Eckert und Ziegler BEBIG GmbH CSM-11 ( 137 Cs), Implant Sciences Corporation HDR Yb-169 Source 4140 ( 169 Yb) as well as the LDR therapy sources IsoRay Inc. Proxcelan CS-1 ( 131 Cs), IsoAid Advantage I-125 IAI-125A ( 125 I), and IsoAid Advantage Pd-103 IAPd-103A ( 103 Pd). Thereby our previous comparison between phantom materials and water surrounding a Varian GammaMed Plus HDR therapy 192 Ir source (Schoenfeld et al 2015) has been complemented. Simulations were performed in cylindrical phantoms consisting of either water or the materials RW1, RW3, Solid Water, HE Solid Water, Virtual Water, Plastic Water DT, Plastic Water LR, Original Plastic Water (2015), Plastic Water (1995), Blue Water, polyethylene, polystyrene and PMMA. While for 192 Ir, 137 Cs and 60 Co most phantom materials can be regarded as water equivalent, for 169 Yb the materials Plastic Water LR, Plastic Water DT and RW1 appear as water equivalent. For the low-energy sources 106 Pd, 131 Cs and 125 I, only Plastic Water LR can be classified as water equivalent.

Portal Connecting Dark Photons and Axions.

PubMed

Kaneta, Kunio; Lee, Hye-Sung; Yun, Seokhoon

2017-03-10

The dark photon and the axion (or axionlike particle) are popular light particles of the hidden sector. Each of them has been actively searched for through the couplings called the vector portal and the axion portal. We introduce a new portal connecting the dark photon and the axion (axion-photon-dark photon, axion-dark photon-dark photon), which emerges in the presence of the two particles. This dark axion portal is genuinely new couplings, not just from a product of the vector portal and the axion portal, because of the internal structure of these couplings. We present a simple model that realizes the dark axion portal and discuss why it warrants a rich phenomenology.

808-nm laser therapy with a flat-top handpiece photobiomodulates mitochondria activities of Paramecium primaurelia (Protozoa).

PubMed

Amaroli, Andrea; Ravera, Silvia; Parker, Steven; Panfoli, Isabella; Benedicenti, Alberico; Benedicenti, Stefano

2016-05-01

Photobiomodulation is proposed as a non-linear process, and only low-level laser therapy (LLLT) is assumed to stimulate exposed cells, whereas high powered laser and fluences can cause negative effects, exhausting the cell's energy reserve as a consequence of excessive photon-based stimulation. In our work, we investigated and compared the effects of 808-nm diode laser (CW) with a new flat-top handpiece. To this purpose, we tested the photobiomodulation effects of 1 and 3 J/cm(2) fluence, both generated by 100 mW or 1 W of laser power and of 64 J/cm(2) of fluence generated by 100 mW, 1 W, 1.5 W or 2 W, as expressed through oxygen consumption and ATP synthesis of Paramecium. Data collected indicates the incremental consumption of oxygen through irradiation with 3 J/cm(2)-100 mW or 64 J/cm(2)-1 W correlates with an increase in Paramecium ATP synthesis. The Paramecium respiration was inhibited by fluences 64 J/cm(2)-100 mW or 64 J/cm(2)-2 W and was followed by a decrease in the endogenous ATP concentration. The 1 J/cm(2)-100 mW or 1 W and 3 J/cm(2)-1 W did not affect mitochondrial activity. The results show that the fluence of 64 J/cm(2)-1 W more than the 3 J/cm(2)-100 mW causes greater efficiency in Paramecium mitochondria respiratory chain activity. Our results suggest that thanks to flat-top handpiece we used, high fluences by high-powered laser have to be reconsidered as an effective and non-invasive therapy. Possible associated benefits of deeper tissue penetration would increase treatment effectiveness and reduced irradiation time.

Note: Fully integrated active quenching circuit achieving 100 MHz count rate with custom technology single photon avalanche diodes.

PubMed

Acconcia, G; Labanca, I; Rech, I; Gulinatti, A; Ghioni, M

2017-02-01

The minimization of Single Photon Avalanche Diodes (SPADs) dead time is a key factor to speed up photon counting and timing measurements. We present a fully integrated Active Quenching Circuit (AQC) able to provide a count rate as high as 100 MHz with custom technology SPAD detectors. The AQC can also operate the new red enhanced SPAD and provide the timing information with a timing jitter Full Width at Half Maximum (FWHM) as low as 160 ps.

Collaborative Research: Atmospheric Pressure Microplasma Chemistry-Photon Synergies Final Report

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

Graves, David

Combining the effects of low temperature, atmospheric pressure microplasmas and microplasma photon sources shows greatly expanded range of applications of each of them. The plasma sources create active chemical species and these can be activated further by addition of photons and associated photochemistry. There are many ways to combine the effects of plasma chemistry and photochemistry, especially if there are multiple phases present. The project combines construction of appropriate test experimental systems, various spectroscopic diagnostics and mathematical modeling.

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

Current Advances in Lanthanide‐Doped Upconversion Nanostructures for Detection and Bioapplication

PubMed Central

Chen, Cailing

2016-01-01

Along with the development of science and technology, lanthanide‐doped upconversion nanostructures as a new type of materials have taken their place in the field of nanomaterials. Upconversion luminescence is a nonlinear optical phenomenon, which absorbs two or more photons and emits one photon. Compared with traditional luminescence materials, upconversion nanostructures have many advantages, such as weak background interference, long lifetime, low excitation energy, and strong tissue penetration. These interesting nanostructures can be applied in anticounterfeit, solar cell, detection, bioimaging, therapy, and so on. This review is focused on the current advances in lanthanide‐doped upconversion nanostructures, covering not only basic luminescence mechanism, synthesis, and modification methods but also the design and fabrication of upconversion nanostructures, like core–shell nanoparticles or nanocomposites. At last, this review emphasizes the application of upconversion nanostructure in detection and bioimaging and therapy. Learning more about the advances of upconversion nanostructures can help us better exploit their excellent performance and use them in practice. PMID:27840794

Can nanotechnology potentiate photodynamic therapy?

PubMed Central

Huang, Ying-Ying; Sharma, Sulbha K.; Dai, Tianhong; Chung, Hoon; Yaroslavsky, Anastasia; Garcia-Diaz, Maria; Chang, Julie; Chiang, Long Y.

2015-01-01

Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill cancer cells and infectious microorganisms. Due to the tendency of most photosensitizers (PS) to be poorly soluble and to form nonphotoactive aggregates, drug-delivery vehicles have become of high importance. The nanotechnology revolution has provided many examples of nanoscale drug-delivery platforms that have been applied to PDT. These include liposomes, lipoplexes, nanoemulsions, micelles, polymer nanoparticles (degradable and nondegradable), and silica nanoparticles. In some cases (fullerenes and quantum dots), the actual nanoparticle itself is the PS. Targeting ligands such as antibodies and peptides can be used to increase specificity. Gold and silver nanoparticles can provide plasmonic enhancement of PDT. Two-photon excitation or optical upconversion can be used instead of one-photon excitation to increase tissue penetration at longer wavelengths. Finally, after sections on in vivo studies and nanotoxicology, we attempt to answer the title question, “can nano-technology potentiate PDT?” PMID:26361572

Clinical advantages of carbon-ion radiotherapy

NASA Astrophysics Data System (ADS)

Tsujii, Hirohiko; Kamada, Tadashi; Baba, Masayuki; Tsuji, Hiroshi; Kato, Hirotoshi; Kato, Shingo; Yamada, Shigeru; Yasuda, Shigeo; Yanagi, Takeshi; Kato, Hiroyuki; Hara, Ryusuke; Yamamoto, Naotaka; Mizoe, Junetsu

2008-07-01

Carbon-ion radiotherapy (C-ion RT) possesses physical and biological advantages. It was started at NIRS in 1994 using the Heavy Ion Medical Accelerator in Chiba (HIMAC); since then more than 50 protocol studies have been conducted on almost 4000 patients with a variety of tumors. Clinical experiences have demonstrated that C-ion RT is effective in such regions as the head and neck, skull base, lung, liver, prostate, bone and soft tissues, and pelvic recurrence of rectal cancer, as well as for histological types including adenocarcinoma, adenoid cystic carcinoma, malignant melanoma and various types of sarcomas, against which photon therapy could be less effective. Furthermore, when compared with photon and proton RT, a significant reduction of overall treatment time and fractions has been accomplished without enhancing toxicities. Currently, the number of irradiation sessions per patient averages 13 fractions spread over approximately three weeks. This means that in a carbon therapy facility a larger number of patients than is possible with other modalities can be treated over the same period of time.

Gadolinium-Conjugated Gold Nanoshells for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

PubMed Central

Coughlin, Andrew J.; Ananta, Jeyarama S.; Deng, Nanfu; Larina, Irina V.; Decuzzi, Paolo

2014-01-01

Multimodal imaging offers the potential to improve diagnosis and enhance the specificity of photothermal cancer therapy. Toward this goal, we have engineered gadolinium-conjugated gold nanoshells and demonstrated that they enhance contrast for magnetic resonance imaging, X-Ray, optical coherence tomography, reflectance confocal microscopy, and two-photon luminescence. Additionally, these particles effectively convert near-infrared light to heat, which can be used to ablate cancer cells. Ultimately, these studies demonstrate the potential of gadolinium-nanoshells for image-guided photothermal ablation. PMID:24115690

Light in diagnosis, therapy and surgery

PubMed Central

Yun, Seok Hyun; Kwok, Sheldon J. J.

2016-01-01

Light and optical techniques have made profound impacts on modern medicine, with numerous lasers and optical devices being currently used in clinical practice to assess health and treat disease. Recent advances in biomedical optics have enabled increasingly sophisticated technologies — in particular those that integrate photonics with nanotechnology, biomaterials and genetic engineering. In this Review, we revisit the fundamentals of light–matter interactions, describe the applications of light in imaging, diagnosis, therapy and surgery, overview their clinical use, and discuss the promise of emerging light-based technologies. PMID:28649464

Characterization of the secondary neutron field produced during treatment of an anthropomorphic phantom with x-rays, protons and carbon ions

NASA Astrophysics Data System (ADS)

La Tessa, C.; Berger, T.; Kaderka, R.; Schardt, D.; Burmeister, S.; Labrenz, J.; Reitz, G.; Durante, M.

2014-04-01

Short- and long-term side effects following the treatment of cancer with radiation are strongly related to the amount of dose deposited to the healthy tissue surrounding the tumor. The characterization of the radiation field outside the planned target volume is the first step for estimating health risks, such as developing a secondary radioinduced malignancy. In ion and high-energy photon treatments, the major contribution to the dose deposited in the far-out-of-field region is given by neutrons, which are produced by nuclear interaction of the primary radiation with the beam line components and the patient’s body. Measurements of the secondary neutron field and its contribution to the absorbed dose and equivalent dose for different radiotherapy technologies are presented in this work. An anthropomorphic RANDO phantom was irradiated with a treatment plan designed for a simulated 5 × 2 × 5 cm3 cancer volume located in the center of the head. The experiment was repeated with 25 MV IMRT (intensity modulated radiation therapy) photons and charged particles (protons and carbon ions) delivered with both passive modulation and spot scanning in different facilities. The measurements were performed with active (silicon-scintillation) and passive (bubble, thermoluminescence 6LiF:Mg, Ti (TLD-600) and 7LiF:Mg, Ti (TLD-700)) detectors to investigate the production of neutral particles both inside and outside the phantom. These techniques provided the whole energy spectrum (E ⩽ 20 MeV) and corresponding absorbed dose and dose equivalent of photo neutrons produced by x-rays, the fluence of thermal neutrons for all irradiation types and the absorbed dose deposited by neutrons with 0.8 < E < 10 MeV during the treatment with scanned carbon ions. The highest yield of thermal neutrons is observed for photons and, among ions, for passively modulated beams. For the treatment with high-energy x-rays, the contribution of secondary neutrons to the dose equivalent is of the same order of magnitude as the primary radiation. In carbon therapy delivered with raster scanning, the absorbed dose deposited by neutrons in the energy region between 0.8 and 10 MeV is almost two orders of magnitude lower than charged fragments. We conclude that, within the energy range explored in this experimental work, the out-of-field dose from secondary neutrons is lowest for ions delivered by scanning, followed by passive modulation, and finally by high-energy IMRT photons.

Characterization of the secondary neutron field produced during treatment of an anthropomorphic phantom with x-rays, protons and carbon ions.

PubMed

Tessa, C La; Berger, T; Kaderka, R; Schardt, D; Burmeister, S; Labrenz, J; Reitz, G; Durante, M

2014-04-21

Short- and long-term side effects following the treatment of cancer with radiation are strongly related to the amount of dose deposited to the healthy tissue surrounding the tumor. The characterization of the radiation field outside the planned target volume is the first step for estimating health risks, such as developing a secondary radioinduced malignancy. In ion and high-energy photon treatments, the major contribution to the dose deposited in the far-out-of-field region is given by neutrons, which are produced by nuclear interaction of the primary radiation with the beam line components and the patient's body. Measurements of the secondary neutron field and its contribution to the absorbed dose and equivalent dose for different radiotherapy technologies are presented in this work. An anthropomorphic RANDO phantom was irradiated with a treatment plan designed for a simulated 5 × 2 × 5 cm³ cancer volume located in the center of the head. The experiment was repeated with 25 MV IMRT (intensity modulated radiation therapy) photons and charged particles (protons and carbon ions) delivered with both passive modulation and spot scanning in different facilities. The measurements were performed with active (silicon-scintillation) and passive (bubble, thermoluminescence ⁶LiF:Mg, Ti (TLD-600) and ⁷LiF:Mg, Ti (TLD-700)) detectors to investigate the production of neutral particles both inside and outside the phantom. These techniques provided the whole energy spectrum (E ≤ 20 MeV) and corresponding absorbed dose and dose equivalent of photo neutrons produced by x-rays, the fluence of thermal neutrons for all irradiation types and the absorbed dose deposited by neutrons with 0.8 < E < 10 MeV during the treatment with scanned carbon ions. The highest yield of thermal neutrons is observed for photons and, among ions, for passively modulated beams. For the treatment with high-energy x-rays, the contribution of secondary neutrons to the dose equivalent is of the same order of magnitude as the primary radiation. In carbon therapy delivered with raster scanning, the absorbed dose deposited by neutrons in the energy region between 0.8 and 10 MeV is almost two orders of magnitude lower than charged fragments. We conclude that, within the energy range explored in this experimental work, the out-of-field dose from secondary neutrons is lowest for ions delivered by scanning, followed by passive modulation, and finally by high-energy IMRT photons.

Monte Carlo simulation of PET and SPECT imaging of {sup 90}Y

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

Takahashi, Akihiko, E-mail: takahsr@hs.med.kyushu-u.ac.jp; Sasaki, Masayuki; Himuro, Kazuhiko

2015-04-15

Purpose: Yittrium-90 ({sup 90}Y) is traditionally thought of as a pure beta emitter, and is used in targeted radionuclide therapy, with imaging performed using bremsstrahlung single-photon emission computed tomography (SPECT). However, because {sup 90}Y also emits positrons through internal pair production with a very small branching ratio, positron emission tomography (PET) imaging is also available. Because of the insufficient image quality of {sup 90}Y bremsstrahlung SPECT, PET imaging has been suggested as an alternative. In this paper, the authors present the Monte Carlo-based simulation–reconstruction framework for {sup 90}Y to comprehensively analyze the PET and SPECT imaging techniques and to quantitativelymore » consider the disadvantages associated with them. Methods: Our PET and SPECT simulation modules were developed using Monte Carlo simulation of Electrons and Photons (MCEP), developed by Dr. S. Uehara. PET code (MCEP-PET) generates a sinogram, and reconstructs the tomography image using a time-of-flight ordered subset expectation maximization (TOF-OSEM) algorithm with attenuation compensation. To evaluate MCEP-PET, simulated results of {sup 18}F PET imaging were compared with the experimental results. The results confirmed that MCEP-PET can simulate the experimental results very well. The SPECT code (MCEP-SPECT) models the collimator and NaI detector system, and generates the projection images and projection data. To save the computational time, the authors adopt the prerecorded {sup 90}Y bremsstrahlung photon data calculated by MCEP. The projection data are also reconstructed using the OSEM algorithm. The authors simulated PET and SPECT images of a water phantom containing six hot spheres filled with different concentrations of {sup 90}Y without background activity. The amount of activity was 163 MBq, with an acquisition time of 40 min. Results: The simulated {sup 90}Y-PET image accurately simulated the experimental results. PET image is visually superior to SPECT image because of the low background noise. The simulation reveals that the detected photon number in SPECT is comparable to that of PET, but the large fraction (approximately 75%) of scattered and penetration photons contaminates SPECT image. The lower limit of {sup 90}Y detection in SPECT image was approximately 200 kBq/ml, while that in PET image was approximately 100 kBq/ml. Conclusions: By comparing the background noise level and the image concentration profile of both the techniques, PET image quality was determined to be superior to that of bremsstrahlung SPECT. The developed simulation codes will be very useful in the future investigations of PET and bremsstrahlung SPECT imaging of {sup 90}Y.« less

Pre-Conditioning with Low-Level Laser (Light) Therapy: Light Before the Storm

PubMed Central

Agrawal, Tanupriya; Gupta, Gaurav K.; Rai, Vikrant; Carroll, James D.; Hamblin, Michael R.

2014-01-01

Pre-conditioning by ischemia, hyperthermia, hypothermia, hyperbaric oxygen (and numerous other modalities) is a rapidly growing area of investigation that is used in pathological conditions where tissue damage may be expected. The damage caused by surgery, heart attack, or stroke can be mitigated by pre-treating the local or distant tissue with low levels of a stress-inducing stimulus, that can induce a protective response against subsequent major damage. Low-level laser (light) therapy (LLLT) has been used for nearly 50 years to enhance tissue healing and to relieve pain, inflammation and swelling. The photons are absorbed in cytochrome(c) oxidase (unit four in the mitochondrial respiratory chain), and this enzyme activation increases electron transport, respiration, oxygen consumption and ATP production. A complex signaling cascade is initiated leading to activation of transcription factors and up- and down-regulation of numerous genes. Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance. PMID:25552961

Neutron therapy of resistant thyroid gland cancer

NASA Astrophysics Data System (ADS)

Choynzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Lisin, V. A.; Novikov, V. A.; Musabaeva, L. I.

2017-09-01

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons c. The study included 45 patients with thyroid gland cancers who received the combined modality treatment and radiation therapy alone with the use of 6.3 MeV fast neutrons generated within U-120 cyclotron. The clinical trial of neutron-photon therapy used alone and in combination with the surgery for the patients with aggressive forms of thyroid cancer showed feasibility of increasing the effectiveness of treatment due to the reduction in the incidence of local recurrences. In addition, satisfactory treatment tolerance and absence of severe specific complications dictate the necessity of prospective studies to improve treatment outcomes.

Photonic Network R&D Activities in Japan-Current Activities and Future Perspectives

NASA Astrophysics Data System (ADS)

Kitayama, Ken-Ichi; Miki, Tetsuya; Morioka, Toshio; Tsushima, Hideaki; Koga, Masafumi; Mori, Kazuyuki; Araki, Soichiro; Sato, Ken-Ichi; Onaka, Hiroshi; Namiki, Shu; Aoyama, Tomonori

2005-10-01

R&D activities on photonic networks in Japan are presented. First, milestones in current ongoing R&D programs supported by Japanese government agencies are introduced, including long-distance and wavelength division multiplexing (WDM) fiber transmission, wavelength routing, optical burst switching (OBS), and control-plane technology for IP backbone networks. Their goal was set to evolve a legacy telecommunications network to IP-over-WDM networks by introducing technologies for WDM and wavelength routing. We then discuss the perspectives of so-called PHASE II R&D programs for photonic networks over the next 5 years until 2010, by focusing on the report that has been recently issued by the Photonic Internet Forum (PIF), a consortium that has major carriers, telecom vendors, and Japanese academics as members. The PHASE II R&D programs should serve to establish a photonic platform to provide abundant bandwidth on demand, at any time on a real-time basis, through the customer's initiative to promote bandwidth-rich applications, such as grid computing, real-time digital-cinema streaming, medical and educational applications, and network storage in e-commerce.

Smart photonic materials for theranostic applications

NASA Astrophysics Data System (ADS)

Keum, Do Hee; Beack, Songeun; Hahn, Sei Kwang

2017-05-01

We developed melanoidin nanoparticles for in vivo noninvasive photoacoustic mapping of sentinel lymph nodes, photoacoustic tomography of gastro-intestinal tracts, and photothermal ablation cancer therapy. In addition, we developed cell-integrated poly(ethylene glycol) hydrogels for in vivo optogenetic sensing and therapy. Real-time optical readout of encapsulated heat-shock-protein-coupled fluorescent reporter cells made it possible to measure the nanotoxicity of cadmium-based quantum dots in vivo. Using optogenetic cells producing glucagon-like peptide-1, we performed lightcontrolled diabetic therapy for glucose homeostasis. Finally, we developed a smart contact lens composed of biosensors, drug delivery systems, and power sources for the treatment of diabetes as a model disease.

Relation between lineal energy distribution and relative biological effectiveness for photon beams according to the microdosimetric kinetic model.

PubMed

Okamoto, Hiroyuki; Kanai, Tatsuaki; Kase, Yuki; Matsumoto, Yoshitaka; Furusawa, Yoshiya; Fujita, Yukio; Saitoh, Hidetoshi; Itami, Jun; Kohno, Toshiyuki

2011-01-01

Our cell survival data showed the obvious dependence of RBE on photon energy: The RBE value for 200 kV X-rays was approximately 10% greater than those for mega-voltage photon beams. In radiation therapy using mega-voltage photon beams, the photon energy distribution outside the field is different with that in the radiation field because of a large number of low energy scattering photons. Hence, the RBE values outside the field become greater. To evaluate the increase in RBE, the method of deriving the RBE using the Microdosimetric Kinetic model (MK model) was proposed in this study. The MK model has two kinds of the parameters, tissue-specific parameters and the dose-mean lineal energy derived from the lineal energy distributions measured with a Tissue-Equivalent Proportional Counter (TEPC). The lineal energy distributions with the same geometries of the cell irradiations for 200 kV X-rays, (60)Co γ-rays, and 6 MV X-rays were obtained with the TEPC and Monte Carlo code GEANT4. The measured lineal energy distribution for 200 kV X-rays was quite different from those for mega-voltage photon beams. The dose-mean lineal energy of 200 kV X-rays showed the greatest value, 4.51 keV/µm, comparing with 2.34 and 2.36 keV/µm for (60)Co γ-rays and 6 MV X-rays, respectively. By using the results of the TEPC and cell irradiations, the tissue-specific parameters in the MK model were determined. As a result, the RBE of the photon beams (y(D): 2~5 keV/µm) in arbitrary conditions can be derived by the measurements only or the calculations only of the dose-mean lineal energy.

Multichannel Dosimeter and α-Al2O3:C Optically Stimulated Luminescence (OSL) Fiber Sensors for Use in Radiation Therapy—Evaluation With Photon Beams

NASA Astrophysics Data System (ADS)

Magne, Sylvian; de Carlan, Loïc; Bordy, Jean-Marc; Isambert, Aurélie; Bridier, André; Ferdinand, Pierre

2011-04-01

A multichannel OSL fiber optic dosimeter based on optically stimulated luminescence (OSL) of alumina is proposed for online in vivo dosimetry (IVD) in radiation therapy (RT). Two types of dosimetric-grade Al2O3:C crystals are compared and show different behavior according to manufacturing process. Metrological validations have been performed with a Saturne 43 LINAC in reference conditions at CEA LIST LNHB (French Ionizing Radiation Reference Laboratory). The dose response of OSL integrals under photon beam irradiation (6, 12, and 20 MV) show sublinearity behavior modeled by second-order equations and exhibit a small energy dependence (between 0.7% and 1.4%), explained by a modified intermediate cavity model adapted to a LINAC photon spectrum. Preclinical tests at Institut Gustave Roussy (IGR) prove that a proper design for a PMMA build-up cap leads to a low dependence vs photon beam orientation (± 1.5% and ± 0.9%) and vs field size in view of surface measurements.

Factors affecting ultraviolet-A photon emission from β-irradiated human keratinocyte cells.

PubMed

Le, M; Mothersill, C E; Seymour, C B; Ahmad, S B; Armstrong, A; Rainbow, A J; McNeill, F E

2015-08-21

The luminescence intensity of 340±5 nm photons emitted from HaCaT (human keratinocyte) cells was investigated using a single-photon-counting system during cellular exposure to (90)Y β-particles. Multiple factors were assessed to determine their influence upon the quantity and pattern of photon emission from β-irradiated cells. Exposure of 1 x 10(4) cells/5 mL to 703 μCi resulted in maximum UVA photoemission at 44.8 x 10(3)±2.5 x 10(3) counts per second (cps) from live HaCaT cells (background: 1-5 cps); a 16-fold increase above cell-free controls. Significant biophoton emission was achieved only upon stimulation and was also dependent upon presence of cells. UVA luminescence was measured for (90)Y activities 14 to 703 μCi where a positive relationship between photoemission and (90)Y activity was observed. Irradiation of live HaCaT cells plated at various densities produced a distinct pattern of emission whereby luminescence increased up to a maximum at 1 x 10(4) cells/5 mL and thereafter decreased. However, this result was not observed in the dead cell population. Both live and dead HaCaT cells were irradiated and were found to demonstrate different rates of photon emission at low β activities (⩽400 μCi). Dead cells exhibited greater photon emission rates than live cells which may be attributable to metabolic processes taking place to modulate the photoemissive effect. The results indicate that photon emission from HaCaT cells is perturbed by external stimulation, is dependent upon the activity of radiation delivered, the density of irradiated cells, and cell viability. It is postulated that biophoton emission may be modulated by a biological or metabolic process.

Oxygen dependence of two-photon activation of zinc and copper phthalocyanine tetrasulfonate in Jurkat cells.

PubMed

Mir, Youssef; van Lier, Johan E; Paquette, Benoit; Houde, Daniel

2008-01-01

Photodynamic therapy (PDT), the use of light-activated drugs, is a promising treatment of cancer as well as several nonmalignant conditions. However, the efficacy of one-photon (1-gamma) PDT is limited by hypoxia, which can prevent the production of the cytotoxic singlet oxygen ((1)O(2)) species, leading to tumor resistance to PDT. To solve this problem, we propose an irradiation protocol based on a simultaneous, two-photon (2-gamma) excitation of the photosensitizer (Ps). Excitation of the Ps triplet state leads to an upper excited triplet state T(n) with distinct photochemical properties, which could inflict biologic damage independent of the presence of molecular oxygen. To determine the potential of a 2-gamma excitation process, Jurkat cells were incubated with zinc or copper phthalocyanine tetrasulfonate (ZnPcS(4) or CuPcS(4)). ZnPcS(4) is a potent (1)O(2) generator in 1-gamma PDT, while CuPcS(4) is inactive under these conditions. Jurkat cells incubated with either ZnPcS(4) or CuPcS(4) were exposed to a 670 nm continuous laser (1-gamma PDT), 532 nm pulsed-laser light (2-gamma PDT), or a combination of 532 and 670 nm (2-gamma PDT). The efficacy of ZnPcS(4) to photoinactivate the Jurkat cells decreased as the concentration of oxygen decreased for both the 1-gamma and 2-gamma protocols. In the case of CuPcS(4), cell phototoxicity was measured only following 2-gamma irradiation, and its efficacy also decreased at a lower oxygen concentration. Our results suggest that for CuPcS(4) the T(n) excited state can be populated after 2-gamma irradiation at 532 nm or the combination of 532 and 670 nm light. Dependency of phototoxicity upon aerobic conditions for both 1-gamma and 2-gamma PDT suggests that reactive oxygen species play an important role in 1-gamma and 2-gamma PDT.

SU-E-T-128: Dosimetric Characteristics of Gafchromic EBT3 Films for Megavoltage Photon and Proton Beams.

PubMed

Hayashi, N; Kato, H; Yada, R; Matsunaga, T; Ehara, I; Adachi, Y

2012-06-01

Gafchromic film for quantitative analysis was renewed from EBT2 to EBT3 film in November 2011. The purpose of this study is to investigate the relevant characteristics of EBT3 film for its application in dosimetric verification for IMRT/VMAT or proton therapy. We investigated the characteristics of EBT3 film with comparison of previous EBT2 film. The experiments in this study composed two categories. At first, the photo spectroscopy for the irradiated film was compared between EBT2 and EBT3. The film 1 day after the irradiation was analyzed by a photo spectrometer (SR520: JASCO Corporation, Japan). Secondly, we investigated several calibration curves which obtained by same batch. The films were calibrated by irradiation the films to 13 dose steps. The irradiated films were scanned by a flatbed scanner (ES-10000XL, Epson-Seiko Corporation, Japan). The difference on scan orientation was evaluated alternate portrait and landscape directions. The photon and proton beams were delivered from Clinac 21EX (Varian) and Mitsubishi machine, respectively. The peak absorption wavelength of EBT3 film and its response at all active range were basically same with that of EBT2 film. The peak wavelength of photo absorption in EBT3 was observed at 585 and 634 nm. The fog optical density was increased due to the hazy matte polyester for active layer. However, there is no change the tendency of the calibration curve responding to megavoltage photon and proton beams. The scan orientation dependency of EBT3 film was observed with similar to EBT2 film. The optical density of portrait orientation was 10% higher than that of landscape orientation. The dosimetric characteristics of EBT3 film were basically same with EBT2 film. With regard to the matte polyester, the creation of Newton's rings during scanning procedure was reduced. However, the suitable scan protocol should be used for accurate film dosimetry. © 2012 American Association of Physicists in Medicine.

Design Study of the Absorber Detector of a Compton Camera for On-Line Control in Ion Beam Therapy

NASA Astrophysics Data System (ADS)

Richard, M.-H.; Dahoumane, M.; Dauvergne, D.; De Rydt, M.; Dedes, G.; Freud, N.; Krimmer, J.; Letang, J. M.; Lojacono, X.; Maxim, V.; Montarou, G.; Ray, C.; Roellinghoff, F.; Testa, E.; Walenta, A. H.

2012-10-01

The goal of this study is to tune the design of the absorber detector of a Compton camera for prompt γ-ray imaging during ion beam therapy. The response of the Compton camera to a photon point source with a realistic energy spectrum (corresponding to the prompt γ-ray spectrum emitted during the carbon irradiation of a water phantom) is studied by means of Geant4 simulations. Our Compton camera consists of a stack of 2 mm thick silicon strip detectors as a scatter detector and of a scintillator plate as an absorber detector. Four scintillators are considered: LYSO, NaI, LaBr3 and BGO. LYSO and BGO appear as the most suitable materials, due to their high photo-electric cross-sections, which leads to a high percentage of fully absorbed photons. Depth-of-interaction measurements are shown to have limited influence on the spatial resolution of the camera. In our case, the thickness which gives the best compromise between a high percentage of photons that are fully absorbed and a low parallax error is about 4 cm for the LYSO detector and 4.5 cm for the BGO detector. The influence of the width of the absorber detector on the spatial resolution is not very pronounced as long as it is lower than 30 cm.

SU-F-T-684: Analysis of Cherenkov Excitation in Tissue and the Feasibility of Cherenkov Excited Photodynamic Therapy

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

Saunders, Sara L; Andreozzi, Jacqueline M; Pogue, Brian W

Purpose: The irradiation of photodynamic agents with radiotherapy beams has been demonstrated to enhance tumor killing in various studies, and one proposed mechanism is the optical fluence of Cherenkov emission activating the photosensitizer. This mechanism is explored in Monte Carlo simulations of fluence as well as laboratory measurements of fluence and radical oxygen species. Methods: Simulations were completed using GAMOS/GEANT4 with a 6 MV photon beam in tissue. The effects of blood vessel diameter, blood oxygen saturation, and beam size were examined, recording spectral fluence. Experiments were carried out in solutions of photosensitizer and phantoms. Results: Cherenkov produced by amore » 100×100um{sup 2} 6 MV beam resulted in fluence of less than 1 nJ/cm{sup 2}/Gy per 1 nm wavelength. At this microscopic level, differences in absorption of blood and water in the tissue affected the fluence spectrum, but variation in blood oxygenation had little effect. Light in tissue resulting from larger (10mm ×10mm) 6 MV beams had greater fluence due to light transport and elastic scattering of optical photons, but this transport process also resulted in higher absorption shifts. Therefore, the spectrum produced by a microscopic beam was weighted more heavily in UV/blue wavelengths than the spectrum at the macroscopic level. At the macroscopic level, the total fluence available for absorption by Verteporfin (BPD) in tissue approached uJ/cm{sup 2} for a high radiation dose, indicating that photodynamic activation seems unlikely. Tissue phantom confirmation of these light levels supported this observation, and photosensitization measurements with a radical oxygen species reporter are ongoing. Conclusion: Simulations demonstrated that fluence produced by Cherenkov in tissue by 6 MV photon beams at typical radiotherapy doses appears insufficient to activate photosensitizers to the level required for threshold effects, yet this disagrees with published biological experiments. Experimental validation in tissue phantoms and cell studies are ongoing to clarify this discrepancy. Funding from NIH grant R01CA109558.« less

Photonics applications and web engineering: WILGA Summer 2016

NASA Astrophysics Data System (ADS)

Romaniuk, Ryszard S.

2016-09-01

Wilga Summer 2016 Symposium on Photonics Applications and Web Engineering was held on 29 May - 06 June. The Symposium gathered over 350 participants, mainly young researchers active in optics, optoelectronics, photonics, electronics technologies and applications. There were presented around 300 presentations in a few main topical tracks including: bio-photonics, optical sensory networks, photonics-electronics-mechatronics co-design and integration, large functional system design and maintenance, Internet of Thins, and other. The paper is an introduction the 2016 WILGA Summer Symposium Proceedings, and digests some of the Symposium chosen key presentations.

Photonics applications and web engineering: WILGA Summer 2015

NASA Astrophysics Data System (ADS)

Romaniuk, Ryszard S.

2015-09-01

Wilga Summer 2015 Symposium on Photonics Applications and Web Engineering was held on 23-31 May. The Symposium gathered over 350 participants, mainly young researchers active in optics, optoelectronics, photonics, electronics technologies and applications. There were presented around 300 presentations in a few main topical tracks including: bio-photonics, optical sensory networks, photonics-electronics-mechatronics co-design and integration, large functional system design and maintenance, Internet of Thins, and other. The paper is an introduction the 2015 WILGA Summer Symposium Proceedings, and digests some of the Symposium chosen key presentations.

Poly β-cyclodextrin/TPdye nanomicelle-based two-photon nanoprobe for caspase-3 activation imaging in live cells and tissues.

PubMed

Yan, Huijuan; He, Leiliang; Zhao, Wenjie; Li, Jishan; Xiao, Yue; Yang, Ronghua; Tan, Weihong

2014-11-18

Two-photon excitation (TPE) with near-infrared (NIR) photons as the excitation source has important advantages over conventional one-photon excitation (OPE) in the field of biomedical imaging. β-cyclodextrin polymer (βCDP)-based two-photon absorption (TPA) fluorescent nanomicelle exhibits desirable two-photon-sensitized fluorescence properties, high photostability, high cell-permeability and excellent biocompatibility. By combination of the nanostructured two-photon dye (TPdye)/βCDP nanomicelle with the TPE technique, herein we have designed a TPdye/βCDP nanomicelle-based TPA fluorescent nanoconjugate for enzymatic activity assay in biological fluids, live cells and tissues. This sensing system is composed of a trans-4-[p-(N,N-diethylamino)styryl]-N-methylpyridinium iodide (DEASPI)/βCDP nanomicelle as TPA fluorophore and carrier vehicle for delivery of a specific peptide sequence to live cell through fast endocytosis, and an adamantine (Ad)-GRRRDEVDK-BHQ2 (black hole quencher 2) peptide (denoted as Ad-DEVD-BHQ2) anchored on the DEASPI/βCDP nanomicelle's surface to form TPA DEASPI/βCDP@Ad-DEVD-BHQ2 nanoconjugate by the βCD/Ad host-guest inclusion strategy. Successful in vitro and in vivo enzymatic activities assay of caspase-3 was demonstrated with this sensing strategy. Our results reveal that this DEASPI/βCDP@Ad-DEVD-BHQ2 nanoconjugate not only is a robust, sensitive and selective sensor for quantitative assay of caspase-3 in the complex biological environment but also can be efficiently delivered into live cells as well as tissues and act as a "signal-on" fluorescent biosensor for specific, high-contrast imaging of enzymatic activities. This DEASPI/βCDP@Ad-DEVD-BHQ2 nanoconjugate provides a new opportunity to screen enzyme inhibitors and evaluate the apoptosis-associated disease progression. Moreover, our design also provides a methodology model scheme for development of future TPdye/βCDP nanomicelle-based two-photon fluorescent probes for in vitro or in vivo determination of biological or biologically relevant species.

First demonstration of gold nanorods-mediated photodynamic therapeutic destruction of tumors via near infra-red light activation.

PubMed

Vankayala, Raviraj; Huang, Yu-Kuan; Kalluru, Poliraju; Chiang, Chi-Shiun; Hwang, Kuo Chu

2014-04-24

Previously, a large volume of papers reports that gold nanorods (Au NRs) are able to effectively kill cancer cells upon high laser doses (usually 808 nm, 1-48 W/cm²) irradiation, leading to hyperthermia-induced destruction of cancer cells, i.e, photothermal therapy (PTT) effects. Combination of Au NRs-mediated PTT and organic photosensitizers-mediated photodynamic therapy (PDT) were also reported to achieve synergistic PTT and PDT effects on killing cancer cells. Herein, we demonstrate for the first time that Au NRs alone can sensitize formation of singlet oxygen (¹O₂) and exert dramatic PDT effects on complete destrcution of tumors in mice under very low LED/laser doses of single photon NIR (915 nm, <130 mW/cm²) light excitation. By changing the NIR light excitation wavelengths, Au NRs-mediated phototherapeutic effects can be switched from PDT to PTT or combination of both. Both PDT and PTT effects were confirmed by measurements of reactive oxygen species (ROS) and heat shock protein (HSP 70), singlet oxygen sensor green (SOSG) sensing, and sodium azide quenching in cellular experiments. In vivo mice experiments further show that the PDT effect via irradiation of Au NRs by 915 nm can destruct the B16F0 melanoma tumor in mice far more effectively than doxorubicin (a clinically used anti-cancer drug) as well as the PTT effect (via irradiation of Au NRs by 780 nm light). In addition, we show that Au NRs can emit single photon-induced fluorescence to illustrate their in vivo locations/distribution. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Silicon-graphene photonic devices

NASA Astrophysics Data System (ADS)

Yin, Yanlong; Li, Jiang; Xu, Yang; Tsang, Hon Ki; Dai, Daoxin

2018-06-01

Silicon photonics has attracted much attention because of the advantages of CMOS (complementary-metal-oxide-semiconductor) compatibility, ultra-high integrated density, etc. Great progress has been achieved in the past decades. However, it is still not easy to realize active silicon photonic devices and circuits by utilizing the material system of pure silicon due to the limitation of the intrinsic properties of silicon. Graphene has been regarded as a promising material for optoelectronics due to its unique properties and thus provides a potential option for realizing active photonic integrated devices on silicon. In this paper, we present a review on recent progress of some silicon-graphene photonic devices for photodetection, all-optical modulation, as well as thermal-tuning. Project supported by the National Major Research and Development Program (No. 2016YFB0402502), the National Natural Science Foundation of China (Nos. 11374263, 61422510, 61431166001, 61474099, 61674127), and the National Key Research and Development Program (No. 2016YFA0200200).

Optics Communications: Special issue on Polymer Photonics and Its Applications

NASA Astrophysics Data System (ADS)

Zhang, Ziyang; Pitwon, Richard C. A.; Feng, Jing

2016-03-01

In the last decade polymer photonics has witnessed a tremendous boost in research efforts and practical applications. Polymer materials can be engineered to exhibit unique optical and electrical properties. Extremely transparent and reliable passive optical polymers have been made commercially available and paved the ground for the development of various waveguide components. Advancement in the research activities regarding the synthesis of active polymers has enabled devices such as ultra-fast electro-optic modulators, efficient white light emitting diodes, broadband solar cells, flexible displays, and so on. The fabrication technology is not only fast and cost-effective, but also provides flexibility and broad compatibility with other semiconductor processing technologies. Reports show that polymers have been integrated in photonic platforms such as silicon-on-insulator (SOI), III-V semiconductors, and silica PLCs, and vice versa, photonic components made from a multitude of materials have been integrated, in a heterogeneous/hybrid manner, in polymer photonic platforms.

Electrically pumped edge-emitting photonic bandgap semiconductor laser

DOEpatents

Lin, Shawn-Yu; Zubrzycki, Walter J.

2004-01-06

A highly efficient, electrically pumped edge-emitting semiconductor laser based on a one- or two-dimensional photonic bandgap (PBG) structure is described. The laser optical cavity is formed using a pair of PBG mirrors operating in the photonic band gap regime. Transverse confinement is achieved by surrounding an active semiconductor layer of high refractive index with lower-index cladding layers. The cladding layers can be electrically insulating in the passive PBG mirror and waveguide regions with a small conducting aperture for efficient channeling of the injection pump current into the active region. The active layer can comprise a quantum well structure. The quantum well structure can be relaxed in the passive regions to provide efficient extraction of laser light from the active region.

Monitor unit calculations for external photon and electron beams: Report of the AAPM Therapy Physics Committee Task Group No. 71

PubMed Central

Gibbons, John P.; Antolak, John A.; Followill, David S.; Huq, M. Saiful; Klein, Eric E.; Lam, Kwok L.; Palta, Jatinder R.; Roback, Donald M.; Reid, Mark; Khan, Faiz M.

2014-01-01

A protocol is presented for the calculation of monitor units (MU) for photon and electron beams, delivered with and without beam modifiers, for constant source-surface distance (SSD) and source-axis distance (SAD) setups. This protocol was written by Task Group 71 of the Therapy Physics Committee of the American Association of Physicists in Medicine (AAPM) and has been formally approved by the AAPM for clinical use. The protocol defines the nomenclature for the dosimetric quantities used in these calculations, along with instructions for their determination and measurement. Calculations are made using the dose per MU under normalization conditions, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$D_0^\\prime $\\end{document}D0′, that is determined for each user's photon and electron beams. For electron beams, the depth of normalization is taken to be the depth of maximum dose along the central axis for the same field incident on a water phantom at the same SSD, where \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$D_0^\\prime $\\end{document}D0′ = 1 cGy/MU. For photon beams, this task group recommends that a normalization depth of 10 cm be selected, where an energy-dependent \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$D_0^\\prime $\\end{document}D0′ ≤ 1 cGy/MU is required. This recommendation differs from the more common approach of a normalization depth of dm, with \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$D_0^\\prime $\\end{document}D0′ = 1 cGy/MU, although both systems are acceptable within the current protocol. For photon beams, the formalism includes the use of blocked fields, physical or dynamic wedges, and (static) multileaf collimation. No formalism is provided for intensity modulated radiation therapy calculations, although some general considerations and a review of current calculation techniques are included. For electron beams, the formalism provides for calculations at the standard and extended SSDs using either an effective SSD or an air-gap correction factor. Example tables and problems are included to illustrate the basic concepts within the presented formalism. PMID:24593704

Flexible integration of free-standing nanowires into silicon photonics.

PubMed

Chen, Bigeng; Wu, Hao; Xin, Chenguang; Dai, Daoxin; Tong, Limin

2017-06-14

Silicon photonics has been developed successfully with a top-down fabrication technique to enable large-scale photonic integrated circuits with high reproducibility, but is limited intrinsically by the material capability for active or nonlinear applications. On the other hand, free-standing nanowires synthesized via a bottom-up growth present great material diversity and structural uniformity, but precisely assembling free-standing nanowires for on-demand photonic functionality remains a great challenge. Here we report hybrid integration of free-standing nanowires into silicon photonics with high flexibility by coupling free-standing nanowires onto target silicon waveguides that are simultaneously used for precise positioning. Coupling efficiency between a free-standing nanowire and a silicon waveguide is up to ~97% in the telecommunication band. A hybrid nonlinear-free-standing nanowires-silicon waveguides Mach-Zehnder interferometer and a racetrack resonator for significantly enhanced optical modulation are experimentally demonstrated, as well as hybrid active-free-standing nanowires-silicon waveguides circuits for light generation. These results suggest an alternative approach to flexible multifunctional on-chip nanophotonic devices.Precisely assembling free-standing nanowires for on-demand photonic functionality remains a challenge. Here, Chen et al. integrate free-standing nanowires into silicon waveguides and show all-optical modulation and light generation on silicon photonic chips.

Constituent components of out-of-field scatter dose for 18-MV intensity modulated radiation therapy versus 3-dimensional conformal radiation therapy: a comparison with 6-MV and implications for carcinogenesis.

PubMed

Ruben, Jeremy D; Smith, Ryan; Lancaster, Craig M; Haynes, Matthew; Jones, Phillip; Panettieri, Vanessa

2014-11-01

To characterize and compare the components of out-of-field dose for 18-MV intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) and their 6-MV counterparts and consider implications for second cancer induction. Comparable plans for each technique/energy were delivered to a water phantom with a sloping wall; under full scatter conditions; with field edge abutting but outside the bath to prevent internal/phantom scatter; and with shielding below the linear accelerator head to attenuate head leakage. Neutron measurements were obtained from published studies. Eighteen-megavolt IMRT produces 1.7 times more out-of-field scatter than 18-MV 3D-CRT. In absolute terms, however, differences are just approximately 0.1% of central axis dose. Eighteen-megavolt IMRT reduces internal/patient scatter by 13%, but collimator scatter (C) is 2.6 times greater than 18-MV 3D-CRT. Head leakage (L) is minimal. Increased out-of-field photon scatter from 18-MV IMRT carries out-of-field second cancer risks of approximately 0.2% over and above the 0.4% from 18-MV 3D-CRT. Greater photoneutron dose from 18-MV IMRT may result in further maximal, absolute increased risk to peripheral tissue of approximately 1.2% over 18-MV 3D-CRT. Out-of-field photon scatter remains comparable for the same modality irrespective of beam energy. Machine scatter (C+L) from 18 versus 6 MV is 1.2 times higher for IMRT and 1.8 times for 3D-CRT. It is 4 times higher for 6-MV IMRT versus 3D-CRT. Reduction in internal scatter with 18 MV versus 6 MV is 27% for 3D-CRT and 29% for IMRT. Compared with 6-MV 3D-CRT, 18-MV IMRT increases out-of-field second cancer risk by 0.2% from photons and adds 0.28-2.2% from neutrons. Out-of-field photon dose seems to be independent of beam energy for both techniques. Eighteen-megavolt IMRT increases out-of-field scatter 1.7-fold over 3D-CRT because of greater collimator scatter despite reducing internal/patient scatter. Out-of-field carcinogenic risk is thus increased (but improved in-field dose conformity may offset this). Potentially increased carcinogenic risk should be weighed against any benefit 18-MV IMRT may provide. Copyright © 2014 Elsevier Inc. All rights reserved.

Constituent Components of Out-of-Field Scatter Dose for 18-MV Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy: A Comparison With 6-MV and Implications for Carcinogenesis

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

Ruben, Jeremy D., E-mail: jeremy.ruben@wbrc.org.au; Department of Surgery, Monash University, Melbourne; Smith, Ryan

Purpose: To characterize and compare the components of out-of-field dose for 18-MV intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) and their 6-MV counterparts and consider implications for second cancer induction. Methods and Materials: Comparable plans for each technique/energy were delivered to a water phantom with a sloping wall; under full scatter conditions; with field edge abutting but outside the bath to prevent internal/phantom scatter; and with shielding below the linear accelerator head to attenuate head leakage. Neutron measurements were obtained from published studies. Results: Eighteen-megavolt IMRT produces 1.7 times more out-of-field scatter than 18-MV 3D-CRT. Inmore » absolute terms, however, differences are just approximately 0.1% of central axis dose. Eighteen-megavolt IMRT reduces internal/patient scatter by 13%, but collimator scatter (C) is 2.6 times greater than 18-MV 3D-CRT. Head leakage (L) is minimal. Increased out-of-field photon scatter from 18-MV IMRT carries out-of-field second cancer risks of approximately 0.2% over and above the 0.4% from 18-MV 3D-CRT. Greater photoneutron dose from 18-MV IMRT may result in further maximal, absolute increased risk to peripheral tissue of approximately 1.2% over 18-MV 3D-CRT. Out-of-field photon scatter remains comparable for the same modality irrespective of beam energy. Machine scatter (C+L) from 18 versus 6 MV is 1.2 times higher for IMRT and 1.8 times for 3D-CRT. It is 4 times higher for 6-MV IMRT versus 3D-CRT. Reduction in internal scatter with 18 MV versus 6 MV is 27% for 3D-CRT and 29% for IMRT. Compared with 6-MV 3D-CRT, 18-MV IMRT increases out-of-field second cancer risk by 0.2% from photons and adds 0.28-2.2% from neutrons. Conclusions: Out-of-field photon dose seems to be independent of beam energy for both techniques. Eighteen-megavolt IMRT increases out-of-field scatter 1.7-fold over 3D-CRT because of greater collimator scatter despite reducing internal/patient scatter. Out-of-field carcinogenic risk is thus increased (but improved in-field dose conformity may offset this). Potentially increased carcinogenic risk should be weighed against any benefit 18-MV IMRT may provide.« less

In vivo demonstration of enhanced radiotherapy using rare earth doped titania nanoparticles†

PubMed Central

Townley, Helen E.; Kim, Jeewon; Dobson, Peter J.

2017-01-01

Radiation therapy is often limited by damage to healthy tissue and associated side-effects; restricting radiation to ineffective doses. Preferential incorporation of materials into tumour tissue can enhance the effect of radiation. Titania has precedent for use in photodynamic therapy (PDT), generating reactive oxygen species (ROS) upon photoexcitation, but is limited by the penetration depth of UV light. Optimization of a nanomaterial for interaction with X-rays could be used for deep tumour treatment. As such, titania nanoparticles were doped with gadolinium to optimize the localized energy absorption from a conventional medical X-ray, and further optimized by the addition of other rare earth (RE) elements. These elements were selected due to their large X-ray photon interaction cross-section, and potential for integration into the titania crystal structure. Specific activation of the nanoparticles by X-ray can result in generation of ROS leading to cell death in a tumour-localized manner. We show here that intratumoural injection of RE doped titania nanoparticles can enhance the efficacy of radiotherapy in vivo. PMID:22767269

EUD-based biological optimization for carbon ion therapy

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

Brüningk, Sarah C., E-mail: sarah.brueningk@icr.ac.uk; Kamp, Florian; Wilkens, Jan J.

2015-11-15

Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalentmore » uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon therapy, the optimization by biological objective functions resulted in slightly superior treatment plans in terms of final EUD for the organs at risk (OARs) compared to voxel-based optimization approaches. This observation was made independent of the underlying objective function metric. An absolute gain in OAR sparing was observed for quadratic objective functions, whereas intersecting DVHs were found for logistic approaches. Even for considerable under- or overestimations of the used effect- or dose–volume parameters during the optimization, treatment plans were obtained that were of similar quality as the results of a voxel-based optimization. Conclusions: EUD-based optimization with either of the presented concepts can successfully be applied to treatment plan optimization. This makes EUE-based optimization for carbon ion therapy a useful tool to optimize more specifically in the sense of biological outcome while voxel-to-voxel variations of the biological effectiveness are still properly accounted for. This may be advantageous in terms of computational cost during treatment plan optimization but also enables a straight forward comparison of different fractionation schemes or treatment modalities.« less

Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer.

PubMed

Wo, Jennifer Y; Mamon, Harvey J; Ferrone, Cristina R; Ryan, David P; Blaszkowsky, Lawrence S; Kwak, Eunice L; Tseng, Yolanda D; Napolitano, Brian N; Ancukiewicz, Marek; Swanson, Richard S; Lillemoe, Keith D; Fernandez-del Castillo, Carlos; Hong, Theodore S

2014-01-01

In this phase I study, we sought to determine the feasibility and tolerability of neoadjuvant short course radiotherapy (SC-CRT) delivered with photon RT with concurrent capecitabine for resectable pancreatic adenocarcinoma. Ten patients with localized, resectable pancreatic adenocarcinoma were enrolled from December 2009 to August 2011. In dose level I, patients received 3 Gy × 10. In dose level 2, patients received 5 Gy × 5 (every other day). In dose level 3, patients received 5 Gy × 5 (consecutive days). Capecitabine was given during weeks 1 and 2. Surgery was performed 1-3 weeks after completion of chemotherapy. With an intended accrual of 12 patients, the study was closed early due to unexpected intraoperative complications. Compared to the companion phase I proton study, patients treated with photons had increased intraoperative RT fibrosis reported by surgeons (27% vs. 63%). Among those undergoing a Whipple resection, increased RT fibrosis translated to an increased mean OR time of 69 min. Dosimetric comparison revealed significantly increased low dose exposure to organs at risk for patients treated with photon RT. This phase I experience evaluating the tolerability of neoadjuvant SC-CRT with photon RT closed early due to unexpected intraoperative complications. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Flexible Guidance of Ultra-Short Laser Pulses in Ophthalmic Therapy Systems].

PubMed

Blum, J; Blum, M; Rill, M S; Haueisen, J

2017-01-01

In the last 20 years, the role of ultrashort pulsed lasers in ophthalmology has become increasingly important. However, it is still impossible to guide ultra-short laser pulses with standard glass fibres. The highly energetic femtosecond pulses would destroy the fibre material, and non-linear dispersion effects would significantly change beam parameters. In contrast, photonic crystal fibres mainly guide the laser pulses in air, so that absorption and dispersive pulse broadening have essentially no effect. This article compares classical beam guidance with mirrors, lenses and prisms with photonic crystal fibres and describes the underlying concepts and the current state of technology. A classical mirror arm possesses more variable optical properties, while the HCF (Hollow-Core Photonic Crystal Fibre) must be matched in terms of the laser energy and the laser spectrum. In contrast, the HCF has more advantages in respect of handling, system integration and costs. For applications based on photodisruptive laser-tissue interaction, the relatively low damage threshold of photonic crystal fibres compared to classic beam guiding systems is unacceptable. If, however, pulsed laser radiation has a sufficiently low peak intensity, e.g. as used for plasma-induced ablation, photonic crystal fibres can definitely be considered as an alternative solution to classic beam guidance. Georg Thieme Verlag KG Stuttgart · New York.

FEL (Free Electron Laser) Optics Coating Test Program (Design Phase of Sample Introduction Chamber)

DTIC Science & Technology

1986-02-01

is the photon energy dependent on the molecular species? - does the saturation depend on the UV photon energy? 3. Examine the rapid, saturating...can also be determined if the active photon energy range depends significantly on the molecular species. In a six month program, the first three...determine if the deposition rate depends #significantly on the species. The photon energy dependence of the deposition rate on the molecular species

Magnetoresponsive discoidal photonic crystals toward active color pigments.

PubMed

Lee, Hye Soo; Kim, Ju Hyeon; Lee, Joon-Seok; Sim, Jae Young; Seo, Jung Yoon; Oh, You-Kwan; Yang, Seung-Man; Kim, Shin-Hyun

2014-09-03

Photonic microdisks with a multilayered structure are designed from photocurable suspensions by step-by-step photolithography. In each step of photolithography, either a colloidal photonic crystal or a magnetic-particle-laden layer is stacked over the windows of a photomask. Sequential photolithography enables the creation of multilayered photonic microdisks that have brilliant structural colors that can be switched by an external magnetic field. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Differences in Normal Tissue Response in the Esophagus Between Proton and Photon Radiation Therapy for Non-Small Cell Lung Cancer Using In Vivo Imaging Biomarkers.

PubMed

Niedzielski, Joshua S; Yang, Jinzhong; Mohan, Radhe; Titt, Uwe; Mirkovic, Dragan; Stingo, Francesco; Liao, Zhongxing; Gomez, Daniel R; Martel, Mary K; Briere, Tina M; Court, Laurence E

2017-11-15

To determine whether there exists any significant difference in normal tissue toxicity between intensity modulated radiation therapy (IMRT) or proton therapy for the treatment of non-small cell lung cancer. A total of 134 study patients (n=49 treated with proton therapy, n=85 with IMRT) treated in a randomized trial had a previously validated esophageal toxicity imaging biomarker, esophageal expansion, quantified during radiation therapy, as well as esophagitis grade (Common Terminology Criteria for Adverse Events version 3.0), on a weekly basis during treatment. Differences between the 2 modalities were statically analyzed using the imaging biomarker metric value (Kruskal-Wallis analysis of variance), as well as the incidence and severity of esophagitis grade (χ 2 and Fisher exact tests, respectively). The dose-response of the imaging biomarker was also compared between modalities using esophageal equivalent uniform dose, as well as delivered dose to an isotropic esophageal subvolume. No statistically significant difference in the distribution of esophagitis grade, the incidence of grade ≥3 esophagitis (15 and 11 patients treated with IMRT and proton therapy, respectively), or the esophageal expansion imaging biomarker between cohorts (P>.05) was found. The distribution of imaging biomarker metric values had similar distributions between treatment arms, despite a slightly higher dose volume in the proton arm (P>.05). Imaging biomarker dose-response was similar between modalities for dose quantified as esophageal equivalent uniform dose and delivered esophageal subvolume dose. Regardless of treatment modality, there was high variability in imaging biomarker response, as well as esophagitis grade, for similar esophageal doses between patients. There was no significant difference in esophageal toxicity from either proton- or photon-based radiation therapy as quantified by esophagitis grade or the esophageal expansion imaging biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

Review and history of photon cross section calculations.

PubMed

Hubbell, J H

2006-07-07

Photon (x-ray, gamma-ray, bremsstrahlung) mass attenuation coefficients, mu/rho, are among the most widely used physical parameters employed in medical diagnostic and therapy computations, as well as in diverse applications in other fields such as nuclear power plant shielding, health physics and industrial irradiation and monitoring, and in x-ray crystallography. This review traces the evolution of this data base from its empirical beginnings totally derived from measurements beginning in 1907 by Barkla and Sadler and continuing up through the 1935 Allen compilation (published virtually unchanged in all editions up through 1971-1972 of the Chemical Rubber Handbook), to the 1949 semi-empirical compilation of Victoreen, as our theoretical understanding of the constituent Compton scattering, photoabsorption and pair production interactions of photons with atoms became more quantitative. The 1950s saw the advent of completely theoretical (guided by available measured data) systematic compilations such as in the works of Davisson and Evans, and by White-Grodstein under the direction of Fano, using mostly theory developed in the 1930s (pre-World War II) by Sauter, Bethe, Heitler and others. Post-World War II new theoretical activity, and the introduction of the electronic automatic computer, led to the more extensive and more accurate compilations in the 1960s and 1970s by Storm and Israel, and by Berger and Hubbell. Today's mu/rho compilations by Cullen et al, by Seltzer, Berger and Hubbell, and by others, collectively spanning the ten decades of photon energy from 10 eV to 100 GeV, for all elements Z= 1 to 100, draw heavily on the 1970s shell-by-shell photoabsorption computations of Scofield, the 1960s coherent and incoherent scattering computations of Cromer et al, and the 1980 computations of electron-positron pair and triplet computations of Hubbell, Gimm and Øverbø, these names being representative of the vast legions of other researchers whose work fed into these computations.

REVIEW: Review and history of photon cross section calculations

NASA Astrophysics Data System (ADS)

Hubbell, J. H.

2006-07-01

Photon (x-ray, gamma-ray, bremsstrahlung) mass attenuation coefficients, μ/ρ, are among the most widely used physical parameters employed in medical diagnostic and therapy computations, as well as in diverse applications in other fields such as nuclear power plant shielding, health physics and industrial irradiation and monitoring, and in x-ray crystallography. This review traces the evolution of this data base from its empirical beginnings totally derived from measurements beginning in 1907 by Barkla and Sadler and continuing up through the 1935 Allen compilation (published virtually unchanged in all editions up through 1971-1972 of the Chemical Rubber Handbook), to the 1949 semi-empirical compilation of Victoreen, as our theoretical understanding of the constituent Compton scattering, photoabsorption and pair production interactions of photons with atoms became more quantitative. The 1950s saw the advent of completely theoretical (guided by available measured data) systematic compilations such as in the works of Davisson and Evans, and by White-Grodstein under the direction of Fano, using mostly theory developed in the 1930s (pre-World War II) by Sauter, Bethe, Heitler and others. Post-World War II new theoretical activity, and the introduction of the electronic automatic computer, led to the more extensive and more accurate compilations in the 1960s and 1970s by Storm and Israel, and by Berger and Hubbell. Today's μ/ρ compilations by Cullen et al, by Seltzer, Berger and Hubbell, and by others, collectively spanning the ten decades of photon energy from 10 eV to 100 GeV, for all elements Z= 1 to 100, draw heavily on the 1970s shell-by-shell photoabsorption computations of Scofield, the 1960s coherent and incoherent scattering computations of Cromer et al, and the 1980 computations of electron-positron pair and triplet computations of Hubbell, Gimm and Øverbø, these names being representative of the vast legions of other researchers whose work fed into these computations. Work supported by the National Institute of Standards and Technology.

Compton Camera and Prompt Gamma Ray Timing: Two Methods for In Vivo Range Assessment in Proton Therapy

PubMed Central

Hueso-González, Fernando; Fiedler, Fine; Golnik, Christian; Kormoll, Thomas; Pausch, Guntram; Petzoldt, Johannes; Römer, Katja E.; Enghardt, Wolfgang

2016-01-01

Proton beams are promising means for treating tumors. Such charged particles stop at a defined depth, where the ionization density is maximum. As the dose deposit beyond this distal edge is very low, proton therapy minimizes the damage to normal tissue compared to photon therapy. Nevertheless, inherent range uncertainties cast doubts on the irradiation of tumors close to organs at risk and lead to the application of conservative safety margins. This constrains significantly the potential benefits of protons over photons. In this context, several research groups are developing experimental tools for range verification based on the detection of prompt gammas, a nuclear by-product of the proton irradiation. At OncoRay and Helmholtz-Zentrum Dresden-Rossendorf, detector components have been characterized in realistic radiation environments as a step toward a clinical Compton camera. On the one hand, corresponding experimental methods and results obtained during the ENTERVISION training network are reviewed. On the other hand, a novel method based on timing spectroscopy has been proposed as an alternative to collimated imaging systems. The first tests of the timing method at a clinical proton accelerator are summarized, its applicability in a clinical environment for challenging the current safety margins is assessed, and the factors limiting its precision are discussed. PMID:27148473

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.

Breast conserving treatment for breast cancer: dosimetric comparison of sequential versus simultaneous integrated photon boost.

PubMed

Van Parijs, Hilde; Reynders, Truus; Heuninckx, Karina; Verellen, Dirk; Storme, Guy; De Ridder, Mark

2014-01-01

Breast conserving surgery followed by whole breast irradiation is widely accepted as standard of care for early breast cancer. Addition of a boost dose to the initial tumor area further reduces local recurrences. We investigated the dosimetric benefits of a simultaneously integrated boost (SIB) compared to a sequential boost to hypofractionate the boost volume, while maintaining normofractionation on the breast. For 10 patients 4 treatment plans were deployed, 1 with a sequential photon boost, and 3 with different SIB techniques: on a conventional linear accelerator, helical TomoTherapy, and static TomoDirect. Dosimetric comparison was performed. PTV-coverage was good in all techniques. Conformity was better with all SIB techniques compared to sequential boost (P = 0.0001). There was less dose spilling to the ipsilateral breast outside the PTVboost (P = 0.04). The dose to the organs at risk (OAR) was not influenced by SIB compared to sequential boost. Helical TomoTherapy showed a higher mean dose to the contralateral breast, but less than 5 Gy for each patient. SIB showed less dose spilling within the breast and equal dose to OAR compared to sequential boost. Both helical TomoTherapy and the conventional technique delivered acceptable dosimetry. SIB seems a safe alternative and can be implemented in clinical routine.

Breast Conserving Treatment for Breast Cancer: Dosimetric Comparison of Sequential versus Simultaneous Integrated Photon Boost

PubMed Central

Reynders, Truus; Heuninckx, Karina; Verellen, Dirk; Storme, Guy; De Ridder, Mark

2014-01-01

Background. Breast conserving surgery followed by whole breast irradiation is widely accepted as standard of care for early breast cancer. Addition of a boost dose to the initial tumor area further reduces local recurrences. We investigated the dosimetric benefits of a simultaneously integrated boost (SIB) compared to a sequential boost to hypofractionate the boost volume, while maintaining normofractionation on the breast. Methods. For 10 patients 4 treatment plans were deployed, 1 with a sequential photon boost, and 3 with different SIB techniques: on a conventional linear accelerator, helical TomoTherapy, and static TomoDirect. Dosimetric comparison was performed. Results. PTV-coverage was good in all techniques. Conformity was better with all SIB techniques compared to sequential boost (P = 0.0001). There was less dose spilling to the ipsilateral breast outside the PTVboost (P = 0.04). The dose to the organs at risk (OAR) was not influenced by SIB compared to sequential boost. Helical TomoTherapy showed a higher mean dose to the contralateral breast, but less than 5 Gy for each patient. Conclusions. SIB showed less dose spilling within the breast and equal dose to OAR compared to sequential boost. Both helical TomoTherapy and the conventional technique delivered acceptable dosimetry. SIB seems a safe alternative and can be implemented in clinical routine. PMID:25162031

The development and validation of a Monte Carlo model for calculating the out-of-field dose from radiotherapy treatments

NASA Astrophysics Data System (ADS)

Kry, Stephen

Introduction. External beam photon radiotherapy is a common treatment for many malignancies, but results in the exposure of the patient to radiation away from the treatment site. This out-of-field radiation irradiates healthy tissue and may lead to the induction of secondary malignancies. Out-of-field radiation is composed of photons and, at high treatment energies, neutrons. Measurement of this out-of-field dose is time consuming, often difficult, and is specific to the conditions of the measurements. Monte Carlo simulations may be a viable approach to determining the out-of-field dose quickly, accurately, and for arbitrary irradiation conditions. Methods. An accelerator head, gantry, and treatment vault were modeled with MCNPX and 6 MV and 18 MV beams were simulated. Photon doses were calculated in-field and compared to measurements made with an ion chamber in a water tank. Photon doses were also calculated out-of-field from static fields and compared to measurements made with thermoluminescent dosimeters in acrylic. Neutron fluences were calculated and compared to measurements made with gold foils. Finally, photon and neutron dose equivalents were calculated in an anthropomorphic phantom following intensity-modulated radiation therapy and compared to previously published dose equivalents. Results. The Monte Carlo model was able to accurately calculate the in-field dose. From static treatment fields, the model was also able to calculate the out-of-field photon dose within 16% at 6 MV and 17% at 18 MV and the neutron fluence within 19% on average. From the simulated IMRT treatments, the calculated out-of-field photon dose was within 14% of measurement at 6 MV and 13% at 18 MV on average. The calculated neutron dose equivalent was much lower than the measured value but is likely accurate because the measured neutron dose equivalent was based on an overestimated neutron energy. Based on the calculated out-of-field doses generated by the Monte Carlo model, it was possible to estimate the risk of fatal secondary malignancy, which was consistent with previous estimates except for the neutron discrepancy. Conclusions. The Monte Carlo model developed here is well suited to studying the out-of-field dose equivalent from photons and neutrons under a variety of irradiation configurations, including complex treatments on complex phantoms. Based on the calculated dose equivalents, it is possible to estimate the risk of secondary malignancy associated with out-of-field doses. The Monte Carlo model should be used to study, quantify, and minimize the out-of-field dose equivalent and associated risks received by patients undergoing radiation therapy.

Dosimetric characteristics with spatial fractionation using electron grid therapy.

PubMed

Meigooni, A S; Parker, S A; Zheng, J; Kalbaugh, K J; Regine, W F; Mohiuddin, M

2002-01-01

Recently, promising clinical results have been shown in the delivery of palliative treatments using megavoltage photon grid therapy. However, the use of megavoltage photon grid therapy is limited in the treatment of bulky superficial lesions where critical radiosensitive anatomical structures are present beyond tumor volumes. As a result, spatially fractionated electron grid therapy was investigated in this project. Dose distributions of 1.4-cm-thick cerrobend grid blocks were experimentally determined for electron beams ranging from 6 to 20 MeV. These blocks were designed and fabricated at out institution to fit into a 20 x 20-cm(2) electron cone of a commercially available linear accelerator. Beam profiles and percentage depth dose (PDD) curves were measured in Solid Water phantom material using radiographic film, LiF TLD, and ionometric techniques. Open-field PDD curves were compared with those of single holes grid with diameters of 1.5, 2.0, 2.5, 3.0, and 3.5 cm to find the optimum diameter. A 2.5-cm hole diameter was found to be the optimal size for all electron energies between 6 and 20 MeV. The results indicate peak-to-valley ratios decrease with depth and the largest ratio is found at Dmax. Also, the TLD measurements show that the dose under the blocked regions of the grid ranged from 9.7% to 39% of the dose beneath the grid holes, depending on the measurement location and beam energy.

Collaborative Research. Atmospheric Pressure Microplasma Chemistry-Photon Synergies

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

Park, Sung-Jin; Eden, James Gary

Combining the effects of low temperature, atmospheric pressure microplasmas and microplasma photon sources offers the promise of greatly expanding the range of applications for each of them. The plasma sources create active chemical species and these can be activated further by the addition of photons and the associated photochemistry. There are many ways to combine the effects of plasma chemistry and photochemistry, especially if there are multiple phases present. This project combined the construction of appropriate test experimental systems, various spectroscopic diagnostics and mathematical modeling. Through a continuous discussion and co-design process with the UC-Berkeley Team, we have successfully completedmore » the fabrication and testing of all components for a microplasma array-assisted system designed for photon-activated plasma chemistry research. Microcavity plasma lamps capable of generating more than 20 mW/cm 2 at 172 nm (Xe dimer) were fabricated with a custom form factor to mate to the plasma chemistry setup, and a lamp was current being installed by the Berkeley team so as to investigate plasma chemistry-photon synergies at a higher photon energy (~7.2 eV) as compared to the UVA treatment that is afforded by UV LEDs operating at 365 nm. In particular, motivated by the promising results from the Berkeley team with UVA treatment, we also produced the first generation of lamps that can generate photons in the 300-370 nm wavelength range. Another set of experiments, conducted under the auspices of this grant, involved the use of plasma microjet arrays. The combination of the photons and excited radicals produced by the plasma column resulted in broad area deactivation of bacteria.« less

Electro-optic routing of photons from a single quantum dot in photonic integrated circuits

NASA Astrophysics Data System (ADS)

Midolo, Leonardo; Hansen, Sofie L.; Zhang, Weili; Papon, Camille; Schott, Rüdiger; Ludwig, Arne; Wieck, Andreas D.; Lodahl, Peter; Stobbe, Søren

2017-12-01

Recent breakthroughs in solid-state photonic quantum technologies enable generating and detecting single photons with near-unity efficiency as required for a range of photonic quantum technologies. The lack of methods to simultaneously generate and control photons within the same chip, however, has formed a main obstacle to achieving efficient multi-qubit gates and to harness the advantages of chip-scale quantum photonics. Here we propose and demonstrate an integrated voltage-controlled phase shifter based on the electro-optic effect in suspended photonic waveguides with embedded quantum emitters. The phase control allows building a compact Mach-Zehnder interferometer with two orthogonal arms, taking advantage of the anisotropic electro-optic response in gallium arsenide. Photons emitted by single self-assembled quantum dots can be actively routed into the two outputs of the interferometer. These results, together with the observed sub-microsecond response time, constitute a significant step towards chip-scale single-photon-source de-multiplexing, fiber-loop boson sampling, and linear optical quantum computing.

Surface modification of nanoporous anodic alumina photonic crystals for photocatalytic applications

NASA Astrophysics Data System (ADS)

Lim, Siew Yee; Law, Cheryl Suwen; Santos, Abel

2018-01-01

Herein, we report on the development of a rationally designed composite photocatalyst material by combining nanoporous anodic alumina-rugate filters (NAA-RFs) with photo-active layers of titanium dioxide (TiO2). NAA-RFs are synthesised by sinusoidal pulse anodisation and subsequently functionalised with TiO2 by sol-gel method to provide the photonic structures with photocatalytic properties. We demonstrate that the characteristic photonic stopband (PSB) of the surface-modified NAA-RFs can be precisely tuned across the UV-visible-NIR spectrum to enhance the photon-toelectron conversion of TiO2 by `slow photon effect'. We systematically investigate the effect of the anodisation parameters (i.e. anodisation period and pore widening time) on the position of the PSB of NAA-RFs as well as the photocatalytic performances displayed by these photonic crystal structures. When the edges of the PSB of surfacemodified NAA-RFs are positioned closely to the absorption peak of the model organic dye (i.e. methyl orange - MO), the photocatalytic performance of the system to degrade these molecules is enhanced under simulated solar light irradiation due to slow photon effect. Our investigation also reveals that the photocatalytic activity of surface-modified NAA-RFs is independent of slow photon effect and enhances with increasing period length (i.e. increasing anodisation period) of the photonic structures when there is no overlap between the PSB and the absorption peak of MO. This study therefore provides a rationale towards the photocatalytic enhancement of photonic crystals by a rational design of the PSB, creating new opportunities for the future development of high-performance photocatalysts.

Thermophotovoltaic in-situ mirror cell

DOEpatents

Campbell, Brian C.

1997-01-01

A photovoltaic cell used in a direct energy conversion generator for converting heat to electricity includes a reflective layer disposed within the cell between the active layers of the cell and the cell substrate. The reflective layer reflects photons of low energy back to a photon producing emitter for reabsorption by the emitter, or reflects photons with energy greater than the cell bandgap back to the cell active layers for conversion into electricity. The reflective layer can comprise a reflective metal such as gold while the substrate can comprise heavily doped silicon or a metal.

Piezoelectrically enhanced photocathode

NASA Technical Reports Server (NTRS)

Beach, Robert A. (Inventor); Nikzad, Shouleh (Inventor); Strittmatter, Robert P. (Inventor); Bell, Lloyd Douglas (Inventor)

2009-01-01

A photocathode, for generating electrons in response to incident photons in a photodetector, includes a base layer having a first lattice structure and an active layer having a second lattice structure and epitaxially formed on the base layer, the first and second lattice structures being sufficiently different to create a strain in the active layer with a corresponding piezoelectrically induced polarization field in the active layer, the active layer having a band gap energy corresponding to a desired photon energy.

Electric field induced structural colour tuning of a silver/titanium dioxide nanoparticle one-dimensional photonic crystal

PubMed Central

Aluicio-Sarduy, Eduardo; Callegari, Simone; Figueroa del Valle, Diana Gisell; Desii, Andrea; Kriegel, Ilka

2016-01-01

Summary An electric field is employed for the active tuning of the structural colour in photonic crystals, which acts as an effective external stimulus with an impact on light transmission manipulation. In this work, we demonstrate structural colour in a photonic crystal device comprised of alternating layers of silver nanoparticles and titanium dioxide nanoparticles, exhibiting spectral shifts of around 10 nm for an applied voltage of only 10 V. The accumulation of charge at the metal/dielectric interface with an applied electric field leads to an effective increase of the charges contributing to the plasma frequency in silver. This initiates a blue shift of the silver plasmon band with a simultaneous blue shift of the photonic band gap as a result of the change in the silver dielectric function (i.e. decrease of the effective refractive index). These results are the first demonstration of active colour tuning in silver/titanium dioxide nanoparticle-based photonic crystals and open the route to metal/dielectric-based photonic crystals as electro-optic switches. PMID:27826514

Electric field induced structural colour tuning of a silver/titanium dioxide nanoparticle one-dimensional photonic crystal.

PubMed

Aluicio-Sarduy, Eduardo; Callegari, Simone; Figueroa Del Valle, Diana Gisell; Desii, Andrea; Kriegel, Ilka; Scotognella, Francesco

2016-01-01

An electric field is employed for the active tuning of the structural colour in photonic crystals, which acts as an effective external stimulus with an impact on light transmission manipulation. In this work, we demonstrate structural colour in a photonic crystal device comprised of alternating layers of silver nanoparticles and titanium dioxide nanoparticles, exhibiting spectral shifts of around 10 nm for an applied voltage of only 10 V. The accumulation of charge at the metal/dielectric interface with an applied electric field leads to an effective increase of the charges contributing to the plasma frequency in silver. This initiates a blue shift of the silver plasmon band with a simultaneous blue shift of the photonic band gap as a result of the change in the silver dielectric function (i.e. decrease of the effective refractive index). These results are the first demonstration of active colour tuning in silver/titanium dioxide nanoparticle-based photonic crystals and open the route to metal/dielectric-based photonic crystals as electro-optic switches.

Plasma emission spectroscopy method of tumor therapy

DOEpatents

Fleming, Kevin J.

1997-01-01

Disclosed are a method and apparatus for performing photon diagnostics using a portable and durable apparatus which incorporates the use of a remote sensing probe in fiberoptic communication with an interferometer or spectrometer. Also disclosed are applications for the apparatus including optically measuring high velocities and analyzing plasma/emission spectral characteristics.

Thiamazole Pretreatment Lowers the (131)I Activity Needed to Cure Hyperthyroidism in Patients With Nodular Goiter.

PubMed

Kyrilli, Aglaia; Tang, Bich-Ngoc-Thanh; Huyge, Valérie; Blocklet, Didier; Goldman, Serge; Corvilain, Bernard; Moreno-Reyes, Rodrigo

2015-06-01

Relatively low radioiodine uptake (RAIU) represents a common obstacle for radioiodine ((131)I) therapy in patients with multinodular goiter complicated by hyperthyroidism. To evaluate whether thiamazole (MTZ) pretreatment can increase (131)I therapeutic efficacy. Twenty-two patients with multinodular goiter, subclinical hyperthyroidism, and RAIU < 50% were randomized to receive either a low-iodine diet (LID; n = 10) or MTZ 30 mg/d (n = 12) for 42 days. Thyroid function and 24-hour RAIU were measured before and after treatment. Thyroid volume was evaluated by either magnetic resonance imaging or single photon emission computed tomography. Mean 24-hour RAIU increased significantly from 32 ± 10% to 63 ± 18% in the MTZ group (P < .001). Consequently, there was a 31% decrease in the calculated median therapeutic (131)I activity after MTZ (P < .05). No significant changes in 24-hour RAIU were observed after diet. In the MTZ group, median serum TSH levels increased significantly by 9% and mean serum free T4 and free T3 concentrations decreased by 22% and 15%, respectively, whereas no changes in thyroid function were observed in the LID group. Thyroid volume did not significantly change in either of the two groups. At 12 months after radioiodine treatment, median serum TSH was within the normal range in both groups. MTZ treatment before (131)I therapy resulted in an average 2-fold increase in thyroid RAIU and enhanced the efficiency of radioiodine therapy assessed at 12 months. MTZ pretreatment is therefore a safe, easily accessible alternative to recombinant human TSH stimulation and a more effective option than LID.

Low-noise low-jitter 32-pixels CMOS single-photon avalanche diodes array for single-photon counting from 300 nm to 900 nm

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

Scarcella, Carmelo; Tosi, Alberto, E-mail: alberto.tosi@polimi.it; Villa, Federica

2013-12-15

We developed a single-photon counting multichannel detection system, based on a monolithic linear array of 32 CMOS SPADs (Complementary Metal-Oxide-Semiconductor Single-Photon Avalanche Diodes). All channels achieve a timing resolution of 100 ps (full-width at half maximum) and a photon detection efficiency of 50% at 400 nm. Dark count rate is very low even at room temperature, being about 125 counts/s for 50 μm active area diameter SPADs. Detection performance and microelectronic compactness of this CMOS SPAD array make it the best candidate for ultra-compact time-resolved spectrometers with single-photon sensitivity from 300 nm to 900 nm.

Feasibility study on the use of uranium in photoneutron target and BSA optimization for Linac based BNCT

NASA Astrophysics Data System (ADS)

Rahmani, Faezeh; Shahriari, Majid; Minoochehr, Abdolhamid; Nedaie, Hasan

2011-06-01

A hybrid photoneutron target including natural uranium has been studied for a 20 MeV linear electron accelerator (Linac) based Boron Neutron Capture Therapy (BNCT) facility. In this study the possibility of using uranium to increase the neutron intensity has been investigated by focusing on the time dependence behavior of the build-up and decay of the delayed gamma rays from fission fragments and activation products through photo-fission reactions in the BSA (Beam Shaping Assembly) configuration design. Delayed components of neutrons and photons were calculated. The obtained BSA parameters are in agreement with the IAEA recommendation and compared to the hybrid photoneutron target without U. The epithermal flux in the suggested design is 2.67E9 (n/cm 2s/mA).

Development of a Compton camera for prompt-gamma medical imaging

NASA Astrophysics Data System (ADS)

Aldawood, S.; Thirolf, P. G.; Miani, A.; Böhmer, M.; Dedes, G.; Gernhäuser, R.; Lang, C.; Liprandi, S.; Maier, L.; Marinšek, T.; Mayerhofer, M.; Schaart, D. R.; Lozano, I. Valencia; Parodi, K.

2017-11-01

A Compton camera-based detector system for photon detection from nuclear reactions induced by proton (or heavier ion) beams is under development at LMU Munich, targeting the online range verification of the particle beam in hadron therapy via prompt-gamma imaging. The detector is designed to be capable to reconstruct the photon source origin not only from the Compton scattering kinematics of the primary photon, but also to allow for tracking of the secondary Compton-scattered electrons, thus enabling a γ-source reconstruction also from incompletely absorbed photon events. The Compton camera consists of a monolithic LaBr3:Ce scintillation crystal, read out by a multi-anode PMT acting as absorber, preceded by a stacked array of 6 double-sided silicon strip detectors as scatterers. The detector components have been characterized both under offline and online conditions. The LaBr3:Ce crystal exhibits an excellent time and energy resolution. Using intense collimated 137Cs and 60Co sources, the monolithic scintillator was scanned on a fine 2D grid to generate a reference library of light amplitude distributions that allows for reconstructing the photon interaction position using a k-Nearest Neighbour (k-NN) algorithm. Systematic studies were performed to investigate the performance of the reconstruction algorithm, revealing an improvement of the spatial resolution with increasing photon energy to an optimum value of 3.7(1)mm at 1.33 MeV, achieved with the Categorical Average Pattern (CAP) modification of the k-NN algorithm.

Hybrid Integrated Platforms for Silicon Photonics

PubMed Central

Liang, Di; Roelkens, Gunther; Baets, Roel; Bowers, John E.

2010-01-01

A review of recent progress in hybrid integrated platforms for silicon photonics is presented. Integration of III-V semiconductors onto silicon-on-insulator substrates based on two different bonding techniques is compared, one comprising only inorganic materials, the other technique using an organic bonding agent. Issues such as bonding process and mechanism, bonding strength, uniformity, wafer surface requirement, and stress distribution are studied in detail. The application in silicon photonics to realize high-performance active and passive photonic devices on low-cost silicon wafers is discussed. Hybrid integration is believed to be a promising technology in a variety of applications of silicon photonics.

Method for photon activation positron annihilation analysis

DOEpatents

Akers, Douglas W.

2006-06-06

A non-destructive testing method comprises providing a specimen having at least one positron emitter therein; determining a threshold energy for activating the positron emitter; and determining whether a half-life of the positron emitter is less than a selected half-life. If the half-life of the positron emitter is greater than or equal to the selected half-life, then activating the positron emitter by bombarding the specimen with photons having energies greater than the threshold energy and detecting gamma rays produced by annihilation of positrons in the specimen. If the half-life of the positron emitter is less then the selected half-life, then alternately activating the positron emitter by bombarding the specimen with photons having energies greater then the threshold energy and detecting gamma rays produced by positron annihilation within the specimen.

COST-ENLIGHT strategic workshop on hadron (particle) therapy, CERN, Geneva, 3-4 May 2007.

PubMed

Taylor, R E

2008-03-01

This meeting was convened by COST (Co-operation in the Field of Scientific and Technical Research) and ENLIGHT (European Network for Research in Light-Ion Hadron Therapy) to review the current status of hadron therapy in Europe. The aims were to increase awareness of hadron therapy within the scientific community, to produce a document outlining the present and future prospects for this treatment modality and to bring together hadron therapy scientists and clinicians. Proton therapy offers the potential for therapeutic gain from dose distribution advantages when compared with photon therapy. Carbon ion therapy, by nature of its higher linear energy transfer (LET) and relative biological effectiveness (RBE), may further improve local control. A further potential benefit of carbon ion therapy is the ability to deliver hypofractionated radiotherapy. A further aim of this meeting was to commence preparation of a programme of work packages with a view to submitting an application for European Union funding within the FP7 programme. This comprises a series of seven work packages, which will be a focus for European collaboration.

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

Gotman, Irena, E-mail: gotman@technion.ac.il; Gutmanas, Elazar Y., E-mail: gutmanas@technion.ac.il; Tomsk Polytechnic University, Tomsk, 634050

Continuous research activities in the field of nanomedicine in the past decade have, to a great extent, been focused on nanoparticle technologies for cancer therapy. Gold and iron oxide nanoparticles (NP) are two of the most studied inorganic nanomaterials due to their unique optical and magnetic properties. Both types of NPs are emerging as promising systems for anti-tumor drug delivery and for nanoparticle-mediated thermal therapy of cancer. In thermal therapy, localized heating inside tumors or in proximity of tumor cells can be induced, for example, with Au NPs by radiofrequency ablation heating or conversion of photon energy (photothermal therapy) andmore » in iron oxide magnetic NPs by heat generation through relaxation in an alternating magnetic field (magnetic hyperthermia). Furthermore, the superparamagnetic properties of iron oxide nanoparticles have led to their use as potent MRI (magnetic resonance imaging) contrast agents. Surface modification/coating can produce NPs with tailored and desired properties, such as enhanced blood circulation time, stability, biocompatibility and water solubility. To target nanoparticles to specific tumor cells, NPs should be conjugated with targeting moieties on the surface which bind to receptors or other molecular structures on the cell surface. The article presents several approaches to enhancing the specificity of Au and iron oxide nanoparticles for tumor tissue by appropriate surface modification/functionalization, as well as the effect of these treatments on the saturation magnetization value of iron oxide NPs. The use of other nanoparticles and nanostructures in cancer treatment is also briefly reviewed.« less

Molecular Imaging and Radionuclide Therapy of Melanoma Targeting the Melanocortin 1 Receptor

PubMed Central

Zhang, Chengcheng; Lin, Kuo-Shyan; Bénard, François

2017-01-01

Melanoma is a deadly disease at late metastatic stage, and early diagnosis and accurate staging remain the key aspects for managing melanoma. The melanocortin 1 receptor (MC1 R) is overexpressed in primary and metastatic melanomas, and its endogenous ligand, the α-melanocyte-stimulating hormone (αMSH), has been extensively studied for the development of MC1 R-targeted molecular imaging and therapy of melanoma. Natural αMSH is not well suited for this purpose due to low stability in vivo. Unnatural amino acid substitutions substantially stabilized the peptide, while cyclization via lactam bridge and metal coordination further improved binding affinity and stability. In this study, we summarized the development and the in vitro and in vivo characteristics of the radiolabeled αMSH analogues, including 99mTc-, 111In-, 67 Ga-, or 125I-labeled αMSH analogues for imaging with single-photon emission computed tomography; 68Ga-, 64Cu-, or 18F-labeled αMSH analogues for imaging with positron emission tomography; and 188Re-, 177Lu-, 90Y-, or 212Pb-labeled αMSH analogues for radionuclide therapy. These radiolabeled αMSH analogues showed promising results with high tumor uptake and rapid normal tissue activity clearance in the preclinical model of B16F1 and B16F10 mouse melanomas. These results highlight the potential of using radiolabeled αMSH analogues in clinical applications for molecular imaging and radionuclide therapy of melanoma. PMID:29182034

Optimization in Radiation Therapy: Applications in Brachytherapy and Intensity Modulated Radiation Therapy

NASA Astrophysics Data System (ADS)

McGeachy, Philip David

Over 50% of cancer patients require radiation therapy (RT). RT is an optimization problem requiring maximization of the radiation damage to the tumor while minimizing the harm to the healthy tissues. This dissertation focuses on two main RT optimization problems: 1) brachytherapy and 2) intensity modulated radiation therapy (IMRT). The brachytherapy research involved solving a non-convex optimization problem by creating an open-source genetic algorithm optimizer to determine the optimal radioactive seed distribution for a given set of patient volumes and constraints, both dosimetric- and implant-based. The optimizer was tested for a set of 45 prostate brachytherapy patients. While all solutions met the clinical standards, they also benchmarked favorably with those generated by a standard commercial solver. Compared to its compatriot, the salient features of the generated solutions were: slightly reduced prostate coverage, lower dose to the urethra and rectum, and a smaller number of needles required for an implant. Historically, IMRT requires modulation of fluence while keeping the photon beam energy fixed. The IMRT-related investigation in this thesis aimed at broadening the solution space by varying photon energy. The problem therefore involved simultaneous optimization of photon beamlet energy and fluence, denoted by XMRT. Formulating the problem as convex, linear programming was applied to obtain solutions for optimal energy-dependent fluences, while achieving all clinical objectives and constraints imposed. Dosimetric advantages of XMRT over single-energy IMRT in the improved sparing of organs at risk (OARs) was demonstrated in simplified phantom studies. The XMRT algorithm was improved to include clinical dose-volume constraints and clinical studies for prostate and head and neck cancer patients were investigated. Compared to IMRT, XMRT provided improved dosimetric benefit in the prostate case, particularly within intermediate- to low-dose regions (≤ 40 Gy) for OARs. For head and neck cases, XMRT solutions showed no significant disadvantage or advantage over IMRT. The deliverability concerns for the fluence maps generated from XMRT were addressed by incorporating smoothing constraints during the optimization and through successful generation of treatment machine files. Further research is needed to explore the full potential of the XMRT approach to RT.

Active integrated filters for RF-photonic channelizers.

PubMed

El Nagdi, Amr; Liu, Ke; LaFave, Tim P; Hunt, Louis R; Ramakrishna, Viswanath; Dabkowski, Mieczyslaw; MacFarlane, Duncan L; Christensen, Marc P

2011-01-01

A theoretical study of RF-photonic channelizers using four architectures formed by active integrated filters with tunable gains is presented. The integrated filters are enabled by two- and four-port nano-photonic couplers (NPCs). Lossless and three individual manufacturing cases with high transmission, high reflection, and symmetric couplers are assumed in the work. NPCs behavior is dependent upon the phenomenon of frustrated total internal reflection. Experimentally, photonic channelizers are fabricated in one single semiconductor chip on multi-quantum well epitaxial InP wafers using conventional microelectronics processing techniques. A state space modeling approach is used to derive the transfer functions and analyze the stability of these filters. The ability of adapting using the gains is demonstrated. Our simulation results indicate that the characteristic bandpass and notch filter responses of each structure are the basis of channelizer architectures, and optical gain may be used to adjust filter parameters to obtain a desired frequency magnitude response, especially in the range of 1-5 GHz for the chip with a coupler separation of ∼9 mm. Preliminarily, the measurement of spectral response shows enhancement of quality factor by using higher optical gains. The present compact active filters on an InP-based integrated photonic circuit hold the potential for a variety of channelizer applications. Compared to a pure RF channelizer, photonic channelizers may perform both channelization and down-conversion in an optical domain.

Structuring β-Ga2O3 photonic crystal photocatalyst for efficient degradation of organic pollutants.

PubMed

Li, Xiaofang; Zhen, Xiuzheng; Meng, Sugang; Xian, Jiangjun; Shao, Yu; Fu, Xianzhi; Li, Danzhen

2013-09-03

Coupling photocatalysts with photonic crystals structure is based on the unique property of photonic crystals in confining, controlling, and manipulating the incident photons. This combination enhances the light absorption in photocatalysts and thus greatly improves their photocatalytic performance. In this study, Ga2O3 photonic crystals with well-arranged skeleton structures were prepared via a dip-coating infiltration method. The positions of the electronic band absorption for Ga2O3 photonic crystals could be made to locate on the red edge, on the blue edge, and away from the edge of their photonic band gaps by changing the pore sizes of the samples, respectively. Particularly, the electronic band absorption of the Ga2O3 photonic crystal with a pore size of 135 nm was enhanced more than other samples by making it locate on the red edge of its photonic band gap, which was confirmed by the higher instantaneous photocurrent and photocatalytic activity for the degradation of various organic pollutants under ultraviolet light irradiation. Furthermore, the degradation mechanism over Ga2O3 photonic crystals was discussed. The design of Ga2O3 photonic crystals presents a prospective application of photonic crystals in photocatalysis to address light harvesting and quantum efficiency problems through manipulating photons or constructing photonic crystal structure as groundwork.

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.

The Physical Mechanism for Retinal Discrete Dark Noise: Thermal Activation or Cellular Ultraweak Photon Emission?

PubMed

Salari, Vahid; Scholkmann, Felix; Bokkon, Istvan; Shahbazi, Farhad; Tuszynski, Jack

2016-01-01

For several decades the physical mechanism underlying discrete dark noise of photoreceptors in the eye has remained highly controversial and poorly understood. It is known that the Arrhenius equation, which is based on the Boltzmann distribution for thermal activation, can model only a part (e.g. half of the activation energy) of the retinal dark noise experimentally observed for vertebrate rod and cone pigments. Using the Hinshelwood distribution instead of the Boltzmann distribution in the Arrhenius equation has been proposed as a solution to the problem. Here, we show that the using the Hinshelwood distribution does not solve the problem completely. As the discrete components of noise are indistinguishable in shape and duration from those produced by real photon induced photo-isomerization, the retinal discrete dark noise is most likely due to 'internal photons' inside cells and not due to thermal activation of visual pigments. Indeed, all living cells exhibit spontaneous ultraweak photon emission (UPE), mainly in the optical wavelength range, i.e., 350-700 nm. We show here that the retinal discrete dark noise has a similar rate as UPE and therefore dark noise is most likely due to spontaneous cellular UPE and not due to thermal activation.

Two photon spectroscopy and microscopy of the fluorescent flavoprotein, iLOV.

PubMed

Homans, Rachael J; Khan, Raja U; Andrews, Michael B; Kjeldsen, Annemette E; Natrajan, Louise S; Marsden, Steven; McKenzie, Edward A; Christie, John M; Jones, Alex R

2018-06-06

LOV-domains are ubiquitous photosensory proteins that are commonly re-engineered to serve as powerful and versatile fluorescent proteins and optogenetic tools. The photoactive, flavin chromophore, however, is excited using short wavelengths of light in the blue and UV regions, which have limited penetration into biological samples and can cause photodamage. Here, we have used non-linear spectroscopy and microscopy of the fluorescent protein, iLOV, to reveal that functional variants of LOV can be activated to great effect by two non-resonant photons of lower energy, near infrared light, not only in solution but also in biological samples. The two photon cross section of iLOV has a significantly blue-shifted S0 → S1 transition compared with the one photon absorption spectrum, suggesting preferential population of excited vibronic states. It is highly likely, therefore, that the two photon absorption wavelength of engineered, LOV-based tools is tuneable. We also demonstrate for the first time two photon imaging using iLOV in human epithelial kidney cells. Consequently, two photon absorption by engineered, flavin-based bio-molecular tools can enable non-invasive activation with high depth resolution and the potential for not only improved image clarity but also enhanced spatiotemporal control for optogenetic applications.

Chromophore absorbance change quantification in tissue during low-level light therapy

NASA Astrophysics Data System (ADS)

Huynh, Daniel; Chung, Christine; Qian, Li; Lilge, Lothar

2012-03-01

Low Level Light Therapy (LLLT) has been implicated to stimulate tissue, promoting healing and reducing pain. One of the potential pathways stimulated by LLLT relates to the electron transport chain, where photon quantum energy can induce a change in the biochemical reactions within the cell. The aim of this study is to assess the feasibility to exploit light additionally as a diagnostic tool to determine tissue physiological states, particularly in quantifying the changes in redox states of Cytochrome C as a result of induced LLLT biochemical reactions.

Cotard's syndrome with schizophreniform disorder can be successfully treated with electroconvulsive therapy: case report

PubMed Central

Caliyurt, Okan; Vardar, Erdal; Tuglu, Cengiz

2004-01-01

We report a case of Cotard's syndrome associated with psychotic symptoms. A 27-year-old man was admitted to hospital with the diagnosis of schizophreniform disorder. His presenting symptoms, which had started 1 month before hospital admission, were somatic delusions of gastrointestinal and cardiovascular malfunction and the absence of a stomach, which resulted in a decrease in weight from 75 kg to 63 kg in 1 month. Cranial computed tomographic images showed dilatation of the lateral and third ventricles, whereas magnetic resonance imaging revealed central atrophy and lateral ventricle dilatation. Single- photon emission computed tomography demonstrated left temporal, left frontal and left parietal hypoperfusion. The patient did not respond to antipsychotic therapies, but he was successfully treated with electroconvulsive therapy. This report emphasizes that Cotard's syndrome may be accompanied by lesions of the left hemisphere and that electroconvulsive therapy could be the first-line therapy in such patients with psychotic disorder. PMID:15069468

Continuously active interferometer stabilization and control for time-bin entanglement distribution

DOE PAGES

Toliver, Paul; Dailey, James M.; Agarwal, Anjali; ...

2015-02-10

In this study, we describe a new method enabling continuous stabilization and fine-level phase control of time-bin entanglement interferometers. Using this technique we demonstrate entangled photon transmission through 50 km of standard single-mode fiber. This technique reuses the entangled-pair generation pump which is co-propagated with the transmitted entangled photons. In addition, the co-propagating pump adds minimal noise to the entangled photons which are characterized by measuring a two-photon interference fringe.

Rational assembly of a biointerfaced core@shell nanocomplex towards selective and highly efficient synergistic photothermal/photodynamic therapy

NASA Astrophysics Data System (ADS)

Qin, Chenchen; Fei, Jinbo; Wang, Anhe; Yang, Yang; Li, Junbai

2015-11-01

To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular internalization and enhancement of endocytosis. Under one-time NIR two-photon illumination, AuNR-mediated hyperthermia can kill cancer cells directly. Meanwhile, the loaded photosensitizer, hypocrellin B, generates two kinds of reactive oxygen species (ROS) to induce cell apoptosis. Remarkably, hyperthermia can improve the yield of ROS. After intravenous injection of this bioconjugate into female BALB/c nude mice followed by laser irradiation (808 nm, 1.3 W cm-2, 6 min), the tumor growth is suppressed completely. The tumors are not recurrent within the observation time (19 days), and the normal or main organs are not obviously pathological. Thus, such a simplified and selective cancer treatment, combining photothermal and photodynamic therapy in a synergistic manner, provides outstanding efficiency in vivo. This nanocomplex with well-defined core@shell nanostructures integrated with a two-photon technique holds great promise to improve cancer phototherapy with a high efficiency in the clinic.To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular internalization and enhancement of endocytosis. Under one-time NIR two-photon illumination, AuNR-mediated hyperthermia can kill cancer cells directly. Meanwhile, the loaded photosensitizer, hypocrellin B, generates two kinds of reactive oxygen species (ROS) to induce cell apoptosis. Remarkably, hyperthermia can improve the yield of ROS. After intravenous injection of this bioconjugate into female BALB/c nude mice followed by laser irradiation (808 nm, 1.3 W cm-2, 6 min), the tumor growth is suppressed completely. The tumors are not recurrent within the observation time (19 days), and the normal or main organs are not obviously pathological. Thus, such a simplified and selective cancer treatment, combining photothermal and photodynamic therapy in a synergistic manner, provides outstanding efficiency in vivo. This nanocomplex with well-defined core@shell nanostructures integrated with a two-photon technique holds great promise to improve cancer phototherapy with a high efficiency in the clinic. Electronic supplementary information (ESI) available: The relevant TEM, DLS, UV spectra, photographs and chemical structures. See DOI: 10.1039/c5nr06501a

Blazar 3C 66A: Another extragalactic source of ultra-high-energy gamma-ray photons

NASA Astrophysics Data System (ADS)

Neshpor, Yu. I.; Stepanyan, A. A.; Kalekin, O. P.; Fomin, V. P.; Chalenko, N. N.; Shitov, V. G.

1998-03-01

he observations of the object 3C 66A which were carried out with the GT-48 gamma-ray telescope at the Crimean Astrophysical Observatory in November-December 1996 revealed a flux of ultra-high-energy (>10^12 eV) gamma-ray photons from this blazar. According to preliminary estimates, the photon flux is (31) 10^11 photons cm^-2 s^-1. The blazar 3C 66A is the third extragalactic object from which a flux of ultra- high-energy gamma-ray photons was detected. Fluxes of gamma-ray photons were previously detected from the galaxies Mk 421 and Mk 501 at the Whipple observatory. This result provides further evidence that active processes proceed in blazars which are accompanied by the generation of cosmic rays responsible for the emission of gamma-ray photons.

A fully reconfigurable photonic integrated signal processor

NASA Astrophysics Data System (ADS)

Liu, Weilin; Li, Ming; Guzzon, Robert S.; Norberg, Erik J.; Parker, John S.; Lu, Mingzhi; Coldren, Larry A.; Yao, Jianping

2016-03-01

Photonic signal processing has been considered a solution to overcome the inherent electronic speed limitations. Over the past few years, an impressive range of photonic integrated signal processors have been proposed, but they usually offer limited reconfigurability, a feature highly needed for the implementation of large-scale general-purpose photonic signal processors. Here, we report and experimentally demonstrate a fully reconfigurable photonic integrated signal processor based on an InP-InGaAsP material system. The proposed photonic signal processor is capable of performing reconfigurable signal processing functions including temporal integration, temporal differentiation and Hilbert transformation. The reconfigurability is achieved by controlling the injection currents to the active components of the signal processor. Our demonstration suggests great potential for chip-scale fully programmable all-optical signal processing.

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.

Iodine-131 imaging using 284 keV photons with a small animal CZT-SPECT system dedicated to low-medium-energy photon detection.

PubMed

Kojima, Akihiro; Gotoh, Kumiko; Shimamoto, Masako; Hasegawa, Koki; Okada, Seiji

2016-02-01

Iodine-131 is widely used for radionuclide therapy because of its β-particle and for diagnostic imaging employing its principal gamma ray. Since that principal gamma ray has the relatively high energy of 364 keV, small animal single-photon emission computed tomography (SPECT) imaging systems may be required to possess the ability to image such higher energy photons. The aim of this study was to investigate the possibility of imaging I-131 using its 284 keV photons instead of its 364 keV photons in a small animal SPECT imaging system dedicated to the detection of low-medium-energy photons (below 300 keV). The imaging system used was a commercially available preclinical SPECT instrument with CZT detectors that was equipped with multi-pinhole collimators and was accompanied by a CT imager. An energy window for I-131 imaging was set to a photopeak of 284 keV with a low abundance compared with 364 keV photons. Small line sources and two mice, one of each of two types, that were injected with NaI-131 were scanned. Although higher counts occurred at the peripheral region of the reconstructed images due to the collimator penetration by the 364 keV photons, the shape of the small line sources could be well visualized. The measured spatial resolution was relatively poor (~1.9 mm for full width at half maximum and ~3.9 mm for full width at tenth maximum). However, a good linear correlation between SPECT values and the level of I-131 radioactivity was observed. Furthermore, the uptake of NaI-131 to the thyroid gland for the two mice was clearly identified in the 3D-SPECT image fused with the X-ray CT image. We conclude that the use of an energy window set on the photopeak of 284 keV and the multi-pinhole collimator may permit I-131 imaging for a preclinical CZT-SPECT system that does not have the ability to acquire images using the 364 keV photons.

Variations in energy spectra and water-to-material stopping-power ratios in three-dimensional conformal and intensity-modulated photon fields

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

Jang, Si Young; Liu, H. Helen; Mohan, Radhe

Because of complex dose distributions and dose gradients that are created in three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiation therapy (IMRT), photon- and electron-energy spectra might change significantly with spatial locations and doses. This study examined variations in photon- and electron-energy spectra in 3D-CRT and IMRT photon fields. The effects of spectral variations on water-to-material stopping-power ratios used in Monte Carlo treatment planning systems and the responses of energy-dependent dosimeters, such as thermoluminescent dosimeters (TLDs) and radiographic films were further studied. The EGSnrc Monte Carlo code was used to simulate megavoltage 3D-CRT and IMRT photon fields. The photon- and electron-energymore » spectra were calculated in 3D water phantoms and anthropomorphic phantoms based on the fluence scored in voxel grids. We then obtained the water-to-material stopping-power ratios in the local voxels using the Spencer-Attix cavity theory. Changes in the responses of films and TLDs were estimated based on the calculated local energy spectra and published data on the dosimeter energy dependency. Results showed that the photon-energy spectra strongly depended on spatial positions and doses in both the 3D-CRT and IMRT fields. The relative fraction of low-energy photons (<100 keV) increased inversely with the photon dose in low-dose regions of the fields. A similar but smaller effect was observed for electrons in the phantoms. The maximum variation of the water-to-material stopping-power ratio over the range of calculated dose for both 3D-CRT and IMRT was negligible (<1.0%) for ICRU tissue, cortical bone, and soft bone and less than 3.6% for dry air and lung. Because of spectral softening at low doses, radiographic films in the phantoms could over-respond to dose by more than 30%, whereas the over-response of TLDs was less than 10%. Thus, spatial variations of the photon- and electron-energy spectra should be considered as important factors in 3D-CRT and IMRT dosimetry.« less

Paving the Road for Modern Particle Therapy - What Can We Learn from the Experience Gained with Fast Neutron Therapy in Munich?

PubMed

Specht, Hanno M; Neff, Teresa; Reuschel, Waltraud; Wagner, Franz M; Kampfer, Severin; Wilkens, Jan J; Petry, Winfried; Combs, Stephanie E

2015-01-01

While neutron therapy was a highly topical subject in the 70s and 80s, today there are only a few remaining facilities offering fast neutron therapy (FNT). Nevertheless, up to today more than 30,000 patients were treated with neutron therapy. For some indications like salivary gland tumors and malignant melanoma, there is clinical evidence that the addition of FNT leads to superior local control compared to photon treatment alone. FNT was available in Munich from 1985 until 2000 at the Reactor Neutron Therapy (RENT) facility. Patient treatment continued at the new research reactor FRM II in 2007 under improved treatment conditions, and today it can still be offered to selected patients as an individual treatment option. As there is a growing interest in high-linear energy transfer (LET) therapy with new hadron therapy centers emerging around the globe, the clinical data generated by neutron therapy might help to develop biologically driven treatment planning algorithms. Also FNT might experience its resurgence as a combinational partner of modern immunotherapies.

Paving the Road for Modern Particle Therapy – What Can We Learn from the Experience Gained with Fast Neutron Therapy in Munich?

PubMed Central

Specht, Hanno M.; Neff, Teresa; Reuschel, Waltraud; Wagner, Franz M.; Kampfer, Severin; Wilkens, Jan J.; Petry, Winfried; Combs, Stephanie E.

2015-01-01

While neutron therapy was a highly topical subject in the 70s and 80s, today there are only a few remaining facilities offering fast neutron therapy (FNT). Nevertheless, up to today more than 30,000 patients were treated with neutron therapy. For some indications like salivary gland tumors and malignant melanoma, there is clinical evidence that the addition of FNT leads to superior local control compared to photon treatment alone. FNT was available in Munich from 1985 until 2000 at the Reactor Neutron Therapy (RENT) facility. Patient treatment continued at the new research reactor FRM II in 2007 under improved treatment conditions, and today it can still be offered to selected patients as an individual treatment option. As there is a growing interest in high-linear energy transfer (LET) therapy with new hadron therapy centers emerging around the globe, the clinical data generated by neutron therapy might help to develop biologically driven treatment planning algorithms. Also FNT might experience its resurgence as a combinational partner of modern immunotherapies. PMID:26640777

Comparison of simulations with PHITS and HIBRAC with experimental data in the context of particle therapy monitoring

PubMed Central

Rohling, Heide; Sihver, Lembit; Priegnitz, Marlen; Enghardt, Wolfgang; Fiedler, Fine

2014-01-01

Therapeutic irradiation with protons and ions is advantageous over radiotherapy with photons due to its favorable dose deposition. Additionally, ion beams provide a higher relative biological effectiveness than photons. For this reason, an improved treatment of deep-seated tumors is achieved and normal tissue is spared. However, small deviations from the treatment plan can have a large impact on the dose distribution. Therefore, a monitoring is required to assure the quality of the treatment. Particle therapy positron emission tomography (PT-PET) is the only clinically proven method which provides a non-invasive monitoring of dose delivery. It makes use of the β+-activity produced by nuclear fragmentation during irradiation. In order to evaluate these PT-PET measurements, simulations of the β+-activity are necessary. Therefore, it is essential to know the yields of the β+-emitting nuclides at every position of the beam path as exact as possible. We evaluated the three-dimensional Monte-Carlo simulation tool PHITS (version 2.30) [ 1] and the 1D deterministic simulation tool HIBRAC [ 2] with respect to the production of β+-emitting nuclides. The yields of the most important β+-emitting nuclides for carbon, lithium, helium and proton beams have been calculated. The results were then compared with experimental data obtained at GSI Helmholtzzentrum für Schwerionenforschung Darmstadt, Germany. GEANT4 simulations provide an additional benchmark [ 3]. For PHITS, the impact of different nuclear reaction models, total cross-section models and evaporation models on the β+-emitter production has been studied. In general, PHITS underestimates the yields of positron-emitters and cannot compete with GEANT4 so far. The β+-emitters calculated with an extended HIBRAC code were in good agreement with the experimental data for carbon and proton beams and comparable to the GEANT4 results, see [ 4] and Fig. 1. Considering the simulation results and its speed compared with three-dimensional Monte-Carlo tools, HIBRAC is a good candidate for the implementation in clinical routine PT-PET. Fig 1.Depth-dependent yields of the production of 11C and 15O during proton irradiation of a PMMA target with 140 MeV [ 4].

Active photonic lattices: is greater than blackbody intensity possible?

DOE PAGES

Chow, W. W.; Waldmueller, I.

2006-11-10

In this paper, the emission from a radiating source embedded in a photonic lattice is investigated. The photonic lattice spectrum was found to deviate from the blackbody distribution, with intracavity emission suppressed at certain frequencies and significantly enhanced at others. For rapid population relaxation, where the photonic lattice and blackbody populations are described by the same thermal distribution, it was found that the enhancement does not result in output intensities exceeding those of the blackbody. Finally, however, for slow population relaxation, the photonic lattice population has a greater tendency to deviate from thermal equilibrium, resulting in output intensities exceeding thosemore » of the blackbody.« less

Detecting Dark Photons with Reactor Neutrino Experiments

NASA Astrophysics Data System (ADS)

Park, H. K.

2017-08-01

We propose to search for light U (1 ) dark photons, A', produced via kinetically mixing with ordinary photons via the Compton-like process, γ e-→A'e-, in a nuclear reactor and detected by their interactions with the material in the active volumes of reactor neutrino experiments. We derive 95% confidence-level upper limits on ɛ , the A'-γ mixing parameter, ɛ , for dark-photon masses below 1 MeV of ɛ <1.3 ×10-5 and ɛ <2.1 ×10-5, from NEOS and TEXONO experimental data, respectively. This study demonstrates the applicability of nuclear reactors as potential sources of intense fluxes of low-mass dark photons.

Three-color Sagnac source of polarization-entangled photon pairs.

PubMed

Hentschel, Michael; Hübel, Hannes; Poppe, Andreas; Zeilinger, Anton

2009-12-07

We demonstrate a compact and stable source of polarization-entangled pairs of photons, one at 810 nm wavelength for high detection efficiency and the other at 1550 nm for long-distance fiber communication networks. Due to a novel Sagnac-based design of the interferometer no active stabilization is needed. Using only one 30 mm ppKTP bulk crystal the source produces photons with a spectral brightness of 1.13 x 10(6) pairs/s/mW/THz with an entanglement fidelity of 98.2%. Both photons are single-mode fiber coupled and ready to be used in quantum key distribution (QKD) or transmission of photonic quantum states over large distances.

Plasma emission spectroscopy method of tumor therapy

DOEpatents

Fleming, K.J.

1997-03-11

Disclosed are a method and apparatus for performing photon diagnostics using a portable and durable apparatus which incorporates the use of a remote sensing probe in fiberoptic communication with an interferometer or spectrometer. Also disclosed are applications for the apparatus including optically measuring high velocities and analyzing plasma/emission spectral characteristics. 6 figs.

Flexible Transient Optical Waveguides and Surface-Wave Biosensors Constructed from Monocrystalline Silicon.

PubMed

Bai, Wubin; Yang, Hongjun; Ma, Yinji; Chen, Hao; Shin, Jiho; Liu, Yonghao; Yang, Quansan; Kandela, Irawati; Liu, Zhonghe; Kang, Seung-Kyun; Wei, Chen; Haney, Chad R; Brikha, Anlil; Ge, Xiaochen; Feng, Xue; Braun, Paul V; Huang, Yonggang; Zhou, Weidong; Rogers, John A

2018-06-26

Optical technologies offer important capabilities in both biological research and clinical care. Recent interest is in implantable devices that provide intimate optical coupling to biological tissues for a finite time period and then undergo full bioresorption into benign products, thereby serving as temporary implants for diagnosis and/or therapy. The results presented here establish a silicon-based, bioresorbable photonic platform that relies on thin filaments of monocrystalline silicon encapsulated by polymers as flexible, transient optical waveguides for accurate light delivery and sensing at targeted sites in biological systems. Comprehensive studies of the mechanical and optical properties associated with bending and unfurling the waveguides from wafer-scale sources of materials establish general guidelines in fabrication and design. Monitoring biochemical species such as glucose and tracking physiological parameters such as oxygen saturation using near-infrared spectroscopic methods demonstrate modes of utility in biomedicine. These concepts provide versatile capabilities in biomedical diagnosis, therapy, deep-tissue imaging, and surgery, and suggest a broad range of opportunities for silicon photonics in bioresorbable technologies. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quintuple-modality (SERS-MRI-CT-TPL-PTT) plasmonic nanoprobe for theranostics

NASA Astrophysics Data System (ADS)

Liu, Yang; Chang, Zheng; Yuan, Hsiangkuo; Fales, Andrew M.; Vo-Dinh, Tuan

2013-11-01

A unique quintuple-modality theranostic nanoprobe (QMT) is developed with gold nanostars for surface-enhanced Raman scattering (SERS), magnetic resonance imaging (MRI), computed tomography (CT), two-photon luminescence (TPL) imaging and photothermal therapy (PTT). The synthesized gold nanostars were tagged with a SERS reporter and linked with an MRI contrast agent Gd3+. In vitro experiments demonstrated the developed QMT nanoprobe to be a potential theranostic agent for future biomedical applications.A unique quintuple-modality theranostic nanoprobe (QMT) is developed with gold nanostars for surface-enhanced Raman scattering (SERS), magnetic resonance imaging (MRI), computed tomography (CT), two-photon luminescence (TPL) imaging and photothermal therapy (PTT). The synthesized gold nanostars were tagged with a SERS reporter and linked with an MRI contrast agent Gd3+. In vitro experiments demonstrated the developed QMT nanoprobe to be a potential theranostic agent for future biomedical applications. Electronic supplementary information (ESI) available: Details of experimental section, characterization details and relaxivity curve of developed QMT nanoprobe in water at 1.5 T magnetic filed strength. See DOI: 10.1039/c3nr03762b

Determination of the active volumes of solid-state photon-beam dosimetry detectors using the PTB proton microbeam.

PubMed

Poppinga, Daniela; Delfs, Bjoern; Meyners, Jutta; Langner, Frank; Giesen, Ulrich; Harder, Dietrich; Poppe, Bjoern; Looe, Hui K

2018-05-04

This study aims at the experimental determination of the diameters and thicknesses of the active volumes of solid-state photon-beam detectors for clinical dosimetry. The 10 MeV proton microbeam of the PTB (Physikalisch-Technische Bundesanstalt, Braunschweig) was used to examine two synthetic diamond detectors, type microDiamond (PTW Freiburg, Germany), and the silicon detectors Diode E (PTW Freiburg, Germany) and Razor Diode (Iba Dosimetry, Germany). The knowledge of the dimensions of their active volumes is essential for their Monte Carlo simulation and their applications in small-field photon-beam dosimetry. The diameter of the active detector volume was determined from the detector current profile recorded by radially scanning the proton microbeam across the detector. The thickness of the active detector volume was determined from the detector's electrical current, the number of protons incident per time interval and their mean stopping power in the active volume. The mean energy of the protons entering this volume was assessed by comparing the measured and the simulated influence of the thickness of a stack of aluminum preabsorber foils on the detector signal. For all detector types investigated, the diameters measured for the active volume closely agreed with the manufacturers' data. For the silicon Diode E detector, the thickness determined for the active volume agreed with the manufacturer's data, while for the microDiamond detectors and the Razor Diode, the thicknesses measured slightly exceeded those stated by the manufacturers. The PTB microbeam facility was used to analyze the diameters and thicknesses of the active volumes of photon dosimetry detectors for the first time. A new method of determining the thickness values with an uncertainty of ±10% was applied. The results appear useful for further consolidating detailed geometrical knowledge of the solid-state detectors investigated, which are used in clinical small-field photon-beam dosimetry. © 2018 American Association of Physicists in Medicine.

Irradiance optimization of outdoor microalgal cultures using solar tracked photobioreactors.

PubMed

Hindersin, Stefan; Leupold, Marco; Kerner, Martin; Hanelt, Dieter

2013-03-01

Photosynthetic activity and temperature regulation of microalgal cultures (Chlorella vulgaris and Scenedesmus obliquus) under different irradiances controlled by a solar tracker and different cell densities were studied in outdoor flat panel photobioreactors. An automated process control unit regulated light and temperature as well as pH value and nutrient concentration in the culture medium. CO2 was supplied using flue gas from an attached combined block heat and power station. Photosynthetic activity was determined by pulse amplitude modulation fluorometry. Compared to the horizontal irradiance of 55 mol photons m(-2) d(-1) on a clear day, the solar tracked photobioreactors enabled a decrease and increase in the overall light absorption from 19 mol photons m(-2) d(-1) (by rotation out of direct irradiance) to 79 mol photons m(-2) d(-1) (following the position of the sun). At biomass concentrations below 1.1 g cell dry weight (CDW) L(-1), photoinhibition of about 35 % occurred at irradiances of ≥1,000 μmol photons m(-2) s(-1) photosynthetic active radiation (PAR). Using solar tracked photobioreactors, photoinhibition can be reduced and at optimum biomass concentration (≥2.3 g CDW L(-1)), the culture was irradiated up to 2,000 μmol photons m(-2) s(-1) to overcome light limitation with biomass yields of 0.7 g CDW mol photons(-1) and high photosynthetic activities indicated by an effective quantum yield of 0.68 and a maximum quantum yield of 0.80 (F v/F m). Overheating due to high irradiance was avoided by turning the PBR out of the sun or using a cooling system, which maintained the temperature close to the species-specific temperature optima.

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

Chang, Joe Y., E-mail: jychang@mdanderson.org; Jabbour, Salma K.; De Ruysscher, Dirk

Radiation dose escalation has been shown to improve local control and survival in patients with non–small cell lung cancer in some studies, but randomized data have not supported this premise, possibly owing to adverse effects. Because of the physical characteristics of the Bragg peak, proton therapy (PT) delivers minimal exit dose distal to the target volume, resulting in better sparing of normal tissues in comparison to photon-based radiation therapy. This is particularly important for lung cancer given the proximity of the lung, heart, esophagus, major airways, large blood vessels, and spinal cord. However, PT is associated with more uncertainty becausemore » of the finite range of the proton beam and motion for thoracic cancers. PT is more costly than traditional photon therapy but may reduce side effects and toxicity-related hospitalization, which has its own associated cost. The cost of PT is decreasing over time because of reduced prices for the building, machine, maintenance, and overhead, as well as newer, shorter treatment programs. PT is improving rapidly as more research is performed particularly with the implementation of 4-dimensional computed tomography–based motion management and intensity modulated PT. Given these controversies, there is much debate in the oncology community about which patients with lung cancer benefit significantly from PT. The Particle Therapy Co-operative Group (PTCOG) Thoracic Subcommittee task group intends to address the issues of PT indications, advantages and limitations, cost-effectiveness, technology improvement, clinical trials, and future research directions. This consensus report can be used to guide clinical practice and indications for PT, insurance approval, and clinical or translational research directions.« less

A Photosensitizer-Loaded DNA Origami Nanosystem for Photodynamic Therapy.

PubMed

Zhuang, Xiaoxi; Ma, Xiaowei; Xue, Xiangdong; Jiang, Qiao; Song, Linlin; Dai, Luru; Zhang, Chunqiu; Jin, Shubin; Yang, Keni; Ding, Baoquan; Wang, Paul C; Liang, Xing-Jie

2016-03-22

Photodynamic therapy (PDT) offers an alternative for cancer treatment by using ultraviolet or visible light in the presence of a photosensitizer and molecular oxygen, which can produce highly reactive oxygen species that ultimately leading to the ablation of tumor cells by multifactorial mechanisms. However, this technique is limited by the penetration depth of incident light, the hypoxic environment of solid tumors, and the vulnerability of photobleaching reduces the efficiency of many imaging agents. In this work, we reported a cellular level dual-functional imaging and PDT nanosystem BMEPC-loaded DNA origami for photodynamic therapy with high efficiency and stable photoreactive property. The carbazole derivative BMEPC is a one- and two-photon imaging agent and photosensitizer with large two-photon absorption cross section, which can be fully excited by near-infrared light, and is also capable of destroying targets under anaerobic condition by generating reactive intermediates of Type I photodynamic reactions. However, the application of BMEPC was restricted by its poor solubility in aqueous environment and its aggregation caused quenching. We observed BMEPC-loaded DNA origami effectively reduced the photobleaching of BMEPC within cells. Upon binding to DNA origami, the intramolecular rotation of BMEPC became proper restricted, which intensify fluorescence emission and radicals production when being excited. After the BMEPC-loaded DNA origami are taken up by tumor cells, upon irradiation, BMEPC could generate free radicals and be released due to DNA photocleavage as well as the following partially degradation. Apoptosis was then induced by the generation of free radicals. This functional nanosystem provides an insight into the design of photosensitizer-loaded DNA origami for effective intracellular imaging and photodynamic therapy.

Dynamic Photochemical and Optoelectronic Control of Photonic Fano Resonances via Monolayer MoS2 Trions.

PubMed

Zhang, Xingwang; Biekert, Nicolas; Choi, Shinhyuk; Naylor, Carl H; De-Eknamkul, Chawina; Huang, Wenzhuo; Zhang, Xiaojie; Zheng, Xiaorui; Wang, Dake; Johnson, A T Charlie; Cubukcu, Ertugrul

2018-02-14

Active tunability of photonic resonances is of great interest for various applications such as optical switching and modulation based on optoelectronic materials. Manipulation of charged excitons in atomically thin transition metal dichalcogenides (TMDCs) like monolayer MoS 2 offers an unexplored route for diverse functionalities in optoelectronic nanodevices. Here, we experimentally demonstrate the dynamic photochemical and optoelectronic control of the photonic crystal Fano resonances by optical and electrical tuning of monolayer MoS 2 refractive index via trions without any chemical treatment. The strong spatial and spectral overlap between the photonic Fano mode and the active MoS 2 monolayer enables efficient modulation of the Fano resonance. Our approach offers new directions for potential applications in the development of optical modulators based on emerging 2D direct band gap semiconductors.

Fluorinated porphyrinoids as efficient platforms for new photonic materials, sensors, and therapeutics.

PubMed

Bhupathiraju, N V S Dinesh K; Rizvi, Waqar; Batteas, James D; Drain, Charles Michael

2016-01-14

Porphyrinoids are robust heterocyclic dyes studied extensively for their applications in medicine and as photonic materials because of their tunable photophysical properties, diverse means of modifying the periphery, and the ability to chelate most transition metals. Commercial applications include their use as phthalocyanine dyes in optical discs, porphyrins in photodynamic therapy, and as oxygen sensors. Most applications of these dyes require exocyclic moieties to improve solubility, target diseases, modulate photophysical properties, or direct the self-organization into architectures with desired photonic properties. The synthesis of the porphyrinoid depends on the desired application, but the de novo synthesis often involves several steps, is time consuming, and results in low isolated yields. Thus, the application of core porphyrinoid platforms that can be rapidly and efficiently modified to evaluate new molecular architectures allows researchers to focus on the design concepts rather than the synthesis methods, and opens porphyrinoid chemistry to a broader scientific community. We have focused on several widely available, commercially viable porphyrinoids as platforms: meso-perfluorophenylporphyrin, perfluorophthalocyanine, and meso-perfluorophenylcorrole. The perfluorophenylporphyrin is readily converted to the chlorin, bacteriochlorin, and isobacteriochlorin. Derivatives of all six of these core platforms can be efficiently and controllably made via mild nucleophilic aromatic substitution reactions using primary S, N, and O nucleophiles bearing a wide variety of functional groups. The remaining fluoro groups enhance the photo and oxidative stability of the dyes and can serve as spectroscopic signatures to characterize the compounds or in imaging applications using (19)F NMR. This review provides an overview of the chemistry of fluorinated porphyrinoids that are being used as a platform to create libraries of photo-active compounds for applications in medicine and materials.

Near-infrared mediated tumor destruction by photothermal effect of PANI-Np in vivo

NASA Astrophysics Data System (ADS)

Ibarra, L. E.; Yslas, E. I.; Molina, M. A.; Rivarola, C. R.; Romanini, S.; Barbero, C. A.; Rivarola, V. A.; Bertuzzi, M. L.

2013-06-01

Photothermal therapy is a therapy in which photon energy is converted into heat to kill cancer. The purpose of this study is to evaluate the in vivo efficacy of photothermal therapy, toxicity and hepatic and renal function of polyaniline nanoparticles (PANI-Np) in a tumor-bearing mice model. The in vivo efficacy of nanoparticles, following NIR light exposure, was assessed by examining tumor growth over time compared to the untreated control. Signs of drug toxicity and the histopathology and morphology of tumor and tissues, after intratumoral injection treatment, were examined or monitored. Excellent photothermal therapy efficacy is achieved upon intratumoral injection of PANI-Np followed by near-infrared light exposure. These results suggest that PANI-Np could be considered as an effective photothermal agent and pave the way to future cancer therapeutics.

Comparison of organ-at-risk sparing and plan robustness for spot-scanning proton therapy and volumetric modulated arc photon therapy in head-and-neck cancer

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

Barten, Danique L. J., E-mail: d.barten@vumc.nl; Tol, Jim P.; Dahele, Max

Purpose: Proton radiotherapy for head-and-neck cancer (HNC) aims to improve organ-at-risk (OAR) sparing over photon radiotherapy. However, it may be less robust for setup and range uncertainties. The authors investigated OAR sparing and plan robustness for spot-scanning proton planning techniques and compared these with volumetric modulated arc therapy (VMAT) photon plans. Methods: Ten HNC patients were replanned using two arc VMAT (RapidArc) and spot-scanning proton techniques. OARs to be spared included the contra- and ipsilateral parotid and submandibular glands and individual swallowing muscles. Proton plans were made using Multifield Optimization (MFO, using three, five, and seven fields) and Single-field Optimizationmore » (SFO, using three fields). OAR sparing was evaluated using mean dose to composite salivary glands (Comp{sub Sal}) and composite swallowing muscles (Comp{sub Swal}). Plan robustness was determined for setup and range uncertainties (±3 mm for setup, ±3% HU) evaluating V95% and V107% for clinical target volumes. Results: Averaged over all patients Comp{sub Sal}/Comp{sub Swal} mean doses were lower for the three-field MFO plans (14.6/16.4 Gy) compared to the three-field SFO plans (20.0/23.7 Gy) and VMAT plans (23.0/25.3 Gy). Using more than three fields resulted in differences in OAR sparing of less than 1.5 Gy between plans. SFO plans were significantly more robust than MFO plans. VMAT plans were the most robust. Conclusions: MFO plans had improved OAR sparing but were less robust than SFO and VMAT plans, while SFO plans were more robust than MFO plans but resulted in less OAR sparing. Robustness of the MFO plans did not increase with more fields.« less

Femtosecond laser pulse optimization for multiphoton cytometry and control of fluorescence

NASA Astrophysics Data System (ADS)

Tkaczyk, Eric Robert

This body of work encompasses optimization of near infrared femtosecond laser pulses both for enhancement of flow cytometry as well as adaptive pulse shaping to control fluorescence. A two-photon system for in vivo flow cytometry is demonstrated, which allows noninvasive quantification of circulating cell populations in a single live mouse. We monitor fluorescently-labeled red blood cells for more than two weeks, and are also able to noninvasively measure circulation times of two distinct populations of breast cancer cells simultaneously in a single mouse. We build a custom laser excitation source in the form of an extended cavity mode-locked oscillator, which enables superior detection in whole blood or saline of cell lines expressing fluorescent proteins including the green fluorescent protein (GFP), tdTomato and mPlum. A mathematical model explains unique features of the signals. The ability to distinguish different fluorescent species is central to simultaneous measurement of multiple molecular targets in high throughput applications including the multiphoton flow cytometer. We demonstrate that two dyes which are not distinguishable to one-photon measurements can be differentiated and in fact quantified in mixture via phase-shaped two-photon excitation pulses found by a genetic algorithm. We also selectively enhance or suppress two-photon fluorescence of numerous common dyes with tailored pulse shapes. Using a multiplicative (rather than ratiometric) fitness parameter, we are able to control the fluorescence while maintaining a strong signal. With this method, we control the two-photon fluorescence of the blue fluorescent protein (BFP), which is of particular interest in investigations of protein-protein interactions, and has frustrated previous attempts of control. Implementing an acousto-optic interferometer, we use the same experimental setup to measure two-photon excitation cross-sections of dyes and prove that photon-photon interferences are the predominant mechanism of control. This research establishes the basis for molecularly tailored pulse shaping in multiphoton flow cytometry, which will advance our ability to probe the biology of circulating cells during disease progression and response to therapy.

All-photonic quantum repeaters

PubMed Central

Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

2015-01-01

Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

Photonics Applications and Web Engineering: WILGA 2017

NASA Astrophysics Data System (ADS)

Romaniuk, Ryszard S.

2017-08-01

XLth Wilga Summer 2017 Symposium on Photonics Applications and Web Engineering was held on 28 May-4 June 2017. The Symposium gathered over 350 participants, mainly young researchers active in optics, optoelectronics, photonics, modern optics, mechatronics, applied physics, electronics technologies and applications. There were presented around 300 oral and poster papers in a few main topical tracks, which are traditional for Wilga, including: bio-photonics, optical sensory networks, photonics-electronics-mechatronics co-design and integration, large functional system design and maintenance, Internet of Things, measurement systems for astronomy, high energy physics experiments, and other. The paper is a traditional introduction to the 2017 WILGA Summer Symposium Proceedings, and digests some of the Symposium chosen key presentations. This year Symposium was divided to the following topical sessions/conferences: Optics, Optoelectronics and Photonics, Computational and Artificial Intelligence, Biomedical Applications, Astronomical and High Energy Physics Experiments Applications, Material Research and Engineering, and Advanced Photonics and Electronics Applications in Research and Industry.

High-fidelity entanglement swapping and generation of three-qubit GHZ state using asynchronous telecom photon pair sources.

PubMed

Tsujimoto, Yoshiaki; Tanaka, Motoki; Iwasaki, Nobuo; Ikuta, Rikizo; Miki, Shigehito; Yamashita, Taro; Terai, Hirotaka; Yamamoto, Takashi; Koashi, Masato; Imoto, Nobuyuki

2018-01-23

We experimentally demonstrate a high-fidelity entanglement swapping and a generation of the Greenberger-Horne-Zeilinger (GHZ) state using polarization-entangled photon pairs at telecommunication wavelength produced by spontaneous parametric down conversion with continuous-wave pump light. While spatially separated sources asynchronously emit photon pairs, the time-resolved photon detection guarantees the temporal indistinguishability of photons without active timing synchronizations of pump lasers and/or adjustment of optical paths. In the experiment, photons are sufficiently narrowed by fiber-based Bragg gratings with the central wavelengths of 1541 nm & 1580 nm, and detected by superconducting nanowire single-photon detectors with low timing jitters. The observed fidelities of the final states for entanglement swapping and the generated three-qubit state were 0.84 ± 0.04 and 0.70 ± 0.05, respectively.

Radiation dose constraints for organs at risk in neuro-oncology; the European Particle Therapy Network consensus.

PubMed

Lambrecht, Maarten; Eekers, Daniëlle B P; Alapetite, Claire; Burnet, Neil G; Calugaru, Valentin; Coremans, Ida E M; Fossati, Piero; Høyer, Morten; Langendijk, Johannes A; Romero, Alejandra Méndez; Paulsen, Frank; Perpar, Ana; Renard, Laurette; de Ruysscher, Dirk; Timmermann, Beate; Vitek, Pavel; Weber, Damien C; van der Weide, Hiske L; Whitfield, Gillian A; Wiggenraad, Ruud; Roelofs, Erik; Nyström, Petra Witt; Troost, Esther G C

2018-05-17

For unbiased comparison of different radiation modalities and techniques, consensus on delineation of radiation sensitive organs at risk (OARs) and on their dose constraints is warranted. Following the publication of a digital, online atlas for OAR delineation in neuro-oncology by the same group, we assessed the brain OAR-dose constraints in a follow-up study. We performed a comprehensive search to identify the current papers on OAR dose constraints for normofractionated photon and particle therapy in PubMed, Ovid Medline, Cochrane Library, Embase and Web of Science. Moreover, the included articles' reference lists were cross-checked for potential studies that met the inclusion criteria. Consensus was reached among 20 radiation oncology experts in the field of neuro-oncology. For the OARs published in the neuro-oncology literature, we summarized the available literature and recommended dose constraints associated with certain levels of normal tissue complication probability (NTCP) according to the recent ICRU recommendations. For those OARs with lacking or insufficient NTCP data, a proposal for effective and efficient data collection is given. The use of the European Particle Therapy Network-consensus OAR dose constraints summarized in this article is recommended for the model-based approach comparing photon and proton beam irradiation as well as for prospective clinical trials including novel radiation techniques and/or modalities. Copyright © 2018 Elsevier B.V. All rights reserved.

Compton scatter imaging: A promising modality for image guidance in lung stereotactic body radiation therapy

PubMed Central

Redler, Gage; Jones, Kevin C.; Templeton, Alistair; Bernard, Damian; Turian, Julius; Chu, James C. H.

2018-01-01

Purpose Lung stereotactic body radiation therapy (SBRT) requires delivering large radiation doses with millimeter accuracy, making image guidance essential. An approach to forming images of patient anatomy from Compton-scattered photons during lung SBRT is presented. Methods To investigate the potential of scatter imaging, a pinhole collimator and flat-panel detector are used for spatial localization and detection of photons scattered during external beam therapy using lung SBRT treatment conditions (6 MV FFF beam). MCNP Monte Carlo software is used to develop a model to simulate scatter images. This model is validated by comparing experimental and simulated phantom images. Patient scatter images are then simulated from 4DCT data. Results Experimental lung tumor phantom images have sufficient contrast-to-noise to visualize the tumor with as few as 10 MU (0.5 s temporal resolution). The relative signal intensity from objects of different composition as well as lung tumor contrast for simulated phantom images agree quantitatively with experimental images, thus validating the Monte Carlo model. Scatter images are shown to display high contrast between different materials (lung, water, bone). Simulated patient images show superior (~double) tumor contrast compared to MV transmission images. Conclusions Compton scatter imaging is a promising modality for directly imaging patient anatomy during treatment without additional radiation, and it has the potential to complement existing technologies and aid tumor tracking and lung SBRT image guidance. PMID:29360151

Compton scatter imaging: A promising modality for image guidance in lung stereotactic body radiation therapy.

PubMed

Redler, Gage; Jones, Kevin C; Templeton, Alistair; Bernard, Damian; Turian, Julius; Chu, James C H

2018-03-01

Lung stereotactic body radiation therapy (SBRT) requires delivering large radiation doses with millimeter accuracy, making image guidance essential. An approach to forming images of patient anatomy from Compton-scattered photons during lung SBRT is presented. To investigate the potential of scatter imaging, a pinhole collimator and flat-panel detector are used for spatial localization and detection of photons scattered during external beam therapy using lung SBRT treatment conditions (6 MV FFF beam). MCNP Monte Carlo software is used to develop a model to simulate scatter images. This model is validated by comparing experimental and simulated phantom images. Patient scatter images are then simulated from 4DCT data. Experimental lung tumor phantom images have sufficient contrast-to-noise to visualize the tumor with as few as 10 MU (0.5 s temporal resolution). The relative signal intensity from objects of different composition as well as lung tumor contrast for simulated phantom images agree quantitatively with experimental images, thus validating the Monte Carlo model. Scatter images are shown to display high contrast between different materials (lung, water, bone). Simulated patient images show superior (~double) tumor contrast compared to MV transmission images. Compton scatter imaging is a promising modality for directly imaging patient anatomy during treatment without additional radiation, and it has the potential to complement existing technologies and aid tumor tracking and lung SBRT image guidance. © 2018 American Association of Physicists in Medicine.

Quantum State Transfer from a Single Photon to a Distant Quantum-Dot Electron Spin

NASA Astrophysics Data System (ADS)

He, Yu; He, Yu-Ming; Wei, Yu-Jia; Jiang, Xiao; Chen, Kai; Lu, Chao-Yang; Pan, Jian-Wei; Schneider, Christian; Kamp, Martin; Höfling, Sven

2017-08-01

Quantum state transfer from flying photons to stationary matter qubits is an important element in the realization of quantum networks. Self-assembled semiconductor quantum dots provide a promising solid-state platform hosting both single photon and spin, with an inherent light-matter interface. Here, we develop a method to coherently and actively control the single-photon frequency bins in superposition using electro-optic modulators, and measure the spin-photon entanglement with a fidelity of 0.796 ±0.020 . Further, by Greenberger-Horne-Zeilinger-type state projection on the frequency, path, and polarization degrees of freedom of a single photon, we demonstrate quantum state transfer from a single photon to a single electron spin confined in an InGaAs quantum dot, separated by 5 m. The quantum state mapping from the photon's polarization to the electron's spin is demonstrated along three different axes on the Bloch sphere, with an average fidelity of 78.5%.

Shielding implications for secondary neutrons and photons produced within the patient during IMPT.

PubMed

DeMarco, J; Kupelian, P; Santhanam, A; Low, D

2013-07-01

Intensity modulated proton therapy (IMPT) uses a combination of computer controlled spot scanning and spot-weight optimized planning to irradiate the tumor volume uniformly. In contrast to passive scattering systems, secondary neutrons and photons produced from inelastic proton interactions within the patient represent the major source of emitted radiation during IMPT delivery. Various published studies evaluated the shielding considerations for passive scattering systems but did not directly address secondary neutron production from IMPT and the ambient dose equivalent on surrounding occupational and nonoccupational work areas. Thus, the purpose of this study was to utilize Monte Carlo simulations to evaluate the energy and angular distributions of secondary neutrons and photons following inelastic proton interactions within a tissue-equivalent phantom for incident proton spot energies between 70 and 250 MeV. Monte Carlo simulation methods were used to calculate the ambient dose equivalent of secondary neutrons and photons produced from inelastic proton interactions in a tissue-equivalent phantom. The angular distribution of emitted neutrons and photons were scored as a function of incident proton energy throughout a spherical annulus at 1, 2, 3, 4, and 5 m from the phantom center. Appropriate dose equivalent conversion factors were applied to estimate the total ambient dose equivalent from secondary neutrons and photons. A reference distance of 1 m from the center of the patient was used to evaluate the mean energy distribution of secondary neutrons and photons and the resulting ambient dose equivalent. For an incident proton spot energy of 250 MeV, the total ambient dose equivalent (3.6 × 10(-3) mSv per proton Gy) was greatest along the direction of the incident proton spot (0°-10°) with a mean secondary neutron energy of 71.3 MeV. The dose equivalent decreased by a factor of 5 in the backward direction (170°-180°) with a mean energy of 4.4 MeV. An 8 × 8 × 8 cm(3) volumetric spot distribution (5 mm FWHM spot size, 4 mm spot spacing) optimized to produce a uniform dose distribution results in an ambient dose equivalent of 4.5 × 10(-2) mSv per proton Gy in the forward direction. This work evaluated the secondary neutron and photon emission due to monoenergetic proton spots between 70 and 250 MeV, incident on a tissue equivalent phantom. Example calculations were performed to estimate concrete shield thickness based upon appropriate workload and shielding design assumptions. Although lower than traditional passive scattered proton therapy systems, the ambient dose equivalent from secondary neutrons produced by the patient during IMPT can be significant relative to occupational and nonoccupational workers in the vicinity of the treatment vault. This work demonstrates that Monte Carlo simulations are useful as an initial planning tool for studying the impact of the treatment room and maze design on surrounding occupational and nonoccupational work areas.

Combined photon-electron beams in the treatment of the supraclavicular lymph nodes in breast cancer: A novel technique that achieves adequate coverage while reducing lung dose

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

Salem, Ahmed, E-mail: ahmed.salem@doctors.org.uk; Mohamad, Issa; Dayyat, Abdulmajeed

2015-10-01

Radiation pneumonitis is a well-documented side effect of radiation therapy for breast cancer. The purpose of this study was to compare combined photon-electron, photon-only, and electron-only plans in the radiation treatment of the supraclavicular lymph nodes. In total, 13 patients requiring chest wall and supraclavicular nodal irradiation were planned retrospectively using combined photon-electron, photon-only, and electron-only supraclavicular beams. A dose of 50 Gy over 25 fractions was prescribed. Chest wall irradiation parameters were fixed for all plans. The goal of this planning effort was to cover 95% of the supraclavicular clinical target volume (CTV) with 95% of the prescribed dosemore » and to minimize the volume receiving ≥ 105% of the dose. Comparative end points were supraclavicular CTV coverage (volume covered by the 95% isodose line), hotspot volume, maximum radiation dose, contralateral breast dose, mean total lung dose, total lung volume percentage receiving at least 20 Gy (V{sub 20} {sub Gy}), heart volume percentage receiving at least 25 Gy (V{sub 25} {sub Gy}). Electron and photon energies ranged from 8 to 18 MeV and 4 to 6 MV, respectively. The ratio of photon-to-electron fractions in combined beams ranged from 5:20 to 15:10. Supraclavicular nodal coverage was highest in photon-only (mean = 96.2 ± 3.5%) followed closely by combined photon-electron (mean = 94.2 ± 2.5%) and lowest in electron-only plans (mean = 81.7 ± 14.8%, p < 0.001). The volume of tissue receiving ≥ 105% of the prescription dose was higher in the electron-only (mean = 69.7 ± 56.1 cm{sup 3}) as opposed to combined photon-electron (mean = 50.8 ± 40.9 cm{sup 3}) and photon-only beams (mean = 32.2 ± 28.1 cm{sup 3}, p = 0.114). Heart V{sub 25} {sub Gy} was not statistically different among the plans (p = 0.999). Total lung V{sub 20} {sub Gy} was lowest in electron-only (mean = 10.9 ± 2.3%) followed by combined photon-electron (mean = 13.8 ± 2.3%) and highest in photon-only plans (mean = 16.2 ± 3%, p < 0.001). As expected, photon-only plans demonstrated the highest target coverage and total lung V{sub 20} {sub Gy}. The superiority of electron-only beams, in terms of decreasing lung dose, is set back by the dosimetric hotspots associated with such plans. Combined photon-electron treatment is a feasible technique for supraclavicular nodal irradiation and results in adequate target coverage, acceptable dosimetric hotspot volume, and slightly reduced lung dose.« less

Preparation, one- and two-photon properties of carbazole derivatives containing nitrogen heterocyclic ring

NASA Astrophysics Data System (ADS)

Zhang, Yichi; Wang, Ping; Li, Liang; Chen, Zhimin; He, Chunying; Wu, Yiqun

Preparation of recording materials with high two-photon absorption activities is one of the important issues to superhigh- density two-photon absorption (TPA) three-dimensional (3D) optical data storage. In this paper, three new carbazole derivatives containing nitrogen heterocyclic ring with symmetric and asymmetric structures are prepared using ethylene as the π bridge between the carbazole unit and nitrogen heterocyclic ring, namely, 9-butyl-3-(2-(1,8- naphthyridin)vinyl)-carbazole (material 1), 9-butyl-3,6-bis(2-(1,8-naphthyl)vinyl)-carbazole (material 2) and 9-butyl-3,6- bis(2-(quinolin)vinyl)-carbazole (material 3). Their one photon properties including linear absorption spectra, fluorescence emission spectra, and fluorescence quantum yields are studied. The fluorescence excited by 120 fs pulse at 800 nm Ti: sapphire laser operating at 1 kHz repetition rate with different incident powers of 9-butyl-3-(2-(quinolin) vinyl)-carbazole (material 3) was investigated, and two-photon absorption cross-sections has been obtained. It is shown that material 3 containing quinoline rings as electron acceptor with symmetric structure exhibit high two-photon absorption activity. The result implies that material 3 (9-butyl-3-(2-(quinolin) vinyl)-carbazole) is a good candidate as a promising recording material for super-high-density two-photon absorption (TPA) three-dimensional (3D) optical data storage. The influence of chemical structure of the materials on the optical properties is discussed.

High-performance silicon photonics technology for telecommunications applications.

PubMed

Yamada, Koji; Tsuchizawa, Tai; Nishi, Hidetaka; Kou, Rai; Hiraki, Tatsurou; Takeda, Kotaro; Fukuda, Hiroshi; Ishikawa, Yasuhiko; Wada, Kazumi; Yamamoto, Tsuyoshi

2014-04-01

By way of a brief review of Si photonics technology, we show that significant improvements in device performance are necessary for practical telecommunications applications. In order to improve device performance in Si photonics, we have developed a Si-Ge-silica monolithic integration platform, on which compact Si-Ge-based modulators/detectors and silica-based high-performance wavelength filters are monolithically integrated. The platform features low-temperature silica film deposition, which cannot damage Si-Ge-based active devices. Using this platform, we have developed various integrated photonic devices for broadband telecommunications applications.

High-performance silicon photonics technology for telecommunications applications

PubMed Central

Yamada, Koji; Tsuchizawa, Tai; Nishi, Hidetaka; Kou, Rai; Hiraki, Tatsurou; Takeda, Kotaro; Fukuda, Hiroshi; Ishikawa, Yasuhiko; Wada, Kazumi; Yamamoto, Tsuyoshi

2014-01-01

By way of a brief review of Si photonics technology, we show that significant improvements in device performance are necessary for practical telecommunications applications. In order to improve device performance in Si photonics, we have developed a Si-Ge-silica monolithic integration platform, on which compact Si-Ge–based modulators/detectors and silica-based high-performance wavelength filters are monolithically integrated. The platform features low-temperature silica film deposition, which cannot damage Si-Ge–based active devices. Using this platform, we have developed various integrated photonic devices for broadband telecommunications applications. PMID:27877659

Solar Temporal Photon Bunching

NASA Astrophysics Data System (ADS)

Tan, Peng Kian

2018-04-01

Conventional ground-based astronomical observations suffer from image distortion due to atmospheric turbulence. Light from thermal blackbody radiators such as stars exhibits photon bunching behaviour at sufficiently short time-scales which should be independent from atmospherically induced phase fluctuations. However, this photon bunching signal is difficult to observe directly with available detector bandwidths. By performing narrowband spectral filtering on Sunlight and conducting temporal intensity interferometry using actively quenched avalanche photon detectors (APDs), the Solar g(2)(tau) signature was directly measured, consistently throughout the day despite fluctuating weather conditions, cloud cover and elevation angle.

High-performance silicon photonics technology for telecommunications applications

NASA Astrophysics Data System (ADS)

Yamada, Koji; Tsuchizawa, Tai; Nishi, Hidetaka; Kou, Rai; Hiraki, Tatsurou; Takeda, Kotaro; Fukuda, Hiroshi; Ishikawa, Yasuhiko; Wada, Kazumi; Yamamoto, Tsuyoshi

2014-04-01

By way of a brief review of Si photonics technology, we show that significant improvements in device performance are necessary for practical telecommunications applications. In order to improve device performance in Si photonics, we have developed a Si-Ge-silica monolithic integration platform, on which compact Si-Ge-based modulators/detectors and silica-based high-performance wavelength filters are monolithically integrated. The platform features low-temperature silica film deposition, which cannot damage Si-Ge-based active devices. Using this platform, we have developed various integrated photonic devices for broadband telecommunications applications.

Hybrid SPECT-CT and PET-CT imaging of differentiated thyroid carcinoma.

PubMed

Wong, K K; Zarzhevsky, N; Cahill, J M; Frey, K A; Avram, A M

2009-10-01

Hybrid imaging modalities such as radioiodine single photon emission CT with integrated CT ((131)I SPECT-CT) and 2-(fluorine-18)-fluoro-2-deoxy-D-glucose positron emission tomography with integrated CT (FDG PET-CT) allow the rapid and efficient fusion of functional and anatomic images, and provide diagnostic information that may influence management decisions in patients with differentiated thyroid carcinoma (DTC). Diagnostic localisation and therapy of these tumours are dependent upon their capacity to concentrate radioiodine ((131)I) via uptake through the sodium-iodide symporter and retention within the tumour. The prognosis for most patients with DTC is favourable, although controversy exists regarding the role of post-operative (131)I therapy in patients at low-risk for disease. Accurate identification of functional thyroid tissue (benign or malignant) using diagnostic (131)I planar scintigraphy complemented by SPECT-CT imaging enables the completion of post-operative staging and patient risk stratification prior to (131)I therapy administration. In patients with non-iodine-avid tumours (negative (131)I scan but elevated thyroglobulin indicative of persistent or recurrent disease), FDG PET-CT is used to identify tumours with enhanced glucose metabolism and to localise the source of thyroglobulin production. The CT component of this hybrid technology provides anatomic localisation of activity and allows CT-based attenuation correction of PET images. Images from 15 patients illustrate the applications of (131)I SPECT-CT and FDG PET-CT.

Design of photon converter and photoneutron target for High power electron accelerator based BNCT.

PubMed

Rahmani, Faezeh; Seifi, Samaneh; Anbaran, Hossein Tavakoli; Ghasemi, Farshad

2015-12-01

An electron accelerator, ILU-14, with current of 10 mA and 100 kW in power has been considered as one of the options for neutron source in Boron Neutron Capture Therapy (BNCT). The final design of neutron target has been obtained using MCNPX to optimize the neutron production. Tungsten in strip shape and D2O in cylindrical form have been proposed as the photon converter and the photoneutron target, respectively. In addition calculation of heat deposition in the photon target design has been considered to ensure mechanical stability of target. The results show that about 8.37×10(12) photoneutron/s with average energy of 615 keV can be produced by this neutron source design. In addition, using an appropriate beam shaping assembly an epithermal neutron flux of the order of 1.24×10(8) cm(-2) s(-1) can be obtained for BNCT applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Validating dose rate calibration of radiotherapy photon beams through IAEA/WHO postal audit dosimetry service.

PubMed

Jangda, Abdul Qadir; Hussein, Sherali

2012-05-01

In external beam radiation therapy (EBRT), the quality assurance (QA) of the radiation beam is crucial to the accurate delivery of the prescribed dose to the patient. One of the dosimetric parameters that require monitoring is the beam output, specified as the dose rate on the central axis under reference conditions. The aim of this project was to validate dose rate calibration of megavoltage photon beams using the International Atomic Energy Agency (IAEA)/World Health Organisation (WHO) postal audit dosimetry service. Three photon beams were audited: a 6 MV beam from the low-energy linac and 6 and 18 MV beams from a dual high-energy linac. The agreement between our stated doses and the IAEA results was within 1% for the two 6 MV beams and within 2% for the 18 MV beam. The IAEA/WHO postal audit dosimetry service provides an independent verification of dose rate calibration protocol by an international facility.

A mathematical deconvolution formulation for superficial dose distribution measurement by Cerenkov light dosimetry.

PubMed

Brost, Eric Edward; Watanabe, Yoichi

2018-06-01

Cerenkov photons are created by high-energy radiation beams used for radiation therapy. In this study, we developed a Cerenkov light dosimetry technique to obtain a two-dimensional dose distribution in a superficial region of medium from the images of Cerenkov photons by using a deconvolution method. An integral equation was derived to represent the Cerenkov photon image acquired by a camera for a given incident high-energy photon beam by using convolution kernels. Subsequently, an equation relating the planar dose at a depth to a Cerenkov photon image using the well-known relationship between the incident beam fluence and the dose distribution in a medium was obtained. The final equation contained a convolution kernel called the Cerenkov dose scatter function (CDSF). The CDSF function was obtained by deconvolving the Cerenkov scatter function (CSF) with the dose scatter function (DSF). The GAMOS (Geant4-based Architecture for Medicine-Oriented Simulations) Monte Carlo particle simulation software was used to obtain the CSF and DSF. The dose distribution was calculated from the Cerenkov photon intensity data using an iterative deconvolution method with the CDSF. The theoretical formulation was experimentally evaluated by using an optical phantom irradiated by high-energy photon beams. The intensity of the deconvolved Cerenkov photon image showed linear dependence on the dose rate and the photon beam energy. The relative intensity showed a field size dependence similar to the beam output factor. Deconvolved Cerenkov images showed improvement in dose profiles compared with the raw image data. In particular, the deconvolution significantly improved the agreement in the high dose gradient region, such as in the penumbra. Deconvolution with a single iteration was found to provide the most accurate solution of the dose. Two-dimensional dose distributions of the deconvolved Cerenkov images agreed well with the reference distributions for both square fields and a multileaf collimator (MLC) defined, irregularly shaped field. The proposed technique improved the accuracy of the Cerenkov photon dosimetry in the penumbra region. The results of this study showed initial validation of the deconvolution method for beam profile measurements in a homogeneous media. The new formulation accounted for the physical processes of Cerenkov photon transport in the medium more accurately than previously published methods. © 2018 American Association of Physicists in Medicine.

Photonic Crystal Fibers

DTIC Science & Technology

2005-12-01

passive and active versions of each fiber designed under this task. Crystal Fibre shall provide characteristics of the fiber fabricated to include core...passive version of multicore fiber iteration 2. 15. SUBJECT TERMS EOARD, Laser physics, Fibre Lasers, Photonic Crystal, Multicore, Fiber Laser 16...9 00* 0 " CRYSTAL FIBRE INT ODUCTION This report describes the photonic crystal fibers developed under agreement No FA8655-o5-a- 3046. All

Design and characterization of free-running InGaAsP single-photon detector with active-quenching technique

NASA Astrophysics Data System (ADS)

Liu, Junliang; Zhang, Tingfa; Li, Yongfu; Ding, Lei; Tao, Junchao; Wang, Ying; Wang, Qingpu; Fang, Jiaxiong

2017-07-01

A free-running single-photon detector for 1.06 μm wavelength based on an InGaAsP/InP single-photon avalanche diode is presented. The detector incorporates an ultra-fast active-quenching technique to greatly lessen the afterpulsing effects. An improved method for avalanche characterization using electroluminescence is proposed, and the performance of the detector is evaluated. The number of avalanche carriers is as low as 1.68 ×106 , resulting in a low total afterpulse probability of 4% at 233 K, 10% detection efficiency, and 1 μs hold-off time.

Application of epithermal neutron activation in multielement analysis of silicate rocks employing both coaxial Ge(Li) and low energy photon detector systems

USGS Publications Warehouse

Baedecker, P.A.; Rowe, J.J.; Steinnes, E.

1977-01-01

The instrumental activation analysis of silicate rocks using epithermal neutrons has been studied using both high resolution coaxial Ge(Li) detectors and low energy photon detectors, and applied to the determination of 23 elements in eight new U.S.G.S. standard rocks. The analytical use X-ray peaks associated with electron capture or internal conversion processes has been evaluated. Of 28 elements which can be considered to be determinable by instrumental means, the epithermal activation approach is capable of giving improved sensitivity and precision in 16 cases, over the normal INAA procedure. In eleven cases the use of the low energy photon detector is thought to show advantages over convertional coaxial Ge(Li) spectroscopy. ?? 1977 Akade??miai Kiado??.

Detecting Dark Photons with Reactor Neutrino Experiments.

PubMed

Park, H K

2017-08-25

We propose to search for light U(1) dark photons, A^{'}, produced via kinetically mixing with ordinary photons via the Compton-like process, γe^{-}→A^{'}e^{-}, in a nuclear reactor and detected by their interactions with the material in the active volumes of reactor neutrino experiments. We derive 95% confidence-level upper limits on ε, the A^{'}-γ mixing parameter, ε, for dark-photon masses below 1 MeV of ε<1.3×10^{-5} and ε<2.1×10^{-5}, from NEOS and TEXONO experimental data, respectively. This study demonstrates the applicability of nuclear reactors as potential sources of intense fluxes of low-mass dark photons.

System for detecting special nuclear materials

DOEpatents

Jandel, Marian; Rusev, Gencho Yordanov; Taddeucci, Terry Nicholas

2015-07-14

The present disclosure includes a radiological material detector having a convertor material that emits one or more photons in response to a capture of a neutron emitted by a radiological material; a photon detector arranged around the convertor material and that produces an electrical signal in response to a receipt of a photon; and a processor connected to the photon detector, the processor configured to determine the presence of a radiological material in response to a predetermined signature of the electrical signal produced at the photon detector. One or more detectors described herein can be integrated into a detection system that is suited for use in port monitoring, treaty compliance, and radiological material management activities.

Split exponential track length estimator for Monte-Carlo simulations of small-animal radiation therapy

NASA Astrophysics Data System (ADS)

Smekens, F.; Létang, J. M.; Noblet, C.; Chiavassa, S.; Delpon, G.; Freud, N.; Rit, S.; Sarrut, D.

2014-12-01

We propose the split exponential track length estimator (seTLE), a new kerma-based method combining the exponential variant of the TLE and a splitting strategy to speed up Monte Carlo (MC) dose computation for low energy photon beams. The splitting strategy is applied to both the primary and the secondary emitted photons, triggered by either the MC events generator for primaries or the photon interactions generator for secondaries. Split photons are replaced by virtual particles for fast dose calculation using the exponential TLE. Virtual particles are propagated by ray-tracing in voxelized volumes and by conventional MC navigation elsewhere. Hence, the contribution of volumes such as collimators, treatment couch and holding devices can be taken into account in the dose calculation. We evaluated and analysed the seTLE method for two realistic small animal radiotherapy treatment plans. The effect of the kerma approximation, i.e. the complete deactivation of electron transport, was investigated. The efficiency of seTLE against splitting multiplicities was also studied. A benchmark with analog MC and TLE was carried out in terms of dose convergence and efficiency. The results showed that the deactivation of electrons impacts the dose at the water/bone interface in high dose regions. The maximum and mean dose differences normalized to the dose at the isocenter were, respectively of 14% and 2% . Optimal splitting multiplicities were found to be around 300. In all situations, discrepancies in integral dose were below 0.5% and 99.8% of the voxels fulfilled a 1%/0.3 mm gamma index criterion. Efficiency gains of seTLE varied from 3.2 × 105 to 7.7 × 105 compared to analog MC and from 13 to 15 compared to conventional TLE. In conclusion, seTLE provides results similar to the TLE while increasing the efficiency by a factor between 13 and 15, which makes it particularly well-suited to typical small animal radiation therapy applications.

Orthotopic Esophageal Cancers: Intraesophageal Hyperthermia-enhanced Direct Chemotherapy in Rats

PubMed Central

Shi, Yaoping; Zhang, Feng; Bai, Zhibin; Wang, Jianfeng; Qiu, Longhua; Li, Yonggang; Meng, Yanfeng; Valji, Karim

2017-01-01

Purpose To determine the feasibility of using intraesophageal radiofrequency (RF) hyperthermia to enhance local chemotherapy in a rat model with orthotopic esophageal squamous cancers. Materials and Methods The animal protocol was approved by the institutional animal care and use committee and the institutional review board. Human esophageal squamous cancer cells were transduced with luciferase lentiviral particles. Cancer cells, mice with subcutaneous cancer esophageal xenografts, and nude rats with orthotopic esophageal cancers in four study groups of six animals per group were treated with (a) combination therapy of magnetic resonance imaging heating guidewire–mediated RF hyperthermia (42°C) plus local chemotherapy (cisplatin and 5-fluorouracil), (b) chemotherapy alone, (c) RF hyperthermia alone, and (d) phosphate-buffered saline. Bioluminescent optical imaging and transcutaneous ultrasonographic imaging were used to observe bioluminescence signal and changes in tumor size among the groups over 2 weeks, which were correlated with subsequent histologic results. The nonparametric Mann-Whitney U test was used for comparisons of variables. Results Compared with chemotherapy alone, RF hyperthermia alone, and phosphate-buffered saline, combination therapy with RF hyperthermia and chemotherapy induced the lowest cell proliferation (relative absorbance of formazan: 23.4% ± 7, 44.6% ± 7.5, 95.8% ± 2, 100%, respectively; P < .0001), rendered the smallest relative tumor volume (0.65 mm3 ± 0.15, P < .0001) and relative bioluminescence optical imaging photon signal (0.57 × 107 photons per second per square millimeter ± 0.15, P < .001) of mice with esophageal cancer xenografts, as well as the smallest relative tumor volume (0.68 mm3 ± 0.13, P < .05) and relative photon signal (0.56 × 107 photons per second per square millimeter ± 0.11. P < .001) of rat orthotopic esophageal cancers. Conclusion Intraesophageal RF hyperthermia can enhance the effect of chemotherapy on esophageal squamous cell cancers. © RSNA, 2016 PMID:27404050

REVIEW: Optics of globular photonic crystals

NASA Astrophysics Data System (ADS)

Gorelik, V. S.

2007-05-01

The results of experimental and theoretical studies of the optical properties of globular photonic crystals - new physical objects having a crystal structure with the lattice period exceeding considerably the atomic size, are presented. As globular photonic crystals, artificial opal matrices consisting of close-packed silica globules of diameter ~200 nm were used. The reflection spectra of these objects characterising the parameters of photonic bands existing in these crystals in the visible spectral region are presented. The idealised models of the energy band structure of photonic crystals investigated in the review give analytic dispersion dependences for the group velocity and the effective photon mass in a globular photonic crystal. The characteristics of secondary emission excited in globular photonic crystals by monochromatic and broadband radiation are presented. The results of investigations of single-photon-excited delayed scattering of light observed in globular photonic crystals exposed to cw UV radiation and radiation from a repetitively pulsed copper vapour laser are presented. The possibilities of using globular photonic crystals as active media for lasing in different spectral regions are considered. It is proposed to use globular photonic crystals as sensitive sensors in optoelectronic devices for molecular analysis of organic and inorganic materials by the modern methods of laser spectroscopy. The results of experimental studies of spontaneous and stimulated globular scattering of light are discussed. The conditions for observing resonance and two-photon-excited delayed scattering of light are found. The possibility of accumulation and localisation of the laser radiation energy inside a globular photonic crystal is reported.

Accuracy of quantum sensors measuring yield photon flux and photosynthetic photon flux

NASA Technical Reports Server (NTRS)

Barnes, C.; Tibbitts, T.; Sager, J.; Deitzer, G.; Bubenheim, D.; Koerner, G.; Bugbee, B.; Knott, W. M. (Principal Investigator)

1993-01-01

Photosynthesis is fundamentally driven by photon flux rather than energy flux, but not all absorbed photons yield equal amounts of photosynthesis. Thus, two measures of photosynthetically active radiation have emerged: photosynthetic photon flux (PPF), which values all photons from 400 to 700 nm equally, and yield photon flux (YPF), which weights photons in the range from 360 to 760 nm according to plant photosynthetic response. We selected seven common radiation sources and measured YPF and PPF from each source with a spectroradiometer. We then compared these measurements with measurements from three quantum sensors designed to measure YPF, and from six quantum sensors designed to measure PPF. There were few differences among sensors within a group (usually <5%), but YPF values from sensors were consistently lower (3% to 20%) than YPF values calculated from spectroradiometric measurements. Quantum sensor measurements of PPF also were consistently lower than PPF values calculated from spectroradiometric measurements, but the differences were <7% for all sources, except red-light-emitting diodes. The sensors were most accurate for broad-band sources and least accurate for narrow-band sources. According to spectroradiometric measurements, YPF sensors were significantly less accurate (>9% difference) than PPF sensors under metal halide, high-pressure sodium, and low-pressure sodium lamps. Both sensor types were inaccurate (>18% error) under red-light-emitting diodes. Because both YPF and PPF sensors are imperfect integrators, and because spectroradiometers can measure photosynthetically active radiation much more accurately, researchers should consider developing calibration factors from spectroradiometric data for some specific radiation sources to improve the accuracy of integrating sensors.

Few-fJ/bit data transmissions using directly modulated lambda-scale embedded active region photonic-crystal lasers

NASA Astrophysics Data System (ADS)

Takeda, Koji; Sato, Tomonari; Shinya, Akihiko; Nozaki, Kengo; Kobayashi, Wataru; Taniyama, Hideaki; Notomi, Masaya; Hasebe, Koichi; Kakitsuka, Takaaki; Matsuo, Shinji

2013-07-01

A low operating energy is needed for nanocavity lasers designed for on-chip photonic network applications. On-chip nanocavity lasers must be driven by current because they act as light sources driven by electronic circuits. Here, we report the high-speed direct modulation of a lambda-scale embedded active region photonic-crystal (LEAP) laser that holds three records for any type of laser operated at room temperature: a low threshold current of 4.8 µA, a modulation current efficiency of 2.0 GHz µA-0.5 and an operating energy of 4.4 fJ bit-1. Five major technologies make this performance possible: a compact buried heterostructure, a photonic-crystal nanocavity, a lateral p-n junction realized by ion implantation and thermal diffusion, an InAlAs sacrificial layer and current-blocking trenches. We believe that an output power of 2.17 µW and an operating energy of 4.4 fJ bit-1 will enable us to realize on-chip photonic networks in combination with the recently developed highly sensitive receivers.

Photonic network R and D activities in Japan

NASA Astrophysics Data System (ADS)

Kitayama, Ken-ichi; Miki, Tetsuya; Morioka, Toshio; Tsushima, Hideaki; Koga, Masafumi; Mori, Kazuyuki; Araki, Soichiro; Sato, Ken-ichi; Onaka, Hiroshi; Namiki, Shu; Aovama, Tomonori

2005-11-01

R and D activities on photonic networks in Japan are presented. First, milestones in current, ongoing R and D programs supported by Japanese government agencies are introduced, including long-distance and WDM fiber transmission, wavelength routing, optical burst switching, and control plane technology for IP backbone networks. Their goal was set to evolve a legacy telecommunications network to IP over WDM networks by introducing technologies for WDM and wavelength routing. We then discuss the perspectives of so-called PHASE II R and D programs for photonic networks over the next five years until 2010, by focusing on the report which has been recently issued by the Photonic Internet Forum (PIF), a consortium that has major carriers, telecom vendors, and Japanese academics as members. The PHASE II R and D programs should serve to establish a photonic platform to provide abundant bandwidth on demand, at any time on a real-time basis through the customer's initiative, to promote bandwidth-rich applications, such as grid computing, real-time digital-cinema streaming, medical and educational applications, and network storage in e-commerce.

Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy

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

Kabolizadeh, Peyman, E-mail: peyman.kabolizadeh@beaumont.org; Chen, Yen-Lin; Liebsch, Norbert

Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modifiedmore » Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas. Assessment of tumor response to radiation therapy by volumetric analysis is superior to modified RECIST in chordoma patients. Evaluating the soft tissue target volume is an excellent indicator of tumor response.« less

Feasibility of using single photon counting X-ray for lung tumor position estimation based on 4D-CT.

PubMed

Aschenbrenner, Katharina P; Guthier, Christian V; Lyatskaya, Yulia; Boda-Heggemann, Judit; Wenz, Frederik; Hesser, Jürgen W

2017-09-01

In stereotactic body radiation therapy of lung tumors, reliable position estimation of the tumor is necessary in order to minimize normal tissue complication rate. While kV X-ray imaging is frequently used, continuous application during radiotherapy sessions is often not possible due to concerns about the additional dose. Thus, ultra low-dose (ULD) kV X-ray imaging based on a single photon counting detector is suggested. This paper addresses the lower limit of photons to locate the tumor reliably with an accuracy in the range of state-of-the-art methods, i.e. a few millimeters. 18 patient cases with four dimensional CT (4D-CT), which serves as a-priori information, are included in the study. ULD cone beam projections are simulated from the 4D-CTs including Poisson noise. The projections from the breathing phases which correspond to different tumor positions are compared to the ULD projection by means of Poisson log-likelihood (PML) and correlation coefficient (CC), and template matching under these metrics. The results indicate that in full thorax imaging five photons per pixel suffice for a standard deviation in tumor positions of less than half a breathing phase. Around 50 photons per pixel are needed to achieve this accuracy with the field of view restricted to the tumor region. Compared to CC, PML tends to perform better for low photon counts and shifts in patient setup. Template matching only improves the position estimation in high photon counts. The quality of the reconstruction is independent of the projection angle. The accuracy of the proposed ULD single photon counting system is in the range of a few millimeters and therefore comparable to state-of-the-art tumor tracking methods. At the same time, a reduction in photons per pixel by three to four orders of magnitude relative to commercial systems with flatpanel detectors can be achieved. This enables continuous kV image-based position estimation during all fractions since the additional dose to the patient is negligible. Copyright © 2017. Published by Elsevier GmbH.

Study of Dose Perturbation at Bone-Tissue Interfaces in Megavoltage Photon Beam Therapy.

NASA Astrophysics Data System (ADS)

Das, Indra Jeet

Dose perturbations during photon beam irradiation occur at interfaces between two dissimilar media due to the loss of electronic equilibrium. The human body contains many different types of interfaces between soft tissue and other media such as, air cavities, lungs, bones, and high atomic number (Z) materials. The dose to critical organs in the vicinity of high Z interfaces, is what leads to this project. This work describes the dose perturbation at high Z (from bone to lead) interfaces with soft tissue for clinically used megavoltage photon beams in the range of CO-60 gamma rays to 24 MV X-rays. It is divided into three main sections: (1) the dose outside the inhomogeneity in the direction of backscatter, (2) the dose inside the inhomogeneity, and (3) the dose on the photon transmission side of the inhomogeneity. Using different types of parallel plate ion chambers, TLD (powder and chip), and film as dosimeters, the dose perturbation is studied as a function of photon energy, thickness, width, and depth of inhomogeneity, distance from the interface and radiation field size. The concept of Bragg-Gray cavity theory is applied and verified for dose determination inside the inhomogeneity. A significant dose enhancement has been observed on the backscatter side for all photon energies. It is strongly dependent on the atomic number of the inhomogeneity and less dependent on the photon energy, thickness, depth, width, and field size. In the forward direction, a dose reduction occurs at the interface at beam energies lower than 10 MV, whereas a dose enhancement occurs for higher photon energies. The interface effect persists up to a few millimeters on the backscatter side but a distance equivalent to the secondary electron range for the particular photon beams in the forward direction. The dose perturbation is explained on the basis of production and transport of secondary electrons. Empirical functions are derived from the experimental data to predict the dose distribution in the vicinity of an inhomogeneity. These equations could form the basis of a treatment planning system that would accurately represent the dose both at the interface and surrounding tissue.

Lighting the way: photonics leaders II (PL2) optics and photonics teacher professional development

NASA Astrophysics Data System (ADS)

Gilchrist, Pamela O.; Hilliard-Clark, Joyce; Bowles, Tuere; Carpenter, Eric

2014-07-01

A sample group of nineteen teachers completed the second phase of the Photonics Leaders II Optics and Photonics professional development program. Participants took a basic Physics content knowledge test that was designed by a Professor of Physics. The test was completed before the teachers participated in the program and at the end of the program to gather data for statistical inquiry. Statistical studies on pre-test and post-test data indicated significant gains in physics content knowledge over time, and that instructors teaching at the middle school level or only teaching one subject area scored significantly lower during the pretest. Reports from previous participants are summarized to disseminate the percentage of teachers who have incorporated at least one workshop activity and the kind of activity performed. The concerns and limitations reported by previous participants are reviewed as well.

A universal setup for active control of a single-photon detector

NASA Astrophysics Data System (ADS)

Liu, Qin; Lamas-Linares, Antía; Kurtsiefer, Christian; Skaar, Johannes; Makarov, Vadim; Gerhardt, Ilja

2014-01-01

The influence of bright light on a single-photon detector has been described in a number of recent publications. The impact on quantum key distribution (QKD) is important, and several hacking experiments have been tailored to fully control single-photon detectors. Special attention has been given to avoid introducing further errors into a QKD system. We describe the design and technical details of an apparatus which allows to attack a quantum-cryptographic connection. This device is capable of controlling free-space and fiber-based systems and of minimizing unwanted clicks in the system. With different control diagrams, we are able to achieve a different level of control. The control was initially targeted to the systems using BB84 protocol, with polarization encoding and basis switching using beamsplitters, but could be extended to other types of systems. We further outline how to characterize the quality of active control of single-photon detectors.

Integrated Amorphous Silicon p-i-n Temperature Sensor for CMOS Photonics.

PubMed

Rao, Sandro; Pangallo, Giovanni; Della Corte, Francesco Giuseppe

2016-01-06

Hydrogenated amorphous silicon (a-Si:H) shows interesting optoelectronic and technological properties that make it suitable for the fabrication of passive and active micro-photonic devices, compatible moreover with standard microelectronic devices on a microchip. A temperature sensor based on a hydrogenated amorphous silicon p-i-n diode integrated in an optical waveguide for silicon photonics applications is presented here. The linear dependence of the voltage drop across the forward-biased diode on temperature, in a range from 30 °C up to 170 °C, has been used for thermal sensing. A high sensitivity of 11.9 mV/°C in the bias current range of 34-40 nA has been measured. The proposed device is particularly suitable for the continuous temperature monitoring of CMOS-compatible photonic integrated circuits, where the behavior of the on-chip active and passive devices are strongly dependent on their operating temperature.

A universal setup for active control of a single-photon detector

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

Liu, Qin; Skaar, Johannes; Lamas-Linares, Antía

2014-01-15

The influence of bright light on a single-photon detector has been described in a number of recent publications. The impact on quantum key distribution (QKD) is important, and several hacking experiments have been tailored to fully control single-photon detectors. Special attention has been given to avoid introducing further errors into a QKD system. We describe the design and technical details of an apparatus which allows to attack a quantum-cryptographic connection. This device is capable of controlling free-space and fiber-based systems and of minimizing unwanted clicks in the system. With different control diagrams, we are able to achieve a different levelmore » of control. The control was initially targeted to the systems using BB84 protocol, with polarization encoding and basis switching using beamsplitters, but could be extended to other types of systems. We further outline how to characterize the quality of active control of single-photon detectors.« less

Sub-Shot-Noise Transmission Measurement Enabled by Active Feed-Forward of Heralded Single Photons

NASA Astrophysics Data System (ADS)

Sabines-Chesterking, J.; Whittaker, R.; Joshi, S. K.; Birchall, P. M.; Moreau, P. A.; McMillan, A.; Cable, H. V.; O'Brien, J. L.; Rarity, J. G.; Matthews, J. C. F.

2017-07-01

Harnessing the unique properties of quantum mechanics offers the possibility of delivering alternative technologies that can fundamentally outperform their classical counterparts. These technologies deliver advantages only when components operate with performance beyond specific thresholds. For optical quantum metrology, the biggest challenge that impacts on performance thresholds is optical loss. Here, we demonstrate how including an optical delay and an optical switch in a feed-forward configuration with a stable and efficient correlated photon-pair source reduces the detector efficiency required to enable quantum-enhanced sensing down to the detection level of single photons and without postselection. When the switch is active, we observe a factor of improvement in precision of 1.27 for transmission measurement on a per-input-photon basis compared to the performance of a laser emitting an ideal coherent state and measured with the same detection efficiency as our setup. When the switch is inoperative, we observe no quantum advantage.

Photonuclear activation of pure isotopic mediums.

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

Grohman, Mark A.; Lukosi, Eric Daniel

2010-06-01

This work simulated the response of idealized isotopic U-235, U-238, Th-232, and Pu-239 mediums to photonuclear activation with various photon energies. These simulations were conducted using MCNPX version 2.6.0. It was found that photon energies between 14-16 MeV produce the highest response with respect to neutron production rates from all photonuclear reactions. In all cases, Pu-239 responds the highest, followed by U-238. Th-232 produces more overall neutrons at lower photon energies then U-235 when material thickness is above 3.943 centimeters. The time it takes each isotopic material to reach stable neutron production rates in time is directly proportional to themore » material thickness and stopping power of the medium, where thicker mediums take longer to reach stable neutron production rates and thinner media display a neutron production plateau effect, due to the lack of significant attenuation of the activating photons in the isotopic mediums. At this time, no neutron sensor system has time resolutions capable of verifying these simulations, but various indirect methods are possible and should be explored for verification of these results.« less

Implementation and characterization of active feed-forward for deterministic linear optics quantum computing

NASA Astrophysics Data System (ADS)

Böhi, P.; Prevedel, R.; Jennewein, T.; Stefanov, A.; Tiefenbacher, F.; Zeilinger, A.

2007-12-01

In general, quantum computer architectures which are based on the dynamical evolution of quantum states, also require the processing of classical information, obtained by measurements of the actual qubits that make up the computer. This classical processing involves fast, active adaptation of subsequent measurements and real-time error correction (feed-forward), so that quantum gates and algorithms can be executed in a deterministic and hence error-free fashion. This is also true in the linear optical regime, where the quantum information is stored in the polarization state of photons. The adaptation of the photon’s polarization can be achieved in a very fast manner by employing electro-optical modulators, which change the polarization of a trespassing photon upon appliance of a high voltage. In this paper we discuss techniques for implementing fast, active feed-forward at the single photon level and we present their application in the context of photonic quantum computing. This includes the working principles and the characterization of the EOMs as well as a description of the switching logics, both of which allow quantum computation at an unprecedented speed.

Evaluating activation of the shielding walls of a treatment room using the Monte Carlo method

NASA Astrophysics Data System (ADS)

Lee, D.-Y.; Kim, J.-H.

2018-05-01

This study investigates the radiation activation process in a medical linear accelerator, which creates a photon beam with the energy acquired from accelerated electrons. The concrete shielding walls used in conjunction with a medical linear accelerator occupy the largest portion of facility decommissioning costs. Therefore, to evaluate the activation of the shielding wall, this study simulated the operation of a linear accelerator with high-energy photon beams (10, 15, and 20 MV). The results of the simulations showed that the high-energy photon beams produced a large number of neutrons in the areas around the linear accelerator head. Several radionuclides were identified, and their half-lives and radioactivity levels were calculated. Half-lives ranged from 2.62 hours to 3.68E+06 years, and the radioactivity levels of most of the radionuclides were found to satisfy their respective clearance requirements. These results indicate that photon beams of 15 MV or lower satisfy the clearance requirements for decommissioning a linear accelerator facility, whereas those of 20 MV or higher lie partially above the regulatory clearance levels.

Integrated photonics using colloidal quantum dots

NASA Astrophysics Data System (ADS)

Menon, Vinod M.; Husaini, Saima; Okoye, Nicky; Valappil, Nikesh V.

2009-11-01

Integrated photonic devices were realized using colloidal quantum dot composites such as flexible microcavity laser, microdisk emitters and integrated active-passive waveguides. The microcavity laser structure was realized using spin coating and consisted of an all-polymer distributed Bragg reflector with a poly-vinyl carbazole cavity layer embedded with InGaP/ZnS colloidal quantum dots. These microcavities can be peeled off the substrate yielding a flexible structure that can conform to any shape and whose emission spectra can be mechanically tuned. Planar photonic devices consisting of vertically coupled microring resonators, microdisk emitters, active-passive integrated waveguide structures and coupled active microdisk resonators were realized using soft lithography, photo-lithography, and electron beam lithography, respectively. The gain medium in all these devices was a composite consisting of quantum dots embedded in SU8 matrix. Finally, the effect of the host matrix on the optical properties of the quantum dots using results of steady-state and time-resolved luminescence measurements was determined. In addition to their specific functionalities, these novel device demonstrations and their development present a low-cost alternative to the traditional photonic device fabrication techniques.

Osteogenic Sarcoma of the Maxilla: Neutron Therapy for Unresectable Disease

DOE PAGES

Smoron, Geoffrey L.; Lennox, Arlene J.; Mcgee, James L.

1999-01-01

Purpose. To present a case study involving the use of fast neutron therapy to treat an extensive unresectable osteogenic sarcoma arising from the left maxilla. Patient. A 14-year-old male presented with a massive tumor producing severe distortion of his facial structures. He had already received six courses of chemotherapy, which had reduced his pain, but had not measurably reduced the tumor. Methods. The patient was treated with 66 MeV fast neutrons to a dose of 20.4 Gy in 13 fractions over 35 days. Results. CT assessments indicate gradually increasing calcification and noticeable reduction of soft-tissue disease in the frontal sinus,more » orbit and maxillary antrum.There has been some recontouring of the facial structures.The boy conducts an active life, has no pain, and feels well. He was 17 years old at the last follow-up. Discussion. Fast neutrons have a greater biological effectiveness than conventional photon beams. Their use has been associated with improved chance for local control of unresectable disease.This case illustrates their effectiveness in controlling an unusual and aggressive osteogenic sarcoma of the facial bone and sinuses.« less

Changes in cerebral blood flow after cognitive behavior therapy in patients with panic disorder: a SPECT study

PubMed Central

Seo, Ho-Jun; Choi, Young Hee; Chung, Yong-An; Rho, Wangku; Chae, Jeong-Ho

2014-01-01

Aim Inconsistent results continue to be reported in studies that examine the neural correlates of cognitive behavioral therapy (CBT) in patients with panic disorder. We examined the changes in regional cerebral blood flow (rCBF) associated with the alleviation of anxiety by CBT in panic patients. Methods The change in rCBF and clinical symptoms before and after CBT were assessed using single photon emission computed tomography and various clinical measures were analyzed. Results Fourteen subjects who completed CBT showed significant improvements in symptoms on clinical measures, including the Panic and Agoraphobic Scale and the Anxiety Sensitivity Index-Revised. After CBT, increased rCBF was detected in the left postcentral gyrus (BA 43), left precentral gyrus (BA 4), and left inferior frontal gyrus (BA 9 and BA 47), whereas decreased rCBF was detected in the left pons. Correlation analysis of the association between the changes in rCBF and changes in each clinical measure did not show significant results. Conclusion We found changes in the rCBF associated with the successful completion of CBT. The present findings may help clarify the effects of CBT on changes in brain activity in panic disorder. PMID:24790449

Two-Photon Imaging with Diffractive Optical Elements

PubMed Central

Watson, Brendon O.; Nikolenko, Volodymyr; Yuste, Rafael

2009-01-01

Two-photon imaging has become a useful tool for optical monitoring of neural circuits, but it requires high laser power and serial scanning of each pixel in a sample. This results in slow imaging rates, limiting the measurements of fast signals such as neuronal activity. To improve the speed and signal-to-noise ratio of two-photon imaging, we introduce a simple modification of a two-photon microscope, using a diffractive optical element (DOE) which splits the laser beam into several beamlets that can simultaneously scan the sample. We demonstrate the advantages of DOE scanning by enhancing the speed and sensitivity of two-photon calcium imaging of action potentials in neurons from neocortical brain slices. DOE scanning can easily improve the detection of time-varying signals in two-photon and other non-linear microscopic techniques. PMID:19636390

Macroscopic response in active nonlinear photonic crystals.

PubMed

Alagappan, Gandhi; John, Sajeev; Li, Er Ping

2013-09-15

We derive macroscopic equations of motion for the slowly varying electric field amplitude in three-dimensional active nonlinear optical nanostructures. We show that the microscopic Maxwell equations and polarization dynamics can be simplified to a macroscopic one-dimensional problem in the direction of group velocity. For a three-level active material, we derive the steady-state equations for normal mode frequency, threshold pumping, nonlinear Bloch mode amplitude, and lasing in photonic crystals. Our analytical results accurately recapture the results of exact numerical methods.

Photocatalytic Active Radiation Measurements and Use

NASA Technical Reports Server (NTRS)

Davis, Bruce A.; Underwood, Lauren W.

2011-01-01

Photocatalytic materials are being used to purify air, to kill microbes, and to keep surfaces clean. A wide variety of materials are being developed, many of which have different abilities to absorb various wavelengths of light. Material variability, combined with both spectral illumination intensity and spectral distribution variability, will produce a wide range of performance results. The proposed technology estimates photocatalytic active radiation (PcAR), a unit of radiation that normalizes the amount of light based on its spectral distribution and on the ability of the material to absorb that radiation. Photocatalytic reactions depend upon the number of electron-hole pairs generated at the photocatalytic surface. The number of electron-hole pairs produced depends on the number of photons per unit area per second striking the surface that can be absorbed and whose energy exceeds the bandgap of the photocatalytic material. A convenient parameter to describe the number of useful photons is the number of moles of photons striking the surface per unit area per second. The unit of micro-einsteins (or micromoles) of photons per m2 per sec is commonly used for photochemical and photoelectric-like phenomena. This type of parameter is used in photochemistry, such as in the conversion of light energy for photosynthesis. Photosynthetic response correlates with the number of photons rather than by energy because, in this photochemical process, each molecule is activated by the absorption of one photon. In photosynthesis, the number of photons absorbed in the 400 700 nm spectral range is estimated and is referred to as photosynthetic active radiation (PAR). PAR is defined in terms of the photosynthetic photon flux density measured in micro-einsteins of photons per m2 per sec. PcAR is an equivalent, similarly modeled parameter that has been defined for the photocatalytic processes. Two methods to measure the PcAR level are being proposed. In the first method, a calibrated spectrometer with a cosine receptor is used to measure the spectral irradiance. This measurement, in conjunction with the photocatalytic response as a function of wavelength, is used to estimate the PcAR. The photocatalytic response function is determined by measuring photocatalytic reactivity as a function of wavelength. In the second method, simple shaped photocatalytic response functions can be simulated with a broad-band detector with a cosine receptor appropriately filtered to represent the spectral response of the photocatalytic material. This second method can be less expensive than using a calibrated spectrometer.

Hyperbaric Oxygen Therapy Can Diminish Fibromyalgia Syndrome – Prospective Clinical Trial

PubMed Central

Efrati, Shai; Golan, Haim; Bechor, Yair; Faran, Yifat; Daphna-Tekoah, Shir; Sekler, Gal; Fishlev, Gregori; Ablin, Jacob N.; Bergan, Jacob; Volkov, Olga; Friedman, Mony; Ben-Jacob, Eshel; Buskila, Dan

2015-01-01

Background Fibromyalgia Syndrome (FMS) is a persistent and debilitating disorder estimated to impair the quality of life of 2–4% of the population, with 9:1 female-to-male incidence ratio. FMS is an important representative example of central nervous system sensitization and is associated with abnormal brain activity. Key symptoms include chronic widespread pain, allodynia and diffuse tenderness, along with fatigue and sleep disturbance. The syndrome is still elusive and refractory. The goal of this study was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on symptoms and brain activity in FMS. Methods and Findings A prospective, active control, crossover clinical trial. Patients were randomly assigned to treated and crossover groups: The treated group patients were evaluated at baseline and after HBOT. Patients in the crossover-control group were evaluated three times: baseline, after a control period of no treatment, and after HBOT. Evaluations consisted of physical examination, including tender point count and pain threshold, extensive evaluation of quality of life, and single photon emission computed tomography (SPECT) imaging for evaluation of brain activity. The HBOT protocol comprised 40 sessions, 5 days/week, 90 minutes, 100% oxygen at 2ATA. Sixty female patients were included, aged 21–67 years and diagnosed with FMS at least 2 years earlier. HBOT in both groups led to significant amelioration of all FMS symptoms, with significant improvement in life quality. Analysis of SPECT imaging revealed rectification of the abnormal brain activity: decrease of the hyperactivity mainly in the posterior region and elevation of the reduced activity mainly in frontal areas. No improvement in any of the parameters was observed following the control period. Conclusions The study provides evidence that HBOT can improve the symptoms and life quality of FMS patients. Moreover, it shows that HBOT can induce neuroplasticity and significantly rectify abnormal brain activity in pain related areas of FMS patients. Trial Registration ClinicalTrials.gov NCT01827683 PMID:26010952

Active zinc-blende III-nitride photonic structures on silicon

NASA Astrophysics Data System (ADS)

Sergent, Sylvain; Kako, Satoshi; Bürger, Matthias; Blumenthal, Sarah; Iwamoto, Satoshi; As, Donat Josef; Arakawa, Yasuhiko

2016-01-01

We use a layer transfer method to fabricate free-standing photonic structures in a zinc-blende AlN epilayer grown by plasma-assisted molecular beam epitaxy on a 3C-SiC pseudosubstrate and containing GaN quantum dots. The method leads to the successful realization of microdisks, nanobeam photonic crystal cavities, and waveguides integrated on silicon (100) and operating at short wavelengths. We assess the quality of such photonic elements by micro-photoluminescence spectroscopy in the visible and ultraviolet ranges, and extract the absorption coefficient of ZB AlN membranes (α ˜ (2-5) × 102 cm-1).

Magneto-photonic crystal optical sensors with sensitive covers

NASA Astrophysics Data System (ADS)

Dissanayake, Neluka; Levy, Miguel; Chakravarty, A.; Heiden, P. A.; Chen, N.; Fratello, V. J.

2011-08-01

We report on a magneto-photonic crystal on-chip optical sensor for specific analyte detection with polypyrrole and gold nano particles as modified photonic crystal waveguide cover layers. The reaction of the active sensor material with various analytes modifies the electronic structure of the sensor layer causing changes in its refractive index and a strong transduction signal. Magneto-photonic crystal enhanced polarization rotation sensitive to the nature of the cover layer detects the index modification upon analyte adsorption. A high degree of selectivity and sensitivity are observed for aqueous ammonia and methanol with polypyrrole and for thiolated-gold- with gold-nanoparticles covers.

A new water-equivalent 2D plastic scintillation detectors array for the dosimetry of megavoltage energy photon beams in radiation therapy.

PubMed

Guillot, Mathieu; Beaulieu, Luc; Archambault, Louis; Beddar, Sam; Gingras, Luc

2011-12-01

The objective of this work is to present a new 2D plastic scintillation detectors array (2D-PSDA) designed for the dosimetry of megavoltage (MV) energy photon beams in radiation therapy and to characterize its basic performance. We developed a 2D detector array consisting of 781 plastic scintillation detectors (PSDs) inserted into a plane of a water-equivalent phantom. The PSDs were distributed on a 26 × 26 cm(2) grid, with an interdetector spacing of 10 mm, except for two perpendicular lines centered on the detection plane, where the spacing was 5 mm. Each PSD was made of a 1 mm diameter by 3 mm long cylindrical polystyrene scintillating fiber coupled to a clear nonscintillating plastic optical fiber. All of the light signals emitted by the PSDs were read simultaneously with an optical system at a rate of one measurement per second. We characterized the performance of the optical system, the angular dependency of the device, and the perturbation of dose distributions caused by the hundreds of PSDs inserted into the phantom. We also evaluated the capacity of the system to monitor complex multileaf collimator (MLC) sequences such as those encountered in step-and-shoot intensity modulated radiation therapy (IMRT) plans. We compared our results with calculations performed by a treatment planning system and with measurements taken with a 2D ionization chamber array and with a radiochromic film. The detector array that we developed allowed us to measure doses with an average precision of better than 1% for cumulated doses equal to or greater than 6.3 cGy. Our results showed that the dose distributions produced by the 6-MV photon beam are not perturbed (within ±1.1%) by the presence of the hundreds of PSDs located into the phantom. The results also showed that the variations in the beam incidences have little effect on the dose response of the device. For all incidences tested, the passing rates of the gamma tests between the 2D-PSDA and the treatment planning system were higher than 97.5% when the standard clinical tolerances of 3% or 3 mm were used. Excellent agreement was obtained between the doses measured and calculated when we used the 2D-PSDA for monitoring a MLC sequence from a step-and-shoot IMRT plan. We demonstrated the feasibility of using a large number of PSDs in a new 2D-PSDA for the dosimetry of MV energy photon beams in radiation therapy. The excellent precision, accuracy, and low angular dependence of the device indicate that such a prototype could potentially be used as a high-accuracy quality assurance tool for IMRT and arc therapy patient plan verification. The homogeneity and water-equivalence of the prototype we built suggest that this technology could be extended to multiple detection planes by arranging the fibers into more complex orientations, opening the possibility for 3D dosimetry with PSDs.

Basics of particle therapy I: physics

PubMed Central

Park, Seo Hyun

2011-01-01

With the advance of modern radiation therapy technique, radiation dose conformation and dose distribution have improved dramatically. However, the progress does not completely fulfill the goal of cancer treatment such as improved local control or survival. The discordances with the clinical results are from the biophysical nature of photon, which is the main source of radiation therapy in current field, with the lower linear energy transfer to the target. As part of a natural progression, there recently has been a resurgence of interest in particle therapy, specifically using heavy charged particles, because these kinds of radiations serve theoretical advantages in both biological and physical aspects. The Korean government is to set up a heavy charged particle facility in Korea Institute of Radiological & Medical Sciences. This review introduces some of the elementary physics of the various particles for the sake of Korean radiation oncologists' interest. PMID:22984664

Performance characteristics of the EPR dosimetry system with table sugar in radiotherapy applications.

PubMed

Mikou, M; Ghosne, N; El Baydaoui, R; Zirari, Z; Kuntz, F

2015-05-01

Performance characteristics of the megavoltage photon dose measurements with EPR and table sugar were analyzed. An advantage of sugar as a dosimetric material is its tissue equivalency. The minimal detectable dose was found to be 1.5Gy for both the 6 and 18MV photons. The dose response curves are linear up to at least 20Gy. The energy dependence of the dose response in the megavoltage energy range is very weak and probably statistically insignificant. Reproducibility of measurements of various doses in this range performed with the peak-to-peak and double-integral methods is reported. The method can be used in real-time dosimetry in radiation therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characteristics of Bremsstrahlung emissions of (177)Lu, (188)Re, and (90)Y for SPECT/CT quantification in radionuclide therapy.

PubMed

Uribe, Carlos F; Esquinas, Pedro L; Gonzalez, Marjorie; Celler, Anna

2016-05-01

Beta particles emitted by radioisotopes used in targeted radionuclide therapies (TRT) create Bremsstrahlung (BRS) which may affect SPECT quantification when imaging these isotopes. The purpose of the current study was to investigate the characteristics of Bremsstrahlung produced in tissue by three β-emitting radioisotopes used in TRT. Monte Carlo simulations of (177)Lu, (188)Re, and (90)Y sources placed in water filled cylinders were performed. BRS yields, mean energies and energy spectra for (a) all photons generated in the decays, (b) photons that were not absorbed and leave the cylinder, and (c) photons detected by the camera were analyzed. Next, the results of simulations were compared with those from experiments performed on a clinical SPECT camera using same acquisition conditions and phantom configurations as in simulations. Simulations reproduced relatively well the shapes of the measured spectra, except for (90)Y which showed an overestimation in the low energy range. Detailed analysis of the results allowed us to suggest best collimators and imaging conditions for each of the investigated isotopes. Finally, our simulations confirmed that the BRS contribution to the energy spectra in quantitative imaging of (177)Lu and (188)Re could be ignored. For (177)Lu and (188)Re, BRS contributes only marginally to the total spectra recorded by the camera. Our analysis shows that MELP and HE collimators are the best for imaging these two isotopes. For (90)Y, HE collimator should be used. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Two-photon excitation photodynamic therapy with Photofrin

NASA Astrophysics Data System (ADS)

Karotki, Aliaksandr; Khurana, Mamta; Lepock, James R.; Wilson, Brian C.

2005-09-01

Photodynamic therapy (PDT) based on simultaneous two-photon (2-γ) excitation has a potential advantage of highly targeted treatment by means of nonlinear localized photosensitizer excitation. One of the possible applications of 2-γ PDT is a treatment of exodus age-related macular degeneration where highly targeted excitation of photosensitizer in neovasculature is vital for reducing collateral damage to healthy surrounding tissue. To investigate effect of 2-γ PDT Photofrin was used as an archetypal photosensitizer. First, 2-γ absorption properties of Photofrin in the 750 - 900 nm excitation wavelength range were investigated. It was shown that above 800 nm 2-γ interaction was dominant mode of excitation. The 2-γ cross section of Photofrin was rather small and varied between 5 and 10 GM (1 GM = 10-50 cm4s/photon) in this wavelength range. Next, endothelial cells treated with Photofrin were used to model initial effect of 2-γ PDT on neovasculature. Ultrashort laser pulses provided by mode-locked Ti:sapphire laser (pulse duration at the sample 300 fs, repetition rate 90 MHz, mean laser power 10 mW, excitation wavelength 850 nm) were used for the excitation of the photosensitizer. Before 2-γ excitation of the Photofrin cells formed a single continuous sheet at the bottom of the well. The tightly focused laser light was scanned repeatedly over the cell layer. After irradiation the cell layer of the control cells stayed intact while cells treated with photofrin became clearly disrupted. The light doses required were high (6300 Jcm(-2) for ~ 50% killing), but 2-γ cytotoxicity was unequivocally demonstrated.

A Theoretical Approach to Selection of a Biologically Active Substance in Ultra-Low Doses for Effective Action on a Biological System.

PubMed

Boldyreva, Liudmila Borisovna

2018-05-01

 An approach is offered to selecting a biologically active substance (BAS) in ultra-low dose for effective action on a biological system (BS). The technique is based on the assumption that BAS in ultra-low doses exerts action on BS by means of spin supercurrent emerging between the spin structure created by BAS, on the one hand, and the spin structure created by BS, on the other hand. According to modern quantum-mechanical concepts, these spin structures may be virtual particles pairs having precessing spin (that is, be essentially spin vortices in the physical vacuum) and created by the quantum entities that BAS and BS consist of. The action is effective provided there is equality of precession frequencies of spins in these spin structures.  In this work, some methods are considered for determining the precession frequencies of spins in virtual particles pairs: (1) determination of energy levels of quantum entities that BS and BAS consist of; (2) the use of spin-flip effect of the virtual particles pair spin, the effect being initiated by action of magnetic vector potential (the spin-flip effect takes place when the varied frequency of the magnetic vector potential equals the precession frequency of the spin); (3) determining the frequencies of photons effectively acting on BS.  It is shown that the effect of BAS in ultra-low doses on BS can be replaced by the effect of a beam of low-intensity photons, if the frequency of photons equals the precession frequency of spin in spin structures created by BS. Consequently, the color of bodies placed near a biological system is able to exert an effective action on the biological system: that is "color therapy" is possible. It is also supposed that the spin-flip effect may be used not only for determining the precession frequency of spin in spin structures created by BS but also for therapeutic action on biological systems. The Faculty of Homeopathy.

Neutron therapy in Saudi Arabia: an overview and results of dose searching study in head and neck cancer.

PubMed

el-Akkad, S; Schultz, H P; Ahmad, K; Clubb, B; McArthur, P; Dobson, H; DeVol, E

1992-01-01

The King Faisal Specialist Hospital and Research Centre is the only center in the Middle East that incorporates a neutron therapy facility. The neutron beam is produced by a cyclotron, which produces a beam by either a (d(15)+Be) or (p(26)+Be) reaction. The beam from the proton reaction is selected for therapy because of its superior physical characteristics. These were verified by an intercomparison conducted by the European Organization for Research on Treatment of Cancer (EORTC) Heavy Particle Therapy Group. Full beam data are presented. The first study in the neutron therapy Program is on the treatment of squamous cancers of the head and neck. This consists of two parts. Part I is a dose searching phase and Part II is a comparison of our current photon treatment versus neutrons using the neutron dose selected by Part I of the study. Results of the dose searching phase (Part I) are presented.

De novo development of a cerebral arteriovenous malformation following radiation therapy: Case report and an update to classical arteriovenous malformation nomenclature.

PubMed

Koch, Matthew J; Agarwalla, Pankaj K; Stapleton, Christopher J; Ogilvy, Christopher S; Loeffler, Jay S

2016-06-01

Cerebral arteriovenous malformations (AVM) are traditionally considered primary congenital lesions that result from embryological aberrations in vasculogenesis. Recent insights, however, suggest that these lesions may be secondary to a vascular insult such as ischemia or trauma. Herein, the authors present a rare case of a secondary cerebral AVM, occurring in a young girl who received prior cranial radiation therapy. At age 3years, she underwent surgical resection, chemotherapy, and photon radiation therapy for treatment of a fourth ventricular ependymoma. At age 19years, she developed new onset seizures and was found to have a left medial temporal lobe AVM. Her seizures were managed successfully with anti-epileptic medications and the AVM was treated with proton radiation therapy. This case highlights a rare but possible vascular sequela of radiation therapy and adds to the growing body of evidence that cerebral AVM may arise as secondary lesions. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Exceptional enhancement of Raman scattering on silver chlorobromide nanocube photonic crystals: chemical and photonic contributions

DOE PAGES

Li, Zheng; Gosztola, David J.; Sun, Cheng-Jun; ...

2015-02-02

Photonic crystals made from self-assembly of mono-dispersed AgCl xBr 1-x nanocubes, which are not plasmonically active, have been discovered to exceptionally enhance Raman scattering of molecules chemically adsorbed on their surfaces. Comprehensive control measurements and X-ray absorption near-edge structure spectroscopy indicate that the Raman enhancement on the AgCl xBr 1-x nanocube photonic crystals is primarily ascribed to the chemical enhancement mechanism associated with the chemical interactions between adsorbing molecules and the AgCl xBr 1-x surfaces. In addition, the ordering of the AgCl xBr 1-x nanocubes in the photonic crystals can selectively reflect Raman scattering back to the detector at themore » bandgap position of the photonic crystals to provide additional enhancement, i.e., photonic mode enhancement. The thiophenol molecules adsorbed on the AgCl 0.44Br 0.56 nanocube photonic crystals exhibit astonishingly strong Raman signals that are on the same order of magnitude as those recorded from the thiophenol molecules adsorbed on the assembled Ag nanocubes.« less

Laser camp: shining a light on optics careers

NASA Astrophysics Data System (ADS)

Donnelly, Judith; Goyette, Donna; Magnani, Nancy; Wosczyna-Birch, Karen

2008-08-01

Three Rivers Community College offers two associate degree programs in optics/photonics, and graduates have their choice of jobs in New England and across the United States. Nonetheless, students, their parents, teachers and guidance counselors are largely unaware of the career opportunities in the photonics industry. To promote optics/photonics career awareness, we hosted two versions of "Laser Camp" in 2007 and 2008. Hands-on activities were chosen to promote awareness of optical science and technology careers and to provide "take home" information and souvenirs to share with family and friends. In this paper, we discuss the logistics of funding, marketing, permissions, transportation and food service and share our student-tested activities.

Embeded photonic crystal at the interface of p-GaN and Ag reflector to improve light extraction of GaN-based flip-chip light-emitting diode

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

Zhen, Aigong; Ma, Ping, E-mail: maping@semi.ac.cn; Zhang, Yonghui

2014-12-22

In this experiment, a flip-chip light-emitting diode with photonic crystal was fabricated at the interface of p-GaN and Ag reflector via nanospheres lithography technique. In this structure, photonic crystal could couple with the guide-light efficiently by reason of the little distance between photonic crystal and active region. The light output power of light emitting diode with embedded photonic crystal was 1.42 times larger than that of planar flip-chip light-emitting diode. Moreover, the embedded photonic crystal structure makes the far-field divergence angle decreased by 18° without spectra shift. The three-dimensional finite difference time domain simulation results show that photonic crystal couldmore » improve the light extraction, and enhance the light absorption caused by Ag reflector simultaneously, because of the roughed surface. The depth of photonic crystal is the key parameter affecting the light extraction and absorption. Light extraction efficiency increases with the depth photonic crystal structure rapidly, and reaches the maximum at the depth 80 nm, beyond which light extraction decrease drastically.« less

Temporal Lobe Reactions After Carbon Ion Radiation Therapy: Comparison of Relative Biological Effectiveness–Weighted Tolerance Doses Predicted by Local Effect Models I and IV

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

Gillmann, Clarissa, E-mail: clarissa.gillmann@med.uni-heidelberg.de; Jäkel, Oliver; Heidelberg Ion Beam Therapy Center

2014-04-01

Purpose: To compare the relative biological effectiveness (RBE)–weighted tolerance doses for temporal lobe reactions after carbon ion radiation therapy using 2 different versions of the local effect model (LEM I vs LEM IV) for the same patient collective under identical conditions. Methods and Materials: In a previous study, 59 patients were investigated, of whom 10 experienced temporal lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base chordoma and chondrosarcoma at Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast enhancements on T1-weighted MRI images within a median follow-up time ofmore » 2.5 years. Although the derived RBE-weighted temporal lobe doses were based on the clinically applied LEM I, we have now recalculated the RBE-weighted dose distributions using LEM IV and derived dose-response curves with Dmax,V-1 cm³ (the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding the volume of 1 cm³ with the highest dose) as an independent dosimetric variable. The resulting RBE-weighted tolerance doses were compared with those of the previous study to assess the clinical impact of LEM IV relative to LEM I. Results: The dose-response curve of LEM IV is shifted toward higher values compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication probability (TD{sub 5}) increases from 68.8 ± 3.3 to 78.3 ± 4.3 Gy (RBE) for LEM IV as compared to LEM I. Conclusions: LEM IV predicts a clinically significant increase of the RBE-weighted tolerance doses for the temporal lobe as compared to the currently applied LEM I. The limited available photon data do not allow a final conclusion as to whether RBE predictions of LEM I or LEM IV better fit better clinical experience in photon therapy. The decision about a future clinical application of LEM IV therefore requires additional analysis of temporal lobe reactions in a comparable photon-treated collective using the same dosimetric variable as in the present study.« less

Improving the neutron-to-photon discrimination capability of detectors used for neutron dosimetry in high energy photon beam radiotherapy.

PubMed

Irazola, L; Terrón, J A; Bedogni, R; Pola, A; Lorenzoli, M; Sánchez-Nieto, B; Gómez, F; Sánchez-Doblado, F

2016-09-01

The increasing interest of the medical community to radioinduced second malignancies due to photoneutrons in patients undergoing high-energy radiotherapy, has stimulated in recent years the study of peripheral doses, including the development of some dedicated active detectors. Although these devices are designed to respond to neutrons only, their parasitic photon response is usually not identically zero and anisotropic. The impact of these facts on measurement accuracy can be important, especially in points close to the photon field-edge. A simple method to estimate the photon contribution to detector readings is to cover it with a thermal neutron absorber with reduced secondary photon emission, such as a borated rubber. This technique was applied to the TNRD (Thermal Neutron Rate Detector), recently validated for thermal neutron measurements in high-energy photon radiotherapy. The positive results, together with the accessibility of the method, encourage its application to other detectors and different clinical scenarios. Copyright © 2016 Elsevier Ltd. All rights reserved.

A 64-pixel NbTiN superconducting nanowire single-photon detector array for spatially resolved photon detection.

PubMed

Miki, Shigehito; Yamashita, Taro; Wang, Zhen; Terai, Hirotaka

2014-04-07

We present the characterization of two-dimensionally arranged 64-pixel NbTiN superconducting nanowire single-photon detector (SSPD) array for spatially resolved photon detection. NbTiN films deposited on thermally oxidized Si substrates enabled the high-yield production of high-quality SSPD pixels, and all 64 SSPD pixels showed uniform superconducting characteristics within the small range of 7.19-7.23 K of superconducting transition temperature and 15.8-17.8 μA of superconducting switching current. Furthermore, all of the pixels showed single-photon sensitivity, and 60 of the 64 pixels showed a pulse generation probability higher than 90% after photon absorption. As a result of light irradiation from the single-mode optical fiber at different distances between the fiber tip and the active area, the variations of system detection efficiency (SDE) in each pixel showed reasonable Gaussian distribution to represent the spatial distributions of photon flux intensity.

Plasmonic Enhancement in BiVO4 Photonic Crystals for Efficient Water Splitting

PubMed Central

Zhang, Liwu; Lin, Chia-Yu; Valev, Ventsislav K; Reisner, Erwin; Steiner, Ullrich; Baumberg, Jeremy J

2014-01-01

Photo-electrochemical water splitting is a very promising and environmentally friendly route for the conversion of solar energy into hydrogen. However, the solar-to-H2 conversion efficiency is still very low due to rapid bulk recombination of charge carriers. Here, a photonic nano-architecture is developed to improve charge carrier generation and separation by manipulating and confining light absorption in a visible-light-active photoanode constructed from BiVO4 photonic crystal and plasmonic nanostructures. Synergistic effects of photonic crystal stop bands and plasmonic absorption are observed to operate in this photonic nanostructure. Within the scaffold of an inverse opal photonic crystal, the surface plasmon resonance is significantly enhanced by the photonic Bragg resonance. Nanophotonic photoanodes show AM 1.5 photocurrent densities of 3.1 ± 0.1 mA cm−2 at 1.23 V versus RHE, which is among the highest for oxide-based photoanodes and over 4 times higher than the unstructured planar photoanode. PMID:24916174

Plasmonic enhancement in BiVO4 photonic crystals for efficient water splitting.

PubMed

Zhang, Liwu; Lin, Chia-Yu; Valev, Ventsislav K; Reisner, Erwin; Steiner, Ullrich; Baumberg, Jeremy J

2014-10-15

Photo-electrochemical water splitting is a very promising and environmentally friendly route for the conversion of solar energy into hydrogen. However, the solar-to-H2 conversion efficiency is still very low due to rapid bulk recombination of charge carriers. Here, a photonic nano-architecture is developed to improve charge carrier generation and separation by manipulating and confining light absorption in a visible-light-active photoanode constructed from BiVO4 photonic crystal and plasmonic nanostructures. Synergistic effects of photonic crystal stop bands and plasmonic absorption are observed to operate in this photonic nanostructure. Within the scaffold of an inverse opal photonic crystal, the surface plasmon resonance is significantly enhanced by the photonic Bragg resonance. Nanophotonic photoanodes show AM 1.5 photocurrent densities of 3.1 ± 0.1 mA cm(-2) at 1.23 V versus RHE, which is among the highest for oxide-based photoanodes and over 4 times higher than the unstructured planar photoanode. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ABOUT the phenomenon produced by the successive jumps of the peripheric electrons, at the absorbtion of the intense photon beam by the metal

NASA Astrophysics Data System (ADS)

Isarie, Claudiu I.; Oprean, Constantin; Marginean, Ion; Nemes, Toderita; Isarie, Ilie V.; Bokor, Corina; Itu, Sorin

2011-03-01

When a photon beam is in impact with a metal, the peripheric electrons which belong to the bombarded material are made jumps, and in the same time, new photons are absorbed by electrons which had not time to come back to the fundamental levels. At a high level concentration of the radiant energy, a peripheral electron, could sequentially absorb more photons and could realize energetic jumps in succesive phase, equivalent with some photons of high energy which have wave-lenght smaller than the incidental photons. After some succesive photon absorbtion of the same electron, in the interval in which it is not activated by new photons, the electron comes back to the fundamental level and delivers the accumulated energy, in photons of higher energy, which have a lower energy than the incident beam. Comming back to the fundamental level, the electrons disturb the electronic cloud of the atom or ion they belong. After a huge number of such phenomenon the electronic cloud which is succesivelly disturbed, produces an oscillation which risez the temperature of the nucleus. The authors have studied the conditions which generated the rise of temperature and multiple radiations at the place where the photons bombard the metal.

Technologic developments in the field of photonics for the detection of urinary bladder cancer.

PubMed

Palmer, Scott; Sokolovski, Sergei G; Rafailov, Edik; Nabi, Ghulam

2013-12-01

Bladder cancer is a common cause of morbidity and mortality worldwide in an aging population. Each year, thousands of people, mostly men, are diagnosed with this disease, but many of them present too late to receive optimal treatment. As with all cancers, early diagnosis of bladder cancer significantly improves the efficacy of therapy and increases survival and recurrence-free survival rates. Ongoing research has identified many limitations about the sensitivity of standard diagnostic procedures in detecting early-stage tumors and precancerous changes. The consequences of this are often tumor progression and increased tumor burden, leading to a decrease in patient quality of life and a vast increase in treatment costs. The necessity for improved early detection of bladder cancer has spurred on research into novel methods that use a wide range of biological and photonic phenomena. This review will broadly discuss standard detection methodologies and their major limitations before covering novel photonic techniques for early tumor detection and staging, assessing their diagnostic accuracy for flat and precancerous changes. We will do so in the context of both cystoscopic examination and the screening of voided urine and will also touch on the concept of using photonic technology as a surgical tool for tumor ablation. Copyright © 2013 Elsevier Inc. All rights reserved.

Incidental Testicular Irradiation From Prostate IMRT: It All Adds Up

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

King, Christopher R., E-mail: crking@stanford.ed; Maxim, Peter G.; Hsu, Annie

Purpose: To identify the technical aspects of image-guided intensity-modulated radiation therapy (IMRT) for localized prostate cancer that could result in a clinically meaningful incidental dose to the testes. Methods and Materials: We examined three sources that contribute incidental dose to the testes, namely, from internal photon scattering from IMRT small field and large pelvic nodal fields with 6 or 15 MV, from neutrons when >10-MV photons are used, and from daily image-guided fiducial-based portal imaging. Using clinical data from 10 patients who received IMRT for prostate cancer, and thermo-luminescent dosimeter measurements in phantom, we estimated the dose to the testesmore » from each of these sources. Results: A mean testicular dose of 172 and 220 cGy results from internal photon scatter for pelvic nodal fields and 68 and 93 cGy for prostate-only fields, for 6- and 15-MV energies, respectively. For 15-MV photon energies, the mean testicular dose from neutrons is 60 cGy for pelvic fields and 31 cGy for prostate-only fields. From daily portal MV image guidance, the testes-in-field mean dose is 350 cGy, whereas the testes-out-of-field scatter dose is 16 cGy. Dosimetric comparisons between IMRT using 6-MV and 15-MV photon energies are not significantly different. Worst-case scenarios can potentially deliver cumulative incidental mean testicular doses of 630 cGy, whereas best-case scenarios can deliver only 84 cGy. Conclusions: Incidental dose to the testes from prostate IMRT can be minimized by opting to restrict the use of elective pelvic nodal fields, by choosing photon energies <10 MV, and by using the smallest port sizes necessary for daily image guidance.« 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.