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1.
Nutrition ; 78: 110857, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32599415

RESUMO

OBJECTIVES: Maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) are mucosal α-glucosidases required for the digestion of starch to glucose. We hypothesized that a dietary approach to reduce Mgam and Si activities can reduce glucose generation and absorption, and improve glucose control. METHODS: Rice starch was entrapped in alginate microspheres to moderate in vitro digestion properties. Three groups of 8-wk old mice (n = 8) were conditioned for 7 d with low 13C-starch-based materials differing in digestion rates (fast, slow, and slower), and then given a digestible 13C-labeled cornstarch test feeding to determine its digestion to glucose. RESULTS: Conditioning of the small intestine with the slowly digestible starches for 7 d reduced jejunal α-glucosidase and sucrase activities, as well as glucose absorption for the slowly digestible starch slower group (P < 0.01). A correlative relationship was found between glucose absorption from a cornstarch test feeding given at d 7 and jejunal α-glucosidase and sucrase activities (R2 = 0.64; 0.67). However, total prandial glucose levels during the 2-h feeding period did not differ. CONCLUSIONS: Decreased glucogenesis from a digestible starch feeding was found in mice conditioned on slowly digestible starch diets, suggesting that a dietary approach incorporating slowly digestible starches may change α-glucosidase activities to moderate glucose absorption rate.

2.
Int J Radiat Oncol Biol Phys ; 106(2): 440-448, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31928642

RESUMO

PURPOSE: Recent studies suggest that ultrahigh-dose-rate, "FLASH," electron radiation therapy (RT) decreases normal tissue damage while maintaining tumor response compared with conventional dose rate RT. Here, we describe a novel RT apparatus that delivers FLASH proton RT (PRT) using double scattered protons with computed tomography guidance and provide the first report of proton FLASH RT-mediated normal tissue radioprotection. METHODS AND MATERIALS: Absolute dose was measured at multiple depths in solid water and validated against an absolute integral charge measurement using a Faraday cup. Real-time dose rate was obtained using a NaI detector to measure prompt gamma rays. The effect of FLASH versus standard dose rate PRT on tumors and normal tissues was measured using pancreatic flank tumors (MH641905) derived from the KPC autochthonous PanCa model in syngeneic C57BL/6J mice with analysis of fibrosis and stem cell repopulation in small intestine after abdominal irradiation. RESULTS: The double scattering and collimation apparatus was dosimetrically validated with dose rates of 78 ± 9 Gy per second and 0.9 ± 0.08 Gy per second for the FLASH and standard PRT. Whole abdominal FLASH PRT at 15 Gy significantly reduced the loss of proliferating cells in intestinal crypts compared with standard PRT. Studies with local intestinal irradiation at 18 Gy revealed a reduction to near baseline levels of intestinal fibrosis for FLASH-PRT compared with standard PRT. Despite this difference, FLASH-PRT did not demonstrate tumor radioprotection in MH641905 pancreatic cancer flank tumors after 12 or 18 Gy irradiation. CONCLUSIONS: We have designed and dosimetrically validated a FLASH-PRT system with accurate control of beam flux on a millisecond time scale and online monitoring of the integral and dose delivery time structure. Using this system, we found that FLASH-PRT decreases acute cell loss and late fibrosis after whole-abdomen and focal intestinal RT, whereas tumor growth inhibition is preserved between the 2 modalities.


Assuntos
Órgãos em Risco/efeitos da radiação , Terapia com Prótons/instrumentação , Lesões Experimentais por Radiação/prevenção & controle , Proteção Radiológica/instrumentação , Radioterapia Guiada por Imagem/instrumentação , Abdome/efeitos da radiação , Animais , Proliferação de Células/efeitos da radiação , Desenho de Equipamento/métodos , Estudos de Viabilidade , Feminino , Fibrose , Raios gama , Intestino Delgado/patologia , Intestino Delgado/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Tratamentos com Preservação do Órgão/instrumentação , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/patologia , Neoplasias Pancreáticas/radioterapia , Terapia com Prótons/métodos , Proteção Radiológica/métodos , Radiometria/métodos , Radioterapia Guiada por Imagem/métodos , Espalhamento de Radiação , Células-Tronco/efeitos da radiação , Tomografia Computadorizada por Raios X
3.
Br J Radiol ; 93(1107): 20190879, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31804145

RESUMO

OBJECTIVE: Locally recurrent disease is of increasing concern in (non-)small cell lung cancer [(N)SCLC] patients. Local reirradiation with photons or particles may be of benefit to these patients. In this multicentre in silico trial performed within the Radiation Oncology Collaborative Comparison (ROCOCO) consortium, the doses to the target volumes and organs at risk (OARs) were compared when using several photon and proton techniques in patients with recurrent localised lung cancer scheduled to undergo reirradiation. METHODS: 24 consecutive patients with a second primary (N)SCLC or recurrent disease after curative-intent, standard fractionated radio(chemo)therapy were included in this study. The target volumes and OARs were centrally contoured and distributed to the participating ROCOCO sites. Remaining doses to the OARs were calculated on an individual patient's basis. Treatment planning was performed by the participating site using the clinical treatment planning system and associated beam characteristics. RESULTS: Treatment plans for all modalities (five photon and two proton plans per patient) were available for 22 patients (N = 154 plans). 3D-conformal photon therapy and double-scattered proton therapy delivered significantly lower doses to the target volumes. The highly conformal techniques, i.e., intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), CyberKnife, TomoTherapy and intensity-modulated proton therapy (IMPT), reached the highest doses in the target volumes. Of these, IMPT was able to statistically significantly decrease the radiation doses to the OARs. CONCLUSION: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. They, however, significantly differ in the dose deposited in the OARs. The therapeutic options, i.e., reirradiation or systemic therapy, need to be carefully weighed and discussed with the patients. ADVANCES IN KNOWLEDGE: Highly conformal photon and proton beam techniques enable high-dose reirradiation of the target volume. In light of the abilities of the various highly conformal techniques to spare specific OARs, the therapeutic options need to be carefully weighed and patients included in the decision-making process.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Recidiva Local de Neoplasia/radioterapia , Órgãos em Risco/efeitos da radiação , Fótons/uso terapêutico , Terapia com Prótons/métodos , Reirradiação/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Conjuntos de Dados como Assunto , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Órgãos em Risco/diagnóstico por imagem , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/métodos , Resultado do Tratamento
5.
Med Phys ; 45(7): e707-e721, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29679491

RESUMO

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 the clinical implementation of these techniques are discussed.


Assuntos
Acústica , Diagnóstico por Imagem/métodos , Terapia com Prótons/métodos , Humanos , Processamento de Imagem Assistida por Computador , Aceleradores de Partículas , Terapia com Prótons/instrumentação , Radiometria
6.
Blood Adv ; 2(7): 754-761, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29599195

RESUMO

Thrombocytopenia is a significant complication of chemotherapy and radiation therapy. Platelet factor 4 (PF4; CXCL4) is a negative paracrine of megakaryopoiesis. We have shown that PF4 levels are inversely related to steady-state platelet counts, and to the duration and severity of chemotherapy- and radiation-induced thrombocytopenia (CIT and RIT, respectively). Murine studies suggest that blocking the effect of PF4 improves megakaryopoiesis, raising nadir platelet counts and shortening the time to platelet count recovery. We examined the ability of 2-O, 3-O desulfated heparin (ODSH), a heparin variant with little anticoagulant effects, to neutralize PF4's effects on megakaryopoiesis. Using megakaryocyte colony assays and liquid cultures, we show that ODSH restored megakaryocyte proliferation in PF4-treated Cxcl4-/- murine and human CD34+-derived megakaryocyte cultures (17.4% megakaryocyte colonies, P < .01 compared with PF4). In murine CIT and RIT models, ODSH, started 24 hours after injury, was examined for the effect on hematopoietic recovery demonstrating higher platelet count nadirs (9% ± 5% treated vs 4% ± 4% control) and significantly improved survival in treated animals (73% treated vs 36% control survival). Treatment with ODSH was able to reduce intramedullary free PF4 concentrations by immunohistochemical analysis. In summary, ODSH mitigated CIT and RIT in mice by neutralizing the intramedullary negative paracrine PF4. ODSH, already in clinical trials in humans as an adjuvant to chemotherapy, may be an important, clinically relevant therapeutic for CIT and RIT.


Assuntos
Heparina/análogos & derivados , Trombocitopenia/tratamento farmacológico , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Heparina/farmacologia , Heparina/uso terapêutico , Humanos , Megacariócitos/citologia , Camundongos , Contagem de Plaquetas , Fator Plaquetário 4/sangue , Fator Plaquetário 4/efeitos dos fármacos , Fator Plaquetário 4/farmacologia , Trombocitopenia/induzido quimicamente , Trombocitopenia/etiologia , Trombopoese
7.
Radiother Oncol ; 128(1): 139-146, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29545019

RESUMO

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


Assuntos
Carbono/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Radioterapia com Íons Pesados/métodos , Neoplasias Pulmonares/radioterapia , Fótons/uso terapêutico , Terapia com Prótons/métodos , Carcinoma Pulmonar de Células não Pequenas/patologia , Relação Dose-Resposta à Radiação , Humanos , Neoplasias Pulmonares/patologia , Mediastino/efeitos da radiação , Órgãos em Risco/efeitos da radiação , Radiocirurgia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos
8.
Phys Med Biol ; 63(2): 025018, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29176057

RESUMO

Acoustic-based proton range verification (protoacoustics) is a potential in vivo technique for determining the Bragg peak position. Previous measurements and simulations have been restricted to homogeneous water tanks. Here, a CT-based simulation method is proposed and applied to a liver and prostate case to model the effects of tissue heterogeneity on the protoacoustic amplitude and time-of-flight range verification accuracy. For the liver case, posterior irradiation with a single proton pencil beam was simulated for detectors placed on the skin. In the prostate case, a transrectal probe measured the protoacoustic pressure generated by irradiation with five separate anterior proton beams. After calculating the proton beam dose deposition, each CT voxel's material properties were mapped based on Hounsfield Unit values, and thermoacoustically-generated acoustic wave propagation was simulated with the k-Wave MATLAB toolbox. By comparing the simulation results for the original liver CT to homogenized variants, the effects of heterogeneity were assessed. For the liver case, 1.4 cGy of dose at the Bragg peak generated 50 mPa of pressure (13 cm distal), a 2× lower amplitude than simulated in a homogeneous water tank. Protoacoustic triangulation of the Bragg peak based on multiple detector measurements resulted in 0.4 mm accuracy for a δ-function proton pulse irradiation of the liver. For the prostate case, higher amplitudes are simulated (92-1004 mPa) for closer detectors (<8 cm). For four of the prostate beams, the protoacoustic range triangulation was accurate to ⩽1.6 mm (δ-function proton pulse). Based on the results, application of protoacoustic range verification to heterogeneous tissue will result in decreased signal amplitudes relative to homogeneous water tank measurements, but accurate range verification is still expected to be possible.


Assuntos
Acústica , Simulação por Computador , Neoplasias Hepáticas/radioterapia , Imagens de Fantasmas , Neoplasias da Próstata/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Método de Monte Carlo , Neoplasias da Próstata/diagnóstico por imagem , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X/métodos
9.
Phys Med Biol ; 63(2): 025036, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29160776

RESUMO

Clinical proton beam quality assurance (QA) requires a simple and accurate method to measure the proton beam Bragg peak (BP) depth. Protoacoustics, the measurement of the pressure waves emitted by thermal expansion resulting from proton dose deposition, may be used to obtain the depth of the BP in a phantom by measuring the time-of-flight of the pressure wave. Rectangular and cylindrical phantoms of different materials (aluminum, lead, and polyethylene) were used for protoacoustic studies. Four different methods for analyzing the protoacoustic signals are compared. Data analysis shows that, for Methods 1 and 2, plastic phantoms have better accuracy than metallic ones because of the lower speed of sound. Method 3 does not require characterizing the speed of sound in the material, but it results in the largest error. Method 4 exhibits minimal error, less than 3 mm (with an uncertainty ⩽1.5 mm) for all the materials and geometries. Psuedospectral wave-equation simulations (k-Wave MATLAB toolbox) are used to understand the origin of acoustic reflections within the phantom. The presented simulations and experiments show that protoacoustic measurements may provide a low cost and simple QA procedure for proton beam range verification as long as the proper phantoms and calculation methods are used.


Assuntos
Acústica , Imagens de Fantasmas , Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Dosagem Radioterapêutica , Razão Sinal-Ruído
10.
Int J Radiat Oncol Biol Phys ; 99(1): 210-218, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28816148

RESUMO

PURPOSE: To report the first clinical results and value assessment of prompt gamma imaging for in vivo proton range verification in pencil beam scanning mode. METHODS AND MATERIALS: A stand-alone, trolley-mounted, prototype prompt gamma camera utilizing a knife-edge slit collimator design was used to record the prompt gamma signal emitted along the proton tracks during delivery of proton therapy for a brain cancer patient. The recorded prompt gamma depth detection profiles of individual pencil beam spots were compared with the expected profiles simulated from the treatment plan. RESULTS: In 6 treatment fractions recorded over 3 weeks, the mean (± standard deviation) range shifts aggregated over all spots in 9 energy layers were -0.8 ± 1.3 mm for the lateral field, 1.7 ± 0.7 mm for the right-superior-oblique field, and -0.4 ± 0.9 mm for the vertex field. CONCLUSIONS: This study demonstrates the feasibility and illustrates the distinctive benefits of prompt gamma imaging in pencil beam scanning treatment mode. Accuracy in range verification was found in this first clinical case to be better than the range uncertainty margin applied in the treatment plan. These first results lay the foundation for additional work toward tighter integration of the system for in vivo proton range verification and quantification of range uncertainties.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Câmaras gama , Terapia com Prótons/métodos , Cintilografia/métodos , Fracionamento da Dose de Radiação , Desenho de Equipamento , Estudos de Viabilidade , Humanos , Cintilografia/instrumentação , Planejamento da Radioterapia Assistida por Computador
11.
J Pediatr Gastroenterol Nutr ; 65(2): e35-e42, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28267073

RESUMO

BACKGROUND AND OBJECTIVE: Although named because of its sucrose hydrolytic activity, this mucosal enzyme plays a leading role in starch digestion because of its maltase and glucoamylase activities. Sucrase-deficient mutant shrews, Suncus murinus, were used as a model to investigate starch digestion in patients with congenital sucrase-isomaltase deficiency.Starch digestion is much more complex than sucrose digestion. Six enzyme activities, 2 α-amylases (Amy), and 4 mucosal α-glucosidases (maltases), including maltase-glucoamylase (Mgam) and sucrase-isomaltase (Si) subunit activities, are needed to digest starch to absorbable free glucose. Amy breaks down insoluble starch to soluble dextrins; mucosal Mgam and Si can either directly digest starch to glucose or convert the post-α-amylolytic dextrins to glucose. Starch digestion is reduced because of sucrase deficiency and oral glucoamylase enzyme supplement can correct the starch maldigestion. The aim of the present study was to measure glucogenesis in suc/suc shrews after feeding of starch and improvement of glucogenesis by oral glucoamylase supplements. METHODS: Sucrase mutant (suc/suc) and heterozygous (+/suc) shrews were fed with C-enriched starch diets. Glucogenesis derived from starch was measured as blood C-glucose enrichment and oral recombinant C-terminal Mgam glucoamylase (M20) was supplemented to improve starch digestion. RESULTS: After feedings, suc/suc and +/suc shrews had different starch digestions as shown by blood glucose enrichment and the suc/suc had lower total glucose concentrations. Oral supplements of glucoamylase increased suc/suc total blood glucose and quantitative starch digestion to glucose. CONCLUSIONS: Sucrase deficiency, in this model of congenital sucrase-isomaltase deficiency, reduces blood glucose response to starch feeding. Supplementing the diet with oral recombinant glucoamylase significantly improved starch digestion in the sucrase-deficient shrew.


Assuntos
Erros Inatos do Metabolismo dos Carboidratos/tratamento farmacológico , Suplementos Nutricionais , Digestão/fisiologia , Fármacos Gastrointestinais/uso terapêutico , Glucana 1,4-alfa-Glucosidase/uso terapêutico , Amido/metabolismo , Complexo Sacarase-Isomaltase/deficiência , Sacarase/deficiência , Administração Oral , Animais , Animais Geneticamente Modificados , Biomarcadores/metabolismo , Glicemia/metabolismo , Erros Inatos do Metabolismo dos Carboidratos/metabolismo , Masculino , Distribuição Aleatória , Musaranhos , Complexo Sacarase-Isomaltase/metabolismo , Resultado do Tratamento
12.
Phys Med Biol ; 61(24): 8945-8946, 2016 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-27910821

RESUMO

A reply is provided to the points raised in the comment by Dr Sitek (2016 Phys. Med. Biol. 61 8941) on Polf et al (2015 Phys. Med. Biol. 60 7085).


Assuntos
Raios gama , Terapia com Prótons/métodos , Cintilografia/instrumentação , Estudos de Viabilidade , Humanos
13.
Med Phys ; 43(9): 5213, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27587053

RESUMO

PURPOSE: Measurement of the arrival times of thermoacoustic waves induced by pulsed proton dose depositions (protoacoustics) may provide a proton range verification method. The goal of this study is to characterize the required dose and protoacoustic proton range (distance) verification accuracy in a homogeneous water medium at a hospital-based clinical cyclotron. METHODS: Gaussian-like proton pulses with 17 µs widths and instantaneous currents of 480 nA (5.6 × 10(7) protons/pulse, 3.4 cGy/pulse at the Bragg peak) were generated by modulating the cyclotron proton source with a function generator. After energy degradation, the 190 MeV proton pulses irradiated a water phantom, and the generated protoacoustic emissions were measured by a hydrophone. The detector position and proton pulse characteristics were varied. The experimental results were compared to simulations. Different arrival time metrics derived from acoustic waveforms were compared, and the accuracy of protoacoustic time-of-flight distance calculations was assessed. RESULTS: A 27 mPa noise level was observed in the treatment room during irradiation. At 5 cm from the proton beam, an average maximum pressure of 5.2 mPa/1 × 10(7) protons (6.1 mGy at the Bragg peak) was measured after irradiation with a proton pulse with 10%-90% rise time of 11 µs. Simulation and experiment arrival times agreed well, and the observed 2.4 µs delay between simulation and experiment is attributed to the difference between the hydrophone's acoustic and geometric centers. Based on protoacoustic arrival times, the beam axis position was measured to within (x, y) = (-2.0, 0.5) ± 1 mm. After deconvolution of the exciting proton pulse, the protoacoustic compression peak provided the most consistent measure of the distance to the Bragg peak, with an error distribution with mean = - 4.5 mm and standard deviation = 2.0 mm. CONCLUSIONS: Based on water tank measurements at a clinical hospital-based cyclotron, protoacoustics is a potential method for measuring the beam's position (x and y within 2.0 mm) and Bragg peak range (2.0 mm standard deviation), although range verification will require simulation or experimental calibration to remove systematic error. Based on extrapolation, a protoacoustic arrival time reproducibility of 1.5 µs (2.2 mm) is achievable with 2 Gy of total deposited dose. Of the compared methods, deconvolution of the excitation proton pulse is the best technique for extracting protoacoustic arrival times, particularly if there is variation in the proton pulse shape.


Assuntos
Acústica , Prótons , Água , Temperatura , Fatores de Tempo
15.
Phys Med Biol ; 61(6): 2213-42, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26913839

RESUMO

The unique dose deposition of proton beams generates a distinctive thermoacoustic (protoacoustic) signal, which can be used to calculate the proton range. To identify the expected protoacoustic amplitude, frequency, and arrival time for different proton pulse characteristics encountered at hospital-based proton sources, the protoacoustic pressure emissions generated by 150 MeV, pencil-beam proton pulses were simulated in a homogeneous water medium. Proton pulses with Gaussian widths ranging up to 200 µs were considered. The protoacoustic amplitude, frequency, and time-of-flight (TOF) range accuracy were assessed. For TOF calculations, the acoustic pulse arrival time was determined based on multiple features of the wave. Based on the simulations, Gaussian proton pulses can be categorized as Dirac-delta-function-like (FWHM < 4 µs) and longer. For the δ-function-like irradiation, the protoacoustic spectrum peaks at 44.5 kHz and the systematic error in determining the Bragg peak range is <2.6 mm. For longer proton pulses, the spectrum shifts to lower frequencies, and the range calculation systematic error increases (⩽ 23 mm for FWHM of 56 µs). By mapping the protoacoustic peak arrival time to range with simulations, the residual error can be reduced. Using a proton pulse with FWHM = 2 µs results in a maximum signal-to-noise ratio per total dose. Simulations predict that a 300 nA, 150 MeV, FWHM = 4 µs Gaussian proton pulse (8.0 × 10(6) protons, 3.1 cGy dose at the Bragg peak) will generate a 146 mPa pressure wave at 5 cm beyond the Bragg peak. There is an angle dependent systematic error in the protoacoustic TOF range calculations. Placing detectors along the proton beam axis and beyond the Bragg peak minimizes this error. For clinical proton beams, protoacoustic detectors should be sensitive to <400 kHz (for -20 dB). Hospital-based synchrocyclotrons and cyclotrons are promising sources of proton pulses for generating clinically measurable protoacoustic emissions.


Assuntos
Acústica , Terapia com Prótons/métodos , Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Ciclotrons , Humanos , Terapia com Prótons/instrumentação , Dosagem Radioterapêutica , Razão Sinal-Ruído
16.
Med Phys ; 42(12): 7090-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26632062

RESUMO

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


Assuntos
Ciclotrons , Terapia com Prótons/instrumentação , Som , Hospitais , Pressão , Água
18.
Phys Med Biol ; 60(18): 7085-99, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-26317610

RESUMO

The purpose of this paper is to evaluate the ability of a prototype Compton camera (CC) to measure prompt gamma rays (PG) emitted during delivery of clinical proton pencil beams for prompt gamma imaging (PGI) as a means of providing in vivo verification of the delivered proton radiotherapy beams. A water phantom was irradiated with clinical 114 MeV and 150 MeV proton pencil beams. Up to 500 cGy of dose was delivered per irradiation using clinical beam currents. The prototype CC was placed 15 cm from the beam central axis and PGs from 0.2 MeV up to 6.5 MeV were measured during irradiation. From the measured data (2D) images of the PG emission were reconstructed. (1D) profiles were extracted from the PG images and compared to measured depth dose curves of the delivered proton pencil beams. The CC was able to measure PG emission during delivery of both 114 MeV and 150 MeV proton beams at clinical beam currents. 2D images of the PG emission were reconstructed for single 150 MeV proton pencil beams as well as for a 5 × 5 cm mono-energetic layer of 114 MeV pencil beams. Shifts in the Bragg peak (BP) range were detectable on the 2D images. 1D profiles extracted from the PG images show that the distal falloff of the PG emission profile lined up well with the distal BP falloff. Shifts as small as 3 mm in the beam range could be detected from the 1D PG profiles with an accuracy of 1.5 mm or better. However, with the current CC prototype, a dose of 400 cGy was required to acquire adequate PG signal for 2D PG image reconstruction. It was possible to measure PG interactions with our prototype CC during delivery of proton pencil beams at clinical dose rates. Images of the PG emission could be reconstructed and shifts in the BP range were detectable. Therefore PGI with a CC for in vivo range verification during proton treatment delivery is feasible. However, improvements in the prototype CC detection efficiency and reconstruction algorithms are necessary to make it a clinically viable PGI system.


Assuntos
Diagnóstico por Imagem/instrumentação , Raios gama , Processamento de Imagem Assistida por Computador/métodos , Imagens de Fantasmas , Terapia com Prótons/instrumentação , Terapia com Prótons/métodos , Água/química , Algoritmos , Estudos de Viabilidade , Humanos , Método de Monte Carlo
19.
Acta Oncol ; 53(10): 1312-20, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24797885

RESUMO

BACKGROUND: Adjuvant chemoradiotherapy improves both overall- and relapse-free survival in patients with resected gastric cancer. However, this comes at the cost of increased treatment-related toxicity. Proton therapy (PT) has distinct dosimetric characteristics that may reduce dose to normal tissues, improving the therapeutic ratio. The purpose of this treatment planning study is to compare PT and intensity-modulated x-ray therapy (IMXT) in gastric cancer with regards to normal tissue sparing. MATERIAL AND METHODS: The patient population consisted of resected gastric cancer patients treated at a single institution between 2008 and 2013. Patients who had undergone 4D CT simulation were replanned to the originally delivered doses (45-54 Gy in 25-30 daily fractions) using six-field photon IMXT and 2-3-field PT (double scattering-uniform scanning techniques). RESULTS: Thirteen patients were eligible for the planning comparison. IMXT provided slightly higher homogeneity indices (median values 0.04 ± 0.01 vs. 0.07 ± 0.01, p = 0.03). PT resulted in significantly (p < 0.05) lower intermediate-low doses for all the normal tissues examined (small bowel V15 82 ml vs. 133 ml, liver mean doses Gy 11.9 vs. 14.4 Gy, left/right kidney mean doses 5/0.9 Gy vs. 7.8/3.1 Gy, heart mean doses 7.4 Gy vs. 9.5 Gy). The total energy deposited outside the target volume was significantly lower with PT (median integral dose 90.1 J vs. 129 J). Four patients were treated with PT: treatment was feasible and verifications scans showed that target coverage was robust. CONCLUSION: PT can contribute to normal tissue sparing in the adjuvant treatment of gastric cancer, with a potential benefit in terms of compliance to treatment, acute and late toxicities.


Assuntos
Órgãos em Risco/efeitos da radiação , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias Gástricas/radioterapia , Estudos de Viabilidade , Humanos , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/diagnóstico por imagem , Lesões por Radiação/prevenção & controle , Radiografia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
20.
Phys Med Biol ; 59(9): 2325-40, 2014 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-24732052

RESUMO

Recent studies have suggested that the characteristics of prompt gammas (PGs) emitted from excited nuclei during proton therapy are advantageous for determining beam range during treatment delivery. Since PGs are only emitted while the beam is on, the feasibility of using PGs for online treatment verification depends greatly on the design of highly efficient detectors. The purpose of this work is to characterize how PG detection changes as a function of distance from the patient as a means of guiding the design and usage of clinical PG imaging detectors. Using a Monte Carlo model (GEANT4.9.4) we studied the detection rate (PGs per incident proton) of a high purity germanium detector for both the total PG emission and the characteristic 6.13 MeV PG emission from (16)O emitted during proton irradiation. The PG detection rate was calculated as a function of distance from the isocenter of the proton treatment nozzle for: (1) a water phantom irradiated with a proton pencil beam and (2) a prostate patient irradiated with a scanning beam proton therapy treatment field (lateral field size: ∼6 cm × 6 cm, beam range: 23.5 cm). An analytical expression of the PG detection rate as a function of distance from isocenter, detector size, and proton beam energy was then developed. The detection rates were found to be 1.3 × 10(-6) for oxygen and 3.9 × 10(-4) for the total PG emission, respectively, with the detector placed 11 cm from isocenter for a 40 MeV pencil beam irradiating a water phantom. The total PG detection rate increased by ∼85 ± 3% for beam energies greater than 150 MeV. The detection rate was found to be approximately 2.1 × 10(-6) and 1.7 × 10(-3) for oxygen and total PG emission, respectively, during delivery of a single pencil beam during a scanning beam treatment for prostate cancer. The PG detection rate as a function of distance from isocenter during irradiation of a water phantom with a single proton pencil beam was described well by the model of a point source irradiating a cylindrical detector of a known diameter over the range of beam energies commonly used for proton therapy. For the patient studies, it was necessary to divide the point source equation by an exponential factor in order to correctly predict the falloff of the PG detection rate as a function of distance from isocenter.


Assuntos
Raios gama/uso terapêutico , Terapia com Prótons/métodos , Humanos , Masculino , Método de Monte Carlo , Imagens de Fantasmas , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Terapia com Prótons/instrumentação , Tomografia Computadorizada por Raios X , Água
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