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1.
Pract Radiat Oncol ; 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35777728

##### RESUMO

PURPOSE: Cherenkov imaging is now clinically available as a radiotherapy treatment verification tool. The aim of this work was to discover the benefits of always-on Cherenkov imaging as a novel incident detection and quality improvement system through review of all imaging in our center. METHODS: Multi-camera Cherenkov imaging systems were permanently installed in three treatment bunkers, imaging continuously over a year. Images were acquired as part of normal treatment procedure and reviewed for potential treatment delivery anomalies. RESULTS: In total, 622 unique patients were evaluated for this study. We identified nine patients with treatment anomalies occurring over their course of treatment, which were only detected via Cherenkov imaging. Categorizing each event indicated issues arising in simulation, planning, pre-treatment review, and treatment delivery, and none of the incidents were detected before this review by conventional measures. The incidents identified in this study included dose to unintended areas in planning, dose to unintended areas due to positioning at treatment, and non-ideal bolus placement during setup. CONCLUSIONS: Cherenkov imaging was shown to provide a unique method of detecting radiotherapy incidents that would have otherwise gone undetected. While none of the events detected in this study reached the threshold of reporting, they identified opportunities for practice improvement and demonstrated added value of Cherenkov Imaging in QA programs.

2.
Br J Radiol ; : 20211346, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35834415

##### RESUMO

OBJECTIVES: Examine the responses of multiple image similarity metrics to detect patient positioning errors in radiotherapy observed through Cherenkov imaging, which may be used to optimize automated incident detection. METHODS: An anthropomorphic phantom mimicking patient vasculature, a biological marker seen in Cherenkov images, was simulated for a breast radiotherapy treatment. The phantom was systematically shifted in each translational direction, and Cherenkov images were captured during treatment delivery at each step. The responses of mutual information (MI) and the Î³ passing rate (%GP) were compared to that of existing field-shape matching image metrics, the Dice coefficient, and mean distance to conformity (MDC). Patient images containing other incidents were analyzed to verify the best detection algorithm for different incident types. RESULTS: Positional shifts in all directions were registered by both MI and %GP, degrading monotonically as the shifts increased. Shifts in intensity, which may result from erythema or bolus-tissue air gaps, were detected most by %GP. However, neither metric detected beam-shape misalignment, such as that caused by dose to unintended areas, as well as currently employed metrics (Dice and MDC). CONCLUSIONS: This study indicates that different radiotherapy incidents may be detected by comparing both inter- and intrafractional Cherenkov images with a corresponding image similarity metric, varying with the type of incident. Future work will involve determining appropriate thresholds per metric for automatic flagging. ADVANCES IN KNOWLEDGE: Classifying different algorithms for the detection of various radiotherapy incidents allows for the development of an automatic flagging system, eliminating the burden of manual review of Cherenkov images.

3.
Phys Med Biol ; 67(9)2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35313290

##### RESUMO

Objective.Existing ultra-high dose rate (UHDR) electron sources lack dose rate independent dosimeters and a calibrated dose control system for accurate delivery. In this study, we aim to develop a custom single-pulse dose monitoring and a real-time dose-based control system for a FLASH enabled clinical linear accelerator (Linac).Approach.A commercially available point scintillator detector was coupled to a gated integrating amplifier and a real-time controller for dose monitoring and feedback control loop. The controller was programmed to integrate dose for each radiation pulse and stop the radiation beam when the prescribed dose was delivered. Additionally, the scintillator was mounted in a solid water phantom and placed underneath mice skin forin vivodose monitoring. The scintillator was characterized in terms of its radiation stability, mean dose-rate (Dm), and dose per pulse (Dp) dependence.Main results.TheDpexhibited a consistent ramp-up period across â¼4-5 pulse. The plastic scintillator was shown to be linear withDm(40-380 Gy s-1) andDp(0.3-1.3 Gy Pulse-1) to within +/- 3%. However, the plastic scintillator was subject to significant radiation damage (16%/kGy) for the initial 1 kGy and would need to be calibrated frequently. Pulse-counting control was accurately implemented with one-to-one correspondence between the intended and the actual delivered pulses. The dose-based control was sufficient to gate on any pulse of the Linac.In vivodosimetry monitoring with a 1 cm circular cut-out revealed that during the ramp-up period, the averageDpwas â¼0.045 ± 0.004 Gy Pulse-1, whereas after the ramp-up it stabilized at 0.65 ± 0.01 Gy Pulse-1.Significance.The tools presented in this study can be used to determine the beam parameter space pertinent to the FLASH effect. Additionally, this study is the first instance of real-time dose-based control for a modified Linac at ultra-high dose rates, which provides insight into the tool required for future clinical translation of FLASH-RT.

##### Assuntos
Aceleradores de Partículas , Radiometria , Animais , Camundongos , Imagens de Fantasmas , Plásticos , Dosagem Radioterapêutica
4.
Med Phys ; 49(6): 4018-4025, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35304768

##### RESUMO

PURPOSE: Imaging Cherenkov light during radiotherapy allows the visualization and recording of frame-by-frame relative maps of the dose being delivered to the tissue at each control point used throughout treatment, providing one of the most complete real-time means of treatment quality assurance. In non-turbid media, the intensity of Cherenkov light is linear with surface dose deposited, however the emission from patient tissue is well-known to be reduced by absorbing tissue components such as hemoglobin, fat, water, and melanin, and diffused by the scattering components of tissue. Earlier studies have shown that bulk correction could be achieved by using the patient planning computed tomography (CT) scan for attenuation correction. METHODS: In this study, CT maps were used for correction of spatial variations in emissivity. Testing was completed on Cherenkov images from radiotherapy treatments of post-lumpectomy breast cancer patients (n = 13), combined with spatial renderings of the patient radiodensity (CT number) from their planning CT scan. RESULTS: The correction technique was shown to provide a pixel-by-pixel correction that suppressed many of the inter- and intra-patient differences in the Cherenkov light emitted per unit dose. This correction was established from a calibration curve that correlated Cherenkov light intensity to surface-rendered CT number ( R 6 MV 2 = 0.70 $R_{6{\rm{MV}}}^2 = 0.70$ and R 10 MV 2 = 0.72 $R_{10{\rm{MV}}}^2 = 0.72$ ). The corrected Cherenkov intensity per unit dose standard error was reduced by nearly half (from â¼30% to â¼17%). CONCLUSIONS: This approach provides evidence that the planning CT scan can mitigate some of the tissue-specific attenuation in Cherenkov images, allowing them to be translated into near surface dose images.

##### Assuntos
5.
Int J Radiat Oncol Biol Phys ; 112(4): 1023-1032, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34762969

##### RESUMO

PURPOSE: To present a Monte Carlo (MC) beam model and its implementation in a clinical treatment planning system (TPS, Varian Eclipse) for a modified ultrahigh dose-rate electron FLASH radiation therapy (eFLASH-RT) linear accelerator (LINAC) using clinical accessories and geometry. METHODS AND MATERIALS: The gantry head without scattering foils or targets, representative of the LINAC modifications, was modeled in the Geant4-based GAMOS MC toolkit. The energy spectrum (σE) and beam source emittance cone angle (Î¸cone) were varied to match the calculated open-field central-axis percent depth dose (PDD) and lateral profiles with Gafchromic film measurements. The beam model and its Eclipse configuration were validated with measured profiles of the open field and nominal fields for clinical applicators. An MC forward dose calculation was conducted for a mouse whole-brain treatment, and an eFLASH-RT plan was compared with a conventional (Conv-) RT electron plan in Eclipse for a human patient with metastatic renal cell carcinoma. RESULTS: The eFLASH beam model agreed best with measurements at σE = 0.5 MeV and Î¸cone = 3.9° ± 0.2°. The model and its Eclipse configuration were validated to clinically acceptable accuracy (the absolute average error was within 1.5% for in-water lateral, 3% for in-air lateral, and 2% for PDDs). The forward calculation showed adequate dose delivery to the entire mouse brain while sparing the organ at risk (lung). The human patient case demonstrated the planning capability with routine accessories to achieve an acceptable plan (90% of the tumor volume receiving 95% and 90% of the prescribed dose for eFLASH and Conv-RT, respectively). CONCLUSIONS: To our knowledge, this is the first functional beam model commissioned in a clinical TPS for eFLASH-RT enabling planning and evaluation with minimal deviation from the Conv-RT workflow. It facilitates the clinical translation because eFLASH-RT and Conv-RT plan quality were comparable for a human patient involving complex geometries and tissue heterogeneity. The methods can be expanded to model other eFLASH irradiators with different beam characteristics.

##### Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Algoritmos , Animais , Elétrons , Humanos , Camundongos , Método de Monte Carlo , Aceleradores de Partículas , Imagens de Fantasmas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos
6.
Light Sci Appl ; 10(1): 226, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737264

##### RESUMO

Color vision is used throughout medicine to interpret the health and status of tissue. Ionizing radiation used in radiation therapy produces broadband white light inside tissue through the Cherenkov effect, and this light is attenuated by tissue features as it leaves the body. In this study, a novel time-gated three-channel camera was developed for the first time and was used to image color Cherenkov emission coming from patients during treatment. The spectral content was interpreted by comparison with imaging calibrated tissue phantoms. Color shades of Cherenkov emission in radiotherapy can be used to interpret tissue blood volume, oxygen saturation and major vessels within the body.

7.
J Biomed Opt ; 26(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34643072

##### RESUMO

SIGNIFICANCE: The Cherenkov emission spectrum overlaps with that of ambient room light sources. Choice of room lighting devices dramatically affects the efficient detection of Cherenkov emission during patient treatment. AIM: To determine optimal room light sources allowing Cherenkov emission imaging in normally lit radiotherapy treatment delivery rooms. APPROACH: A variety of commercial light sources and long-pass (LP) filters were surveyed for spectral band separation from the red to near-infrared Cherenkov light emitted by tissue. Their effects on signal-to-noise ratio (SNR), Cherenkov to background signal ratio, and image artifacts were quantified by imaging irradiated tissue equivalent phantoms with an intensified time-gated CMOS camera. RESULTS: Because Cherenkov emission from tissue lies largely in the near-infrared spectrum, a controlled choice of ambient light that avoids this spectral band is ideal, along with a camera that is maximally sensitive to it. An RGB LED light source produced the best SNR out of all sources that mimic room light temperature. A 675-nm LP filter on the camera input further reduced ambient light detected (optical density > 3), achieving maximal SNR for Cherenkov emission near 40. Reduction of the room light signal reduced artifacts from specular reflection on the tissue surface and also minimized spurious Cherenkov signals from non-tissue features such as bolus. CONCLUSIONS: LP filtering during image acquisition for near-infrared light in tandem with narrow band LED illuminated rooms improves image quality, trading off the loss of red wavelengths for better removal of room light in the image. This spectral filtering is also critically important to remove specular reflection in the images and allow for imaging of Cherenkov emission through clear bolus. Beyond time-gated external beam therapy systems, the spectral separation methods can be utilized for background removal for continuous treatment delivery methods including proton pencil beam scanning systems and brachytherapy.

##### Assuntos
Raios Infravermelhos , Radiometria , Humanos , Imagem Óptica , Imagens de Fantasmas , Razão Sinal-Ruído
8.
J Biomed Opt ; 26(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34545714

##### RESUMO

SIGNIFICANCE: Optical imaging of Cherenkov emission during radiation therapy could be used to verify dose delivery in real-time if a more comprehensive quantitative understanding of the factors affecting emission intensity could be developed. AIM: This study aims to explore the change in diffuse Cherenkov emission intensity with x-ray beam energy from irradiated tissue, both theoretically and experimentally. APPROACH: Derivation of the emitted Cherenkov signal was achieved using diffusion theory, and experimental studies with 6 to 18 MV energy x-rays were performed in tissue phantoms to confirm the model predictions as related to the radiation build-up factor with depth into tissue. RESULTS: Irradiation at lower x-ray energies results in a greater surface dose and higher build-up slope, which results in a â¼46 % greater diffusely emitted Cherenkov signal per unit dose at 6 MV relative to 18 MV x-rays. However, this phenomenon competes with a decrease in signal from less Cherenkov photons being generated at lower energies, a â¼44 % reduction at 6 versus 18 MV. The result is an emitted Cherenkov signal that is nearly constant with beam energy. CONCLUSIONS: This study explains why the observed Cherenkov emission from tissue is not a strong function of beam energy, despite the known strong correlation between Cherenkov intensity and particle energy in the absence of build-up and scattering effects.

##### Assuntos
Fótons , Imagens de Fantasmas , Raios X
9.
J Appl Clin Med Phys ; 22(9): 252-261, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34409766

##### RESUMO

PURPOSE: Demonstrate a novel phantom design using a remote camera imaging method capable of concurrently measuring the position of the x-ray isocenter and the magnetic resonance imaging (MRI) isocenter on an MR-linac. METHODS: A conical frustum with distinct geometric features was machined out of plastic. The phantom was submerged in a small water tank, and aligned using room lasers on a MRIdian MR-linac (ViewRay Inc., Cleveland, OH). The phantom physical isocenter was visualized in the MR images and related to the DICOM coordinate isocenter. To view the x-ray isocenter, an intensified CMOS camera system (DoseOptics LLC., Hanover, NH) was placed at the foot of the treatment couch, and centered such that the optical axis of the camera was coincident with the central axis of the treatment bore. Two or four 8.3mm x 24.1cm beams irradiated the phantom from cardinal directions, producing an optical ring on the conical surface of the phantom. The diameter of the ring, measured at the peak intensity, was compared to the known diameter at the position of irradiation to determine the Z-direction offset of the beam. A star-shot method was employed on the front face of the frustum to determine X-Y alignment of the MV beam. Known shifts were applied to the phantom to establish the sensitivity of the method. RESULTS: Couch translations, demonstrative of possible isocenter misalignments, on the order of 1mm were detectable for both the radiotherapy and MRI isocenters. Data acquired on the MR-linac demonstrated an average error of 0.28mm(N=10, R2 =0.997, σ=0.37mm) in established Z displacement, and 0.10mm(N=5, σ=0.34mm) in XY directions of the radiotherapy isocenter. CONCLUSIONS: The phantom was capable of measuring both the MRI and radiotherapy treatment isocenters. This method has the potential to be of use in MR-linac commissioning, and could be streamlined to be valuable in daily constancy checks of isocenter coincidence.

##### Assuntos
10.
J Radiat Res ; 62(5): 833-840, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34247250

##### RESUMO

X-ray induced molecular luminescence (XML) is a phenomenon that can be utilized for clinical, deep-tissue functional imaging of tailored molecular probes. In this study, a survey of common or clinically approved fluorophores was carried out for their megavoltage X-ray induced excitation and emission characteristics. We find that direct scintillation effects and Cherenkov generation are two possible ways to cause these molecules' excitation. To distinguish the contributions of each excitation mechanism, we exploited the dependency of Cherenkov radiation yield on X-ray energy. The probes were irradiated by constant dose of 6 MV and 18 MV X-ray radiation, and their relative emission intensities and spectra were quantified for each X-ray energy pair. From the ratios of XML, yield for 6 MV and 18 MV irradiation we found that the Cherenkov radiation dominated as an excitation mechanism, except for aluminum phthalocyanine, which exhibited substantial scintillation. The highest emission yields were detected from fluorescein, proflavin and aluminum phthalocyanine, in that order. XML yield was found to be affected by the emission quantum yield, overlap of the fluorescence excitation and Cherenkov emission spectra, scintillation yield. Considering all these factors and XML emission spectrum respective to tissue optical window, aluminum phthalocyanine offers the best XML yield for deep tissue use, while fluorescein and proflavine are most useful for subcutaneous or superficial use.

##### Assuntos
Corantes Fluorescentes/efeitos da radiação , Luminescência , Avaliação Pré-Clínica de Medicamentos , Desenho de Equipamento , Fluoresceína/efeitos da radiação , Humanos , Indóis/efeitos da radiação , Isoindóis/efeitos da radiação , Azul de Metileno/efeitos da radiação , Compostos Organometálicos/efeitos da radiação , Aceleradores de Partículas , Proflavina/efeitos da radiação , Protoporfirinas/efeitos da radiação , Solventes , Espectrometria de Fluorescência , Verteporfina/efeitos da radiação , Raios X
11.
Artigo em Inglês | MEDLINE | ID: mdl-34083857

##### RESUMO

Total Skin Electron Therapy (TSET) utilizes high-energy electrons to treat cancers on the entire body surface. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interaction between the high-energy electron beam and tissue. Cherenkov emission can be used to evaluate the dose uniformity on the surface of the patient in real-time using a time-gated intensified camera system. Each patient was monitored during TSET by in-vivo detectors (IVD) as well as Scintillators. Patients undergoing TSET in various conditions (whole body and half body) were imaged and analyzed. A rigorous methodology for converting Cherenkov intensity to surface dose as products of correction factors, including camera vignette correction factor, incident radiation correction factor, and tissue optical properties correction factor. A comprehensive study has been carried out by inspecting various positions on the patients such as vertex, chest, perineum, shins, and foot relative to the umbilicus point (the prescription point).

12.
Phys Med Biol ; 66(13)2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34015774

##### RESUMO

Purpose.In this study, spatio-temporal beam profiling for electron ultra-high dose rate (UHDR; >40 Gy s-1) radiation via Cherenkov emission and radioluminescence imaging was investigated using intensified complementary metal-oxide-semiconductor cameras.Methods.The cameras, gated to FLASH optimized linear accelerator pulses, imaged radioluminescence and Cherenkov emission incited by single pulses of a UHDR (>40 Gy s-1) 10 MeV electron beam delivered to the isocenter. Surface dosimetry was investigated via imaging Cherenkov emission or scintillation from a solid water phantom or Gd2O2S:Tb screen positioned on top of the phantom, respectively. Projected depth-dose profiles were imaged from a tank filled with water (Cherenkov emission) and a 1 g l-1quinine sulfate solution (scintillation). These optical results were compared with projected lateral dose profiles measured by Gafchromic film at different depths, including the surface.Results.The per-pulse beam output from Cherenkov imaging agreed with the photomultiplier tube Cherenkov output to within 3% after about the first five to seven ramp-up pulses. Cherenkov emission and scintillation were linear with dose (R2 = 0.987 and 0.995, respectively) and independent of dose rate from â¼50 to 300 Gy s-1(0.18-0.91 Gy/pulse). The surface dose distribution from film agreed better with scintillation than with Cherenkov emission imaging (3%/3 mm gamma pass rates of 98.9% and 88.8%, respectively). Using a 450 nm bandpass filter, the quinine sulfate-based water imaging of the projected depth optical profiles agreed with the projected film dose to within 5%.Conclusion.The agreement of surface dosimetry using scintillation screen imaging and Gafchromic film suggests it can verify the consistency of daily beam quality assurance parameters with an accuracy of around 2% or 2 mm. Cherenkov-based surface dosimetry was affected by the target's optical properties, prompting additional calibration. In projected depth-dose profiling, scintillation imaging via spectral suppression of Cherenkov emission provided the best match to film. Both camera-based imaging modalities resolved dose from single UHDR beam pulses of up to 60 Hz repetition rate and 1 mm spatial resolution.

##### Assuntos
Elétrons , Radiometria , Imagem Óptica , Aceleradores de Partículas , Imagens de Fantasmas
13.
Int J Radiat Oncol Biol Phys ; 111(1): 240-248, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33845146

##### Assuntos
Neoplasias Experimentais/radioterapia , Oxigênio/análise , Animais , Camundongos , Neoplasias Experimentais/metabolismo , Consumo de Oxigênio , Dosagem Radioterapêutica
14.
Int J Radiat Oncol Biol Phys ; 110(3): 909-910, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33811977
15.
Radiother Oncol ; 160: 90-96, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33892022

##### RESUMO

PURPOSE: In mono-isocentric radiation therapy treatment plans designed to treat the whole breast and supraclavicular lymph nodes, the fields meet at isocenter, forming the match line. Insufficient coverage at the match line can lead to recurrence, and overlap over weeks of treatment can lead to increased risk of healthy tissue toxicity. Cherenkov imaging was used to assess the accuracy of delivery at the match line and identify potential incidents during patient treatments. METHODS AND MATERIALS: A controlled calibration was constructed from the deconvolved Cherenkov images from the delivery of a modified patient treatment plan to an anthropomorphic phantom with introduced separation and overlap. The trend from this calibration was then used to evaluate the field match line for accuracy and inter-fraction consistency for two patients. RESULTS: The intersection point between matching field profiles was directly correlated to the distance (gap/overlap) between the fields (anthropomorphic phantom R2 = 0.994 "breath hold" and R2 = 0.990 "free breathing"). The profile intersection points from two patients' imaging sessions yielded an average of +1.40 mm offset (overlap) and -1.32 mm offset (gap), thereby introducing roughly a 25.0% over-dose and a -23.6% under-dose (R2 = 0.994). CONCLUSIONS: This study shows that field match regions can be detected and quantified by taking deconvolved Cherenkov images and using their product image to create steep intensity gradients, causing match lines to stand out. These regions can then be quantitatively translated into a dose consequence. This approach offers a high sensitivity detection method which can quantify match line variability and errors in vivo.

##### Assuntos
16.
Med Phys ; 48(6): 2750-2759, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33887796

##### RESUMO

PURPOSE: This study demonstrates a robust Cherenkov imaging-based solution to MR-Linac daily QA, including mechanical-imaging-radiation isocenter coincidence verification. METHODS: A fully enclosed acrylic cylindrical phantom was designed to be mountable to the existing jig, indexable to the treatment couch. An ABS plastic conical structure was fixed inside the phantom, held in place with 3D-printed spacers, and filled with water allowing for high edge contrast on MR imaging scans. Both a star shot plan and a four-angle sheet beam plan were delivered to the phantom; the former allowed for radiation isocenter localization in the x-z plane (A/P and L/R directions) relative to physical landmarks on the phantom, and the latter allowed for the longitudinal position of the sheet beam to be encoded as a ring of Cherenkov radiation emitted from the phantom, allowing for isocenter localization on the y-axis (S/I directions). A custom software application was developed to perform near-real-time analysis of the data by any clinical user. RESULTS: Calibration procedures show that linearity between longitudinal position and optical ring diameter is high (R2  > 0.99), and that RMSE is low (0.184 mm). The star shot analysis showed a minimum circle radius of 0.34 mm. The final isocenter coincidence measurements in the lateral, longitudinal, and vertical directions were -0.61 mm, 0.55 mm, and -0.14 mm, respectively, and the total 3D distance coincidence was 0.83 mm, with each of these being below 2 mm tolerance. CONCLUSION: This novel system provided an efficient, MR safe, all-in-one method for acquisition and near-real-time analysis of isocenter coincidence data. This represents a direct measurement of the 3D isocentricity. The combination of this phantom and the custom analysis application makes this solution readily clinically deployable after the longitudinal analysis of performance consistency.

##### Assuntos
Imageamento por Ressonância Magnética , Aceleradores de Partículas , Calibragem , Imagens de Fantasmas , Software
17.
Med Phys ; 48(5): 2673-2681, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33730367

##### RESUMO

PURPOSE: High dose rate conditions, coupled with problems related to small field dosimetry, make dose characterization for FLASH-RT challenging. Most conventional dosimeters show significant dependence on dose rate at ultra-high dose rate conditions or fail to provide sufficiently fast temporal data for pulse to pulse dosimetry. Here fast 2D imaging of radioluminescence from a water and quinine phantom was tested for dosimetry of individual 4 µs linac pulses. METHODS: A modified clinical linac delivered an electron FLASH beam of >50 Gy/s to clinical isocenter. This modification removed the x-ray target and flattening filter, leading to a beam that was symmetric and gaussian, as verified with GafChromic EBT-XD film. Lateral projected 2D dose distributions for each linac pulse were imaged in a quinine-doped water tank using a gated intensified camera, and an inverse Abel transform reconstruction provided 3D images for on-axis depth dose values. A total of 20 pulses were delivered with a 10 MeV, 1.5 cm circular beam, and beam with jaws wide open (40 × 40 cm2 ), and a 3D dose distribution was recovered for each pulse. Beam output was analyzed on a pulse by pulse basis. RESULTS: The Rp , Dmax , and the R50 measured with film and optical methods agreed to within 1 mm for the 1.5 cm circular beam and the beam with jaws wide open. Cross beam profiles for both beams agreed with film data with >95% passing rate (2%/2 mm gamma criteria). The optical central axis depth dose agreed with film data, except for near the surface. A temporal pulse analysis revealed a ramp-up period where the dose per pulse increased for the first few pulses and then stabilized. CONCLUSIONS: Optical imaging of radioluminescence was presented as a valuable tool for establishing a baseline for the recently initiated electron FLASH beam at our institution.

##### Assuntos
18.
Int J Radiat Oncol Biol Phys ; 110(3): 872-882, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33444695

##### RESUMO

PURPOSE: In this study, procedures were developed to achieve efficient reversible conversion of a clinical linear accelerator (LINAC) and deliver ultrahigh-dose-rate (UHDR) electron or conventional beams to the treatment room isocenter for FLASH radiation therapy. METHODS AND MATERIALS: The LINAC was converted to deliver UHDR beam within 20 minutes by retracting the x-ray target from the beam's path, positioning the carousel on an empty port, and selecting 10 MV photon beam energy in the treatment console. Dose rate surface and depth dose profiles were measured in solid water phantom at different field sizes with Gafchromic film and an optically stimulated luminescent dosimeter (OSLD). A pulse controller counted the pulses via scattered radiation signal and gated the delivery for a preset pulse count. A fast photomultiplier tube-based Cherenkov detector measured the per pulse beam output at a 2-ns sampling rate. After conversion back to clinical mode, conventional beam output, flatness, symmetry, field size, and energy were measured for all clinically commissioned energies. RESULTS: The surface average dose rates at the isocenter for 1-cm diameter and 1.5-in diameter circular fields and for a jaws-wide-open field were 238 ± 5 Gy/s, 262 ± 5 Gy/s, and 290 ± 5 Gy/s, respectively. The radial symmetry of the beams was within 2.4%, 0.5%, and 0.2%, respectively. The doses from simultaneous irradiation of film and OSLD were within 1%. The photomultiplier tube showed the LINAC required ramp up time in the first 4 to 6 pulses before the output stabilized, after which its stability was within 3%. CONCLUSIONS: At the isocenter of the treatment room, 10 MeV UHDR beams were achieved. The beam output was reproducible but requires further investigation of the ramp up time, equivalent to â¼1 Gy, requiring dose monitoring. The UHDR beam can irradiate both small and large subjects to investigate potential FLASH radiobiological effects in minimally modified clinical settings, and the dose rate can be further increased by reducing the source-to-surface distance.

##### Assuntos
Elétrons , Aceleradores de Partículas , Humanos , Imagens de Fantasmas
19.
J Biomed Opt ; 26(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33386709

##### RESUMO

SIGNIFICANCE: Deep-tissue penetration by x-rays to induce optical responses of specific molecular reporters is a new way to sense and image features of tissue function in vivo. Advances in this field are emerging, as biocompatible probes are invented along with innovations in how to optimally utilize x-ray sources. AIM: A comprehensive review is provided of the many tools and techniques developed for x-ray-induced optical molecular sensing, covering topics ranging from foundations of x-ray fluorescence imaging and x-ray tomography to the adaptation of these methods for sensing and imaging in vivo. APPROACH: The ways in which x-rays can interact with molecules and lead to their optical luminescence are reviewed, including temporal methods based on gated acquisition and multipoint scanning for improved lateral or axial resolution. RESULTS: While some known probes can generate light upon x-ray scintillation, there has been an emergent recognition that excitation of molecular probes by x-ray-induced Cherenkov light is also possible. Emission of Cherenkov radiation requires a threshold energy of x-rays in the high kV or MV range, but has the advantage of being able to excite a broad range of optical molecular probes. In comparison, most scintillating agents are more readily activated by lower keV x-ray energies but are composed of crystalline inorganic constituents, although some organic biocompatible agents have been designed as well. Methods to create high-resolution structured x-ray-optical images are now available, based upon unique scanning approaches and/or a priori knowledge of the scanned x-ray beam geometry. Further improvements in spatial resolution can be achieved by careful system design and algorithm optimization. Current applications of these hybrid x-ray-optical approaches include imaging of tissue oxygenation and pH as well as of certain fluorescent proteins. CONCLUSIONS: Discovery of x-ray-excited reporters combined with optimized x-ray scan sequences can improve imaging resolution and sensitivity.

##### Assuntos
Luminescência , Imagem Molecular , Imagem Óptica , Imagens de Fantasmas , Radiografia , Raios X
20.
J Biomed Opt ; 26(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33423407

##### RESUMO

SIGNIFICANCE: The study has confirmed the feasibility of using ultraviolet (UV) excitation to visualize and quantify desmoplasia in fresh tumor tissue of pancreatic adenocarcinoma (PDAC) in an orthotopic xenograft mouse model, which provides a useful imaging platform to evaluate acute therapeutic responses. AIM: Stromal network of collagen prominent in PDAC tumors is examined by imaging fresh tissue samples stained with histological dyes. Fluorescence signals are color-transferred to mimic Masson's trichrome staining. APPROACH: Murine tumor samples were stained with Hoechst, eosin, and rhodamine B and excited at 275-nm. Fluorescence signals in the visible spectrum were captured by a CMOS color camera with high contrast and resolution at whole-tumor slice field of view. RESULTS: Fluorescence imaging using UV excitation is capable of visualizing collagen deposition in PDAC tumors. Both fluorescence and histology data showed collagen content of up to 30%. The collagen modulation effect due to photodynamic priming treatment was observed showing 13% of collagen reduction. Necrosis area is visible and perfusion imaging using Texas Red dextran is feasible. CONCLUSIONS: The study demonstrates collagen visualization in fresh PDAC tumor samples using UV excitation. This imaging platform also provides quantitative stromal information from fiber analysis and visibility of necrosis and perfusion, suitable for therapeutic response assessment of photodynamic therapy.

##### Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Fotoquimioterapia , Animais , Colágeno , Camundongos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico
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