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1.
J Biomed Opt ; 26(1)2021 Jan.
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.

2.
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 ∼1 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.

3.
Phys Med Biol ; 65(22): 225013, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179612

RESUMO

In this study the metric of detective quantum efficiency (DQE) was applied to Cherenkov imaging systems for the first time, and results were compared for different detector hardware, gain levels and with imaging processing for noise suppression. Intensified complementary metal oxide semiconductor cameras using different image intensifier designs (Gen3 and Gen2+) were used to image Cherenkov emission from a tissue phantom in order to measure the modulation transfer function (MTF) and noise power spectrum (NPS) of the systems. These parameters were used to calculate the DQE for varying acquisition settings and image processing steps. MTF curves indicated that the Gen3 system had superior contrast transfer and spatial resolution than the Gen2+ system, with [Formula: see text] values of 0.52 mm-1 and 0.31 mm-1, respectively. With median filtering for noise suppression, these values decreased to 0.50 mm-1 and 0.26 mm-1. The maximum NPS values for the Gen3 and Gen2+ systems at high gain were 1.3 × 106 mm2 and 9.1 × 104 mm2 respectively, representing a 14x decrease in noise power for the Gen2+ system. Both systems exhibited increased NPS intensity with increasing gain, while median filtering lowered the NPS. The DQE of each system increased with increasing gain, and at the maximum gain levels the Gen3 system had a low-frequency DQE of 0.31%, while the Gen2+ system had a value of 1.44%. However, at a higher frequency of 0.4 mm-1, these values became 0.54% and 0.03%. Filtering improved DQE for the Gen3 system and reduced DQE for the Gen2+ system and had a mix of detrimental and beneficial qualitative effects by decreasing the spatial resolution and sharpness but also substantially lowering noise. This methodology for DQE measurement allowed for quantitative comparison between Cherenkov imaging cameras and improvements to their sensitivity, and yielded the first formal assessment of Cherenkov image formation efficiency.

4.
Med Phys ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030241

RESUMO

PURPOSE: A Geant4-based TOPAS Monte Carlo toolkit was utilized to model a Varian ProBeam proton therapy system, with the aim of providing an independent computational platform for validating advanced dosimetric methods. MATERIALS AND METHODS: The model was tested for accuracy of dose and linear energy transfer (LET) prediction relative to the commissioning data, which included integral depth dose (IDD) in water and spot profiles in air measured at varying depths (for energies of 70 to 240 MeV in increments of 10 MeV, and 242 MeV), and absolute dose calibration. Emittance was defined based on depth-dependent spot profiles and Courant-Snyder's particle transport theory, which provided spot size and angular divergence along the inline and crossline plane. Energy spectra were defined as Gaussian distributions that best matched the range and maximum dose of the IDD. The validity of the model was assessed based on measurements of range, dose to peak difference, mean point to point difference, spot sizes at different depths, and spread-out Bragg peak (SOBP) IDD and was compared to the current treatment planning software (TPS). RESULTS: Simulated and commissioned spot sizes agreed within 2.5%. The single spot IDD range, maximum dose, and mean point to point difference of each commissioned energy agreed with the simulated profiles generally within 0.07 mm, 0.4%, and 0.6%, respectively. A simulated SOBP plan agreed with the measured dose within 2% for the plateau region. The protons/MU and absolute dose agreed with the current TPS to within 1.6% and exhibited the greatest discrepancy at higher energies. CONCLUSIONS: The TOPAS model agreed well with the commissioning data and included inline and crossline asymmetry of the beam profiles. The discrepancy between the measured and TOPAS-simulated SOBP plan may be due to beam modeling simplifications of the current TPS and the nuclear halo effect. The model can compute LET, and motivates future studies in understanding equivalent dose prediction in treatment planning, and investigating scintillation quenching.

5.
Phys Med Biol ; 65(14): 145001, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32498053

RESUMO

In proton-based radiotherapy, proton radiography could allow for direct measurement of the water-equivalent path length (WEPL) in tissue, which can then be used to determine relative stopping power (RSP). Additionally, proton radiographs allow for imaging in the beam's-eye-view. In this work, a proton radiography technique using a flat-panel imager and a pencil-beam scanning (PBS) system is demonstrated in phantom. Proton PBS plans were delivered on a Varian ProBeam system to a flat-panel imager. Each proton plan consisted of energy layers separated by 4.8 MeV, and a field size of 25 cm × 25 cm. All measured data is binned into a layer-by-layer delivery in post processing. To build a calibration curve correlating detector response to WEPL, the plans were delivered to slabs of solid water of increasing thickness. Pixel-by-pixel detector response in the time/energy domain is then fit as a function of WEPL. Tissue equivalent phantoms are imaged for evaluation of WEPL accuracy. A spatial resolution phantom and a head phantom are also imaged. For all experiments, the detector was run with an effective pixel size of 0.4 mm × 0.4 mm. The proposed method reconstructed RSP with mean errors of 2.65%, -0.14%, and 0.61% for lung, soft tissue, and bone, respectively. In a 40 mm thick spatial resolution phantom, a 2 mm deep pinhole with 1 mm diameter can be seen. The accuracy and spatial resolution of the method show that it could be implemented for patient position verification. Further development could lead to patient-specific verification of RSP to be used for treatment guidance.


Assuntos
Terapia com Prótons , Prótons , Radiografia/instrumentação , Calibragem , Cabeça , Humanos , Imagens de Fantasmas , Água
6.
Med Phys ; 47(9): 3861-3869, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32583484

RESUMO

PURPOSE: To demonstrate the potential benefits of remote camera-based scintillation imaging for routine quality assurance (QA) measurements for magnetic resonance guided radiotherapy (MRgRT) linear accelerators. METHODS: A wall-mounted CMOS camera with a time-synchronized intensifier was used to image photons produced from a scintillation screen in response to dose deposition from a 6 MV FFF x-ray beam produced by a 0.35 T MR-linac. The oblique angle of the field of view was corrected using a projective transform from a checkerboard calibration target. Output sensitivity and constancy was measured using the scintillator and benchmarked against an A28 ion chamber. Field cross-plane and in-plane profiles were measured for field sizes ranging from 1.68 × 1.66 cm2 to 20.02 × 19.92 cm2 with both scintillation imaging and using an IC profiler. Multileaf collimator (MLC) shifts were introduced to test sensitivity of the scintillation imaging system to small spatial deviations. A picket fence test and star-shot were delivered to both the scintillator and EBT3 film to compare accuracy in measuring MLC positions and isocenter size. RESULTS: The scintillation imaging system showed comparable sensitivity and linearity to the ion chamber in response to changes in machine output down to 0.5 MU (R2  = 0.99). Cross-plane profiles show strong agreement with defined field sizes using full width half maximum (FWHM) measurement of <2 mm for field sizes below 15 cm, but the oblique viewing angle was the limiting factor in accuracy of in-plane profile widths. However, the system provided high-resolution profiles in both directions for constancy measurements. Small shifts in the field position down to 0.5 mm were detectable with <0.1 mm accuracy. Multileaf collimator positions as measured with both scintillation imaging and EBT3 film were measured within ± 1 mm tolerance and both detection systems produced similar isocenter sizes from the star-shot analysis (0.81 and 0.83 mm radii). CONCLUSIONS: Remote scintillation imaging of a two-dimensional screen provided a rapid, versatile, MR-compatible solution to many routine quality assurance procedures including output constancy, profile flatness and symmetry constancy, MLC position verification and isocenter size. This method is high-resolution, does not require post-irradiation readout, and provides simple, instantaneous data acquisition. Full automation of the readout and processing could make this a very simple but effective QA tool, and is adaptable to all medical accelerators.

7.
Phys Med Biol ; 65(16): 165014, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32428888

RESUMO

The goal of this work was to create a technique that could measure all possible spatial and temporal delivery rates used in pencil-beam scanning (PBS) proton therapy. The proposed system used a fast scintillation screen for full-field imaging to resolve temporal and spatial patterns as it was delivered. A fast intensified CMOS camera used continuous mode with 10 ms temporal frame rate and 1 × 1 mm2 spatial resolution, imaging a scintillation screen during clinical proton PBS delivery. PBS plans with varying dose, dose rate, energy, field size, and spot-spacing were generated, delivered and imaged. The captured images were post processed to provide dose and dose rate values after background subtraction, perspective transformation, uniformity correction for the camera and the scintillation screen, and calibration into dose. The linearity in scintillation response with respect to varying dose rate, dose, and field size was within 2%. The quenching corrected response with varying energy was also within 2%. Large spatio-temporal variations in dose rate were observed, even for plans delivered with similar dose distributions. Dose and dose rate histograms and maximum dose rate maps were generated for quantitative evaluations. With the fastest PBS delivery on a clinical system, dose rates up to 26.0 Gy s-1 were resolved. The scintillation imaging technique was able to quantify proton PBS dose rate profiles with spot weight as low as 2 MU, with spot-spacing of 2.5 mm, having a 1 × 1 mm2 spatial resolution. These dose rate temporal profiles, spatial maps, and cumulative dose rate histograms provide useful metrics for the potential evaluation and optimization of dose rate in treatment plans.


Assuntos
Imagem Molecular/métodos , Terapia com Prótons , Doses de Radiação , Calibragem , Dosagem Radioterapêutica , Radioterapia Guiada por Imagem
8.
Med Phys ; 47(8): 3485-3495, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32319098

RESUMO

PURPOSE: In this study, we investigated computationally and experimentally a hexagonal-pattern array of spatially fractionated proton minibeams produced by proton pencil beam scanning (PBS) technique. Spatial fractionation of dose delivery with millimeter or submillimeter beam size has proven to be a promising approach to significantly increase the normal tissue tolerance. Our goals are to obtain an optimized minibeam design and to show that it is feasible to implement the optimized minibeams at the existing proton clinics. METHODS: An optimized minibeam arrangement is one that would produce high peak-to-valley dose ratios (PVDRs) in normal tissues and a PVDR approaching unity at the Bragg peak. Using Monte Carlo (MC) code TOPAS we simulated proton pencil beams that mimic those available at the existing proton therapy facilities and obtained a hexagonal-pattern array of minibeams by collimating the proton pencil beams through the 1-3 mm diameter pinholes of a collimator. We optimized the minibeam design by considering different combinations of parameters including collimator material and thickness (t), center-to-center (c-t-c) distance, and beam size. The optimized minibeam design was then evaluated for normal tissue sparing against the uniform pencil beam scanning (PBS) by calculating the therapeutic advantage (TA) in terms of cell survival fraction. Verification measurements using radiochromic films were performed at the Emory proton therapy center (EPTC). RESULTS: Optimized hexagonal-pattern minibeams having PVDRs of >10 at phantom surface and of >3 at depths up to 6 cm were achieved with 2 mm diameter modulated proton minibeams (with proton energies between 120 and 140 MeV) corresponding to a spread-out-Bragg-peak (SOBP) over the depth of 10-14 cm. The results of the film measurements agree with the MC results within 10%. The TA of the 2 mm minibeams against the uniform PBS is >3 from phantom surface to the depth of 5 cm and then smoothly drops to ~1.5 as it approaches the proximal edge of the SOBP. For 2 mm minibeams and 6 mm c-t-c distance, we delivered 1.72 Gy at SOBP for 7.2 × 7.2 × 4 cm3 volume in 48 s. CONCLUSIONS: We conclude that it is feasible to implement the optimized hexagonal-pattern 2 mm proton minibeam radiotherapy at the existing proton clinics, because desirable PVDRs and TAs are achievable and the treatment time is reasonable.

9.
Med Phys ; 47(4): 1545-1557, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31945191

RESUMO

PURPOSE: Treatment planning systems (TPSs) from different vendors can involve different implementations of Monte Carlo dose calculation (MCDC) algorithms for pencil beam scanning (PBS) proton therapy. There are currently no guidelines for validating non-water materials in TPSs. Furthermore, PBS-specific parameters can vary by 1-2 orders of magnitude among different treatment delivery systems (TDSs). This paper proposes a standardized framework on the use of commissioning data and steps to validate TDS-specific parameters and TPS-specific heterogeneity modeling to potentially reduce these uncertainties. METHODS: A standardized commissioning framework was developed to commission the MCDC algorithms of RayStation 8A and Eclipse AcurosPT v13.7.20 using water and non-water materials. Measurements included Bragg peak depth-dose and lateral spot profiles and scanning field outputs for Varian ProBeam. The phase-space parameters were obtained from in-air measurements and the number of protons per MU from output measurements of 10 × 10 cm2 square fields at a 2 cm depth. Spot profiles and various PBS field measurements at additional depths were used to validate TPS. Human tissues in TPS, Gammex phantom materials, and artificial materials were used for the TPS benchmark and validation. RESULTS: The maximum differences of phase parameters, spot sigma, and divergence between MCDC algorithms are below 4.5 µm and 0.26 mrad in air, respectively. Comparing TPS to measurements at depths, both MC algorithms predict the spot sigma within 0.5 mm uncertainty intervals, the resolution of the measurement device. Beam Configuration in AcurosPT is found to underestimate number of protons per MU by ~2.5% and requires user adjustment to match measured data, while RayStation is within 1% of measurements using Auto model. A solid water phantom was used to validate the range accuracy of non-water materials within 1% in AcurosPT. CONCLUSIONS: The proposed standardized commissioning framework can detect potential issues during PBS TPS MCDC commissioning processes, and potentially can shorten commissioning time and improve dosimetric accuracies. Secondary MCDC can be used to identify the root sources of disagreement between primary MCDC and measurement.

10.
J Appl Clin Med Phys ; 21(1): 197-204, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793202

RESUMO

PURPOSE: For pencil-beam scanning proton therapy systems, in-air non-Gaussian halo can significantly impact output at small field sizes and low energies. Since the low-intensity tail of spot profile (halo) is not necessarily modeled in treatment planning systems (TPSs), this can potentially lead to significant differences in patient dose distribution. In this work, we report such impact for a Varian ProBeam system. METHODS: We use a pair magnification technique to measure two-dimensional (2D) spot profiles of protons from 70 to 242 MeV at the treatment isocenter and 30 cm upstream of the isocenter. Measurements are made with both Gafchromic film and a scintillator detector coupled to a CCD camera (IBA Lynx). Spot profiles are measured down to 0.01% of their maximum intensity. Field size factors (FSFs) are compared among calculation using measured 2D profiles, calculation using a clinical treatment planning algorithm (Raystation 8A clinical Monte Carlo), and a CC04 small-volume ion chamber. FSFs were measured for square fields of proton energies ranging from 70 to 242 MeV. RESULTS: All film and Lynx measurements agree within 1 mm for full width at half maximum beam intensity. The measured radial spot profiles disagree with simple Gaussian approximations, which are used for modeling in the TPS. FSF measurements show the magnitude of disagreements between beam output in reality and in the TPS without modeling halo. We found that the clinical TPS overestimated output by as much as 6% for small field sizes of 2 cm at the lowest energy of 70 MeV while the film and Lynx measurements agreed within 4% and 1%, respectively, for this FSF. CONCLUSIONS: If the in-air halo for low-energy proton beams is not fully modeled by the TPS, this could potentially lead to under-dosing small, shallow treatment volumes in PBS treatment plans.


Assuntos
Algoritmos , Terapia com Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Método de Monte Carlo , Distribuição Normal , Dosagem Radioterapêutica
11.
Biomed Phys Eng Express ; 6(3): 035029, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33438674

RESUMO

Purpose; For shoot-through proton treatments, like FLASH radiotherapy, there will be protons exiting the patient which can be used for proton portal imaging (PPI), revealing valuable information for the validation of tumor location in the beam's-eye-view at native gantry angles. However, PPI has poor inherent contrast and spatial resolution. To deal with this issue, we propose a deep-learning-based method to use kV digitally reconstructed radiographs (DRR) to improve PPI image quality. Method; We used a residual generative adversarial network (GAN) framework to learn the nonlinear mapping between PPIs and DRRs. Residual blocks were used to force the model to focus on the structural differences between DRR and PPI. To assess the accuracy of our method, we used 149 images for training and 30 images for testing. PPIs were acquired using a double-scattered proton beam. The DRRs acquired from CT acted as learning targets in the training process and were used to evaluate results from the proposed method using a six-fold cross-validation scheme. Results; Qualitatively, the corrected PPIs showed enhanced spatial resolution and captured fine details present in the DRRs that are missed in the PPIs. The quantitative results for corrected PPIs show average normalized mean error (NME), normalized mean absolute error (NMAE), peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) index of -0.1%, 0.3%, 39.14 dB, and 0.987, respectively. Conclusion; The results indicate the proposed method can generate high quality corrected PPIs and this work shows the potential to use a deep-learning model to make PPI available in proton radiotherapy. This will allow for beam's-eye-view (BEV) imaging with the particle used for treatment, leading to a valuable alternative to orthogonal x-rays or cone-beam CT for patient position verification.

12.
Med Phys ; 46(8): 3674-3678, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152565

RESUMO

PURPOSE: The aim of this study was to create an optical imaging-based system for quality assurance (QA) testing of a dedicated Co-60 total body irradiation (TBI) machine. Our goal is to streamline the QA process by minimizing the amount time necessary for tests such as verification of dose rate and field homogeneity. METHODS: Plastic scintillating rods were placed directly on the patient treatment couch of a dedicated TBI 60 Co irradiator. A tripod-mounted intensified camera was placed directly adjacent to the couch. Images were acquired over a 30-s period once the cobalt source was fully exposed. Real-time image filtering was used; cumulative images were flatfield corrected as well as background and darkfield subtracted. Scintillators were used to measure light-radiation field correspondence, dose rate, field homogeneity, and symmetry. Dose rate effects were measured by modifying the height of the treatment couch and scintillator response was compared to ionization chamber (IC) measurements. Optically stimulated luminesce detector (OSLD) used as reference dosimeters during field symmetry and homogeneity testing. RESULTS: The scintillator-based system accurately reported changes in dose rate. When comparing normalized output values for IC vs scintillators over a range of source-to-surface distances, a linear relationship (R2  = 0.99) was observed. Normalized scintillator signal matched OSLD measurements with <1.5% difference during field homogeneity and symmetry testing. Beam symmetry across both axes of the field was within 2%. The light field was found to correspond to 90 ± 3% of the isodose maximum along the longitudinal and latitudinal axis, respectively. Scintillator imaging output results using a single image stack requiring no postexposure processing (needed for OSLD) or repeat manual measurements (needed for IC). CONCLUSION: Imaging of scintillation light emission from plastic rods is a viable and efficient method for carrying out TBI 60 Co irradiator QA. We have shown that this technique can accurately measure field homogeneity, symmetry, light-radiation field correspondence, and dose rate effects.


Assuntos
Radioisótopos de Cobalto/uso terapêutico , Imagem Óptica , Irradiação Corporal Total/instrumentação , Controle de Qualidade , Radiometria , Dosagem Radioterapêutica
13.
Med Phys ; 46(9): 3998-4009, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31206709

RESUMO

PURPOSE: The incorporation of cone-beam computed tomography (CBCT) has allowed for enhanced image-guided radiation therapy. While CBCT allows for daily 3D imaging, images suffer from severe artifacts, limiting the clinical potential of CBCT. In this work, a deep learning-based method for generating high quality corrected CBCT (CCBCT) images is proposed. METHODS: The proposed method integrates a residual block concept into a cycle-consistent adversarial network (cycle-GAN) framework, called res-cycle GAN, to learn a mapping between CBCT images and paired planning CT images. Compared with a GAN, a cycle-GAN includes an inverse transformation from CBCT to CT images, which constrains the model by forcing calculation of both a CCBCT and a synthetic CBCT. A fully convolution neural network with residual blocks is used in the generator to enable end-to-end CBCT-to-CT transformations. The proposed algorithm was evaluated using 24 sets of patient data in the brain and 20 sets of patient data in the pelvis. The mean absolute error (MAE), peak signal-to-noise ratio (PSNR), normalized cross-correlation (NCC) indices, and spatial non-uniformity (SNU) were used to quantify the correction accuracy of the proposed algorithm. The proposed method is compared to both a conventional scatter correction and another machine learning-based CBCT correction method. RESULTS: Overall, the MAE, PSNR, NCC, and SNU were 13.0 HU, 37.5 dB, 0.99, and 0.05 in the brain, 16.1 HU, 30.7 dB, 0.98, and 0.09 in the pelvis for the proposed method, improvements of 45%, 16%, 1%, and 93% in the brain, and 71%, 38%, 2%, and 65% in the pelvis, over the CBCT image. The proposed method showed superior image quality as compared to the scatter correction method, reducing noise and artifact severity. The proposed method produced images with less noise and artifacts than the comparison machine learning-based method. CONCLUSIONS: The authors have developed a novel deep learning-based method to generate high-quality corrected CBCT images. The proposed method increases onboard CBCT image quality, making it comparable to that of the planning CT. With further evaluation and clinical implementation, this method could lead to quantitative adaptive radiation therapy.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Razão Sinal-Ruído
14.
Phys Med Biol ; 64(6): 065022, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30561373

RESUMO

In proton therapy, range uncertainties induced by the conversion from x-ray CT (xCT) Hounsfield units (HU) to relative stopping power (RSP) compromise the precision of dose delivery. To reduce range uncertainties induced by HU-converted RSPs, this study investigates optimizing the RSP of individual voxels in xCT iteratively based on multi-projection proton radiography (pRG) acquired using a single amorphous silicon flat panel imager. Time-resolved dose rate functions (DRF) were measured by the imager placed downstream of a test phantom consisting of tissue substitute materials. Water equivalent path lengths (WEPL) in the pRG were derived. By rotating the phantom, multiple pRG projections were acquired at angles from 0 to 358° with an increment of 2°. X-ray CT of the phantom was acquired and co-registered with the pRG acquisition coordinates. RSPs of individual xCT voxels were optimized iteratively by minimizing the difference between the measured WEPLs and the calculated WEPLs by ray tracing with HU-converted RSPs. Pixels in pRGs that exhibited severe proton range mixing were rejected for the optimization. Tikhonov regularization was applied under the assumption that HU-converted RSPs are inaccurate, but the inaccuracy is within a few percent. While ~50% of WEPL pixels were rejected due to severe range mixing in pRG, RSPs of >90% CT voxels could still be optimized if multiple pRG projections, e.g. ⩾12, around the phantom are utilized. For tissue substitute materials in a cylindrical phantom, percentage errors of RSPs were reduced from a range of -8% to +4% to be within ±2%. Further optimization, achieved by implementing a material-specific regularization parameter, reduced percent errors to be within ±0.5%. This study demonstrates the concept of optimizing RSPs of individual CT voxels with multi-projection pRGs acquired by a single flat panel imager, which could be further explored and implemented in proton therapy to reduce range uncertainties.


Assuntos
Algoritmos , Imagens de Fantasmas , Terapia com Prótons , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normas , Humanos
15.
Nat Biomed Eng ; 2(4): 254-264, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30899599

RESUMO

Low signal-to-noise ratios and limited imaging depths restrict the ability of optical-imaging modalities to detect and accurately quantify molecular emissions from tissue. Here, by using a scanning external X-ray beam from a clinical linear accelerator to induce Cherenkov excitation of luminescence in tissue, we demonstrate in vivo mapping of the oxygenation of tumours at depths of several millimetres, with submillimetre resolution and nanomolar sensitivity. This was achieved by scanning thin sheets of the X-ray beam orthogonally to the emission-detection plane, and by detecting the signal via a time-gated CCD camera synchronized to the radiation pulse. We also show with experiments using phantoms and with simulations that the performance of Cherenkov-excited luminescence scanned imaging (CELSI) is limited by beam size, scan geometry, probe concentration, radiation dose and tissue depth. CELSI might provide the highest sensitivity and resolution in the optical imaging of molecular tracers in vivo.

16.
Med Phys ; 45(1): 48-59, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29134674

RESUMO

PURPOSE: The purpose of this work is to evaluate the performance of dual-energy CT (DECT) for determining proton stopping power ratios (SPRs) in an experimental environment and to demonstrate its potential advantages over conventional single-energy CT (SECT) in clinical conditions. METHODS: Water equivalent range (WER) measurements of 12 tissue-equivalent plastic materials and 12 fresh animal tissue samples are performed in a 195 MeV broad proton beam using the dose extinction method. SECT and DECT scans of the samples are performed with a dual-source CT scanner (Siemens SOMATOM Definition Flash). The methods of Schneider et al. (1996), Bourque et al. (2014), and Lalonde et al. (2017) are used to predict proton SPR on SECT and DECT images. From predicted SPR values, the WER of the proton beam through the sample is predicted for SECT and DECT using Monte Carlo simulations and compared to the measured WER. RESULTS: For homogeneous tissue-equivalent plastic materials, results with DECT are consistent with experimental measurements and show a systematic reduction of SPR uncertainty compared to SECT, with root-mean-square errors of 1.59% versus 0.61% for SECT and DECT, respectively. Measurements with heterogeneous animal samples show a clear reduction of the bias on range predictions in the presence of bones, with -0.88% for SECT versus -0.58% and -0.14% for both DECT methods. An uncertainty budget allows isolating the effect of CT number conversion to SPR and predicts improvements by DECT over SECT consistently with theoretical predictions, with 0.34% and 0.31% for soft tissues and bones in the experimental setup compared to 0.34% and 1.14% with the theoretical method. CONCLUSIONS: The present work uses experimental measurements in a realistic clinical environment to show potential benefits of DECT for proton therapy treatment planning. Our results show clear improvements over SECT in tissue-equivalent plastic materials and animal tissues. Further work towards using Monte Carlo simulations for treatment planning with DECT data and a more detailed investigation of the uncertainties on I-value and limitations on the Bragg additivity rule could potentially further enhance the benefits of this imaging technology for proton therapy.


Assuntos
Terapia com Prótons , Radioterapia Guiada por Imagem , Tomografia Computadorizada por Raios X/métodos , Método de Monte Carlo , Radiometria , Dosagem Radioterapêutica
17.
Phys Med Biol ; 63(1): 015030, 2017 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-29116055

RESUMO

Proton radiography, which images patients with the same type of particles as those with which they are to be treated, is a promising approach to image guidance and water equivalent path length (WEPL) verification in proton radiation therapy. We have shown recently that proton radiographs could be obtained by measuring time-resolved dose rate functions (DRFs) using an x-ray amorphous silicon flat panel. The WEPL values were derived solely from the root-mean-square (RMS) of DRFs, while the intensity information in the DRFs was filtered out. In this work, we explored the use of such intensity information for potential improvement in WEPL accuracy and imaging quality. Three WEPL derivation methods based on, respectively, the RMS only, the intensity only, and the intensity-weighted RMS were tested and compared in terms of the quality of obtained radiograph images and the accuracy of WEPL values. A Gammex CT calibration phantom containing inserts made of various tissue substitute materials with independently measured relative stopping powers (RSP) was used to assess the imaging performances. Improved image quality with enhanced interfaces was achieved while preserving the accuracy by using intensity information in the calibration. Other objects, including an anthropomorphic head phantom, a proton therapy range compensator, a frozen lamb's head and an 'image quality phantom' were also imaged. Both the RMS only and the intensity-weighted RMS methods derived RSPs within ± 1% for most of the Gammex phantom inserts, with a mean absolute percentage error of 0.66% for all inserts. In the case of the insert with a titanium rod, the method based on RMS completely failed, whereas that based on the intensity-weighted RMS was qualitatively valid. The use of intensity greatly enhanced the interfaces between different materials in the obtained WEPL images, suggesting the potential for image guidance in areas such as patient positioning and tumor tracking by proton radiography.


Assuntos
Cabeça/diagnóstico por imagem , Imagens de Fantasmas , Prótons , Radiografia/métodos , Tomografia Computadorizada por Raios X/métodos , Animais , Calibragem , Doses de Radiação , Radiografia/instrumentação , Radiografia/normas , Ovinos
18.
Phys Med Biol ; 62(14): 5640-5651, 2017 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-28644820

RESUMO

For proton therapy, an accurate conversion of CT HU to relative stopping power (RSP) is essential. Validation of the conversion based on real tissue samples is more direct than the current practice solely based on tissue substitutes and can potentially address variations over the population. Based on a novel dose extinction method, we measured water equivalent path lengths (WEPL) on animal tissue samples to evaluate the accuracy of CT HU to RSP conversion and potential variations over a population. A broad proton beam delivered a spread out Bragg peak to the samples sandwiched between a water tank and a 2D ion-chamber detector. WEPLs of the samples were determined from the transmission dose profiles measured as a function of the water level in the tank. Tissue substitute inserts and Lucite blocks with known WEPLs were used to validate the accuracy. A large number of real tissue samples were measured. Variations of WEPL over different batches of tissue samples were also investigated. The measured WEPLs were compared with those computed from CT scans with the Stoichiometric calibration method. WEPLs were determined within ±0.5% percentage deviation (% std/mean) and ±0.5% error for most of the tissue surrogate inserts and the calibration blocks. For biological tissue samples, percentage deviations were within ±0.3%. No considerable difference (<1%) in WEPL was observed for the same type of tissue from different sources. The differences between measured WEPLs and those calculated from CT were within 1%, except for some bony tissues. Depending on the sample size, each dose extinction measurement took around 5 min to produce ~1000 WEPL values to be compared with calculations. This dose extinction system measures WEPL efficiently and accurately, which allows the validation of CT HU to RSP conversions based on the WEPL measured for a large number of samples and real tissues.


Assuntos
Terapia com Prótons/métodos , Doses de Radiação , Água , Calibragem , Radiometria , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X
19.
J Biophotonics ; 10(5): 645-656, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27507213

RESUMO

This study's goal was to determine how Cherenkov radiation emission observed in radiotherapy is affected by predictable factors expected in patient imaging. Factors such as tissue optical properties, radiation beam properties, thickness of tissues, entrance/exit geometry, curved surface effects, curvature and imaging angles were investigated through Monte Carlo simulations. The largest physical cause of variation of the correlation ratio between of Cherenkov emission and dose was the entrance/exit geometry (˜50%). The largest human tissue effect was from different optical properties (˜45%). Beyond these, clinical beam energy varies the correlation ratio significantly (˜20% for X-ray beams), followed by curved surfaces (˜15% for X-ray beams and ˜8% for electron beams), and finally, the effect of field size (˜5% for X-ray beams). Other investigated factors which caused variations less than 5% were tissue thicknesses and source to surface distance. The effect of non-Lambertian emission was negligible for imaging angles smaller than 60 degrees. The spectrum of Cherenkov emission tends to blue-shift along the curved surface. A simple normalization approach based on the reflectance image was experimentally validated by imaging a range of tissue phantoms, as a first order correction for different tissue optical properties.


Assuntos
Radiometria/métodos , Radioterapia , Humanos , Método de Monte Carlo , Fenômenos Ópticos , Imagens de Fantasmas
20.
Phys Med Biol ; 61(10): 3955-68, 2016 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-27120085

RESUMO

Ionizing radiation delivered by a medical linear accelerator (LINAC) generates Cherenkov emission within the treated tissue. A fraction of this light, in the 600-900 nm wavelength region, propagates through centimeters of tissue and can be used to excite optical probes in vivo, enabling molecular sensing of tissue analytes. The success of isolating the emission signal from this Cherenkov excitation background is dependent on key factors such as: (i) the Stokes shift of the probe spectra; (ii) the excited state lifetime; (iii) the probe concentration; (iv) the depth below the tissue surface; and (v) the radiation dose used. Previous studies have exclusively focused on imaging phosphorescent dyes, rather than fluorescent dyes. However there are only a few biologically important phosphorescent dyes and yet in comparison there are thousands of biologically relevant fluorescent dyes. So in this study the focus was a study of efficacy of Cherenkov-excited luminescence using fluorescent commercial near-infrared probes, IRDye 680RD, IRDye 700DX, and IRDye 800CW, and comparing them to the well characterized phosphorescent probe Oxyphor PtG4, an oxygen sensitive dye. Each probe was excited by Cherenkov light from a 6 MV external radiation beam, and measured in continuous wave or time-gated modes. The detection was performed by spectrally resolving the luminescence signals, and measuring them with spectrometer-based separation on an ICCD detector. The results demonstrate that IRDye 700DX and PtG4 allowed for the maximal signal to noise ratio. In the case of the phosphorescent probe, PtG4, with emission decays on the microsecond (µs) time scale, time-gated acquisition was possible, and it allowed for higher efficacy in terms of the probe concentration and detection depth. Phantoms containing the probe at 5 mm depth could be detected at concentrations down to the nanoMolar range, and at depths into the tissue simulating phantom near 3 cm. In vivo studies showed that 5 nmol of dye was readily detected with radiation doses less than 5 cGy. Since concentration, radiation dose and depth each contribute to the level of the detected signal, it may be possible to improve any of these parameters at expense of the others. This paradigm of nanoMolar sensitivity for optical reporters in vivo introduces the concept of molecular sensing of tumors during therapy or diagnostically with biologically relevant concentrations of fluorescent reporters.


Assuntos
Fluorescência , Doses de Radiação , Monitoramento de Radiação/métodos , Elétrons , Humanos , Aceleradores de Partículas , Imagens de Fantasmas , Monitoramento de Radiação/instrumentação , Raios X
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