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

3.
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.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33227443

RESUMO

PURPOSE: The value of Cherenkov imaging as an on-patient, real-time, treatment delivery verification system was examined in a 64-patient cohort during routine radiation treatments in a single-center study. METHODS & MATERIALS: Cherenkov cameras were mounted in treatment rooms and used to image patients during their standard radiotherapy regimen for various sites, predominantly for whole breast and total skin electron therapy. For most patients, multiple fractions were imaged, with some involving bolus or scintillators on the skin. Measures of repeatability were calculated with a mean distance to conformity (MDC) for breast irradiation images. RESULTS: In breast treatments, Cherenkov images identified fractions when treatment delivery resulted in dose on the contralateral breast, the arm, or chin, and found non-ideal bolus positioning. In sarcoma treatments, safe positioning of the contralateral leg was monitored. For all 199 imaged breast treatment fields, the inter-fraction MDC was within 7 mm as compared to the first day of treatment (with only 7.5% of treatments exceeding 3 mm), and all but one fell within 7 mm relative to the treatment plan. The value of imaging dose through clear bolus or quantifying surface dose with scintillator dots was examined. Cherenkov imaging also was able to assess field match lines in cerebral-spinal (CSI) and breast irradiation with nodes. Treatment imaging of other anatomical sites confirmed the value of surface dose imaging more broadly. CONCLUSIONS: Daily radiotherapy can be imaged routinely via Cherenkov emissions. Both the real-time images and the post-treatment, cumulative images provide surrogate maps of surface dose delivery that can be used for incident discovery and/or continuous improvement in many delivery techniques. In this initial 64-patient cohort, we discovered six minor incidents using Cherenkov imaging, without which, would have gone undetected. In addition, imaging provides automated, quantitative metrics useful to determining the quality of radiotherapy delivery.

5.
Opt Lett ; 45(22): 6130-6133, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33186932

RESUMO

Cherenkov light induced from megavolt (MV) X-rays during external beam radiotherapy serves as an internal light source to excite phosphors or fluorophores within biological tissues for molecular imaging. The broad spectrum of Cherenkov light leads to significant spectral overlap with any luminescence emission and, to overcome this problem, a single pixel hyperspectral imaging methodology was demonstrated here by coupling the detection with light sheet scanning and filtered back projection reconstruction of hyperspectral images. Thin scanned sheets of MV X-rays produce Cherenkov light to illuminate the planes deep within the tissue-simulating media. A fluorescence probe was excited by Cherenkov light, and a complete hyperspectral sinogram of the data was obtained through translation and rotation of the beam. Hyperspectral 2D images finally were reconstructed. Through this approach of spectral unmixing, it was possible to resolve hyperspectral images of both the Cherenkov and resulting fluorescence intensity from molecular sensors.

6.
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.

7.
J Biomed Opt ; 25(11)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33236619

RESUMO

SIGNIFICANCE: The necessity to use exogenous probes for optical oxygen measurements in radiotherapy poses challenges for clinical applications. Options for implantable probe biotechnology need to be improved to alleviate toxicity concerns in human use and facilitate translation to clinical trial use. AIM: To develop an implantable oxygen sensor containing a phosphorescent oxygen probe such that the overall administered dose of the probe would be below the Federal Drug Administration (FDA)-prescribed microdose level, and the sensor would provide local high-intensity signal for longitudinal measurements of tissue pO2. APPROACH: PtG4, an oxygen quenched dendritic molecule, was mixed into an agarose matrix at 100 µM concentration, allowing for local injection into tumors at the total dose of 10 nmol per animal, forming a gel at the site of injection. Cherenkov-excited luminescence imaging (CELI) was used to acquire the phosphorescence and provide intratumoral pO2. RESULTS: Although PtG4 does not form covalent bonds with agarose and gradually leaches out into the surrounding tissue, its retention time within the gel was sufficiently long to demonstrate the capability to measure intratumoral pO2 with the implantable gel sensors. The sensor's performance was first evaluated in vitro in tissue simulation phantoms, and then the sensor was used to measure changes in oxygen in MDA-MB-231 tumors during hypofractionated radiotherapy. CONCLUSIONS: Our study demonstrates that implantable oxygen sensors in combination with CELI present a promising approach for quantifying oxygen changes during the course of radiation therapy and thus for evaluating the tumor response to radiation. By improving the design of the gel-probe composition in order to prevent leaching of the probe into the tissue, biosensors can be created that should allow longitudinal oxygen measurements in tumors by means of CELI while using FDA-compliant microdose levels of the probe and thus lowering toxicity concerns.

8.
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.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33002542

RESUMO

PURPOSE: The extreme microscopic heterogeneity of tumors makes it difficult to characterize tumor hypoxia. We evaluated how changes in the spatial resolution of oxygen imaging could alter measures of tumor hypoxia and their correlation to radiation therapy response. METHODS AND MATERIALS: Cherenkov-Excited Luminescence Imaging (CELI) in combination with an oxygen probe, Oxyphor PtG4 was used to directly image tumor pO2 distributions with 0.2 mm spatial resolution at the time of radiation delivery. These pO2 images were analyzed with variations of reduced spatial resolution from 0.2 mm to 5 mm, to investigate the influence of how reduced imaging spatial resolution would affect the observed tumor hypoxia. As an in vivo validation test, mice bearing tumor xenografts were imaged for hypoxic fraction and median pO2 to examine the predictive link with tumor response to radiation therapy, while accounting for spatial resolution. RESULTS: In transitioning from voxel sizes of 200 µm to 3mm, the median pO2 values increased by a few mmHg, while the hypoxic fraction decreased by more than 50%. When looking at radiation-responsive tumors, the median pO2 values changed just a few mmHg as a result of treatment, while the hypoxic fractions changed by as much as 50%. This latter change, however, could only be seen when sampling was performed with high spatial resolution. Median pO2 or similar quantities obtained from low resolution measurements are commonly used in clinical practice, however these parameters are much less sensitive to changes in the tumor microenvironment than the tumor hypoxic fraction obtained from high-resolution oxygen images. CONCLUSIONS: This study supports the hypothesis that for adequate measurements of the tumor response to radiation therapy, oxygen imaging with high spatial resolution is required in order to accurately characterize the hypoxic fraction.

10.
Opt Lett ; 45(13): 3761-3764, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32630948

RESUMO

Fluorescence imaging is severely limited by the background and autofluorescence of tissues for in vivo detection of circulating tumor cells (CTCs). Time-gated luminescence (TGL) imaging, in combination with luminescent probes that possess hundreds of microsecond emission lifetimes, can be used to effectively suppress this background, which has predominantly nanosecond lifetimes. This Letter demonstrates the feasibility of TGL imaging using luminescent probes for the in vivo real time imaging and tracking of single CTCs circulating freely in the blood vessels with higher accuracy given by substantially higher signal-to-noise ratio. The luminescent probe used in this Letter was a commercial Eu3+ chelate (EuC) nanosphere with a super-long lifetime of near 800 µs, which enabled TGL imaging to achieve background-free detection with ∼5 times higher SNR versus steady state. Phantom and in vivo mouse studies indicated that EuC labeled tumor cells moving in medium or bloodstream at the speed of 1-2 mm/s could be captured in real time.

11.
J Med Imaging (Bellingham) ; 7(3): 034002, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32509916

RESUMO

Purpose: Quality assurance (QA) of dose homogeneity in total skin electron therapy (TSET) is challenging since each patient is positioned in six standing poses with two beam angles. Our study tested the feasibility of a unique approach for TSET QA through computational display of the cumulative dose, constructed and synthesized by computer animation methods. Approach: Dose distributions from Cherenkov emission images were projected onto a scanned 3D body model. Topographically mapped surfaces of the patient were recorded in each of six different delivery positions, while a Cherenkov camera acquired images. Computer animation methods allowed a fitted 3D human body model of the patient to be created with deformation of the limbs and torso to each position. A two-dimensional skin map was extracted from the 3D model of the full surface of the patient. This allowed the dose mapping to be additively accumulated independent of body position, with the total dose summed in a 2D map and reinterpreted on the 3D body display. Results: For the body model, the mean Hausdorff error distance was below 2 cm, setting the spatial accuracy limit. The dose distribution over the patient's 3D model generally matched the Cherenkov/dose images. The dose distribution mapping was estimated to be near 1.5 cm accuracy based upon a phantom study. The body model must most closely match at the edges of the mesh to ensure that high dose gradients are not projected onto the wrong location. Otherwise 2 to 3 cm level errors in positioning in the mesh do not appear to cause larger than 5% dose errors. The cumulative dose images showed regions of overlap laterally and regions of low intensity in the posterior arms. Conclusions: The proposed modeling and animation can be used to visualize and analyze the accumulated dose in TSET via display of the summed dose/Cherenkov images on a single body surface.

12.
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.

13.
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
14.
J Appl Clin Med Phys ; 21(6): 158-162, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32306551

RESUMO

PURPOSE: The novel scintillator-based system described in this study is capable of accurately and remotely measuring surface dose during Total Skin Electron Therapy (TSET); this dosimeter does not require post-exposure processing or annealing and has been shown to be re-usable, resistant to radiation damage, have minimal impact on surface dose, and reduce chances of operator error compared to existing technologies e.g. optically stimulated luminescence detector (OSLD). The purpose of this study was to quantitatively analyze the workflow required to measure surface dose using this new scintillator dosimeter and compare it to that of standard OSLDs. METHODS: Disc-shaped scintillators were attached to a flat-faced phantom and a patient undergoing TSET. Light emission from these plastic discs was captured using a time-gated, intensified, camera during irradiation and converted to dose using an external calibration factor. Time required to complete each step (daily QA, dosimeter preparation, attachment, removal, registration, and readout) of the scintillator and OSLD surface dosimetry workflows was tracked. RESULTS: In phantoms, scintillators and OSLDs surface doses agreed within 3% for all data points. During patient imaging it was found that surface dose measured by OSLD and scintillator agreed within 5% and 3% for 35/35 and 32/35 dosimetry sites, respectively. The end-to-end time required to measure surface dose during phantom experiments for a single dosimeter was 78 and 202 sec for scintillator and OSL dosimeters, respectively. During patient treatment, surface dose was assessed at 7 different body locations by scintillator and OSL dosimeters in 386 and 754 sec, respectively. CONCLUSION: Scintillators have been shown to report dose nearly twice as fast as OSLDs with substantially less manual work and reduced chances of human error. Scintillator dose measurements are automatically saved to an electronic patient file and images contain a permanent record of the dose delivered during treatment.

15.
Opt Lett ; 45(3): 664, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32004278

RESUMO

This publisher's note contains corrections to Opt. Lett.45, 284 (2020)OPLEDP0146-959210.1364/OL.45.000284.

16.
Nat Commun ; 11(1): 573, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996677

RESUMO

Hypoxia in solid tumors is thought to be an important factor in resistance to therapy, but the extreme microscopic heterogeneity of the partial pressures of oxygen (pO2) between the capillaries makes it difficult to characterize the scope of this phenomenon without invasive sampling of oxygen distributions throughout the tissue. Here we develop a non-invasive method to track spatial oxygen distributions in tumors during fractionated radiotherapy, using oxygen-dependent quenching of phosphorescence, oxygen probe Oxyphor PtG4 and the radiotherapy-induced Cherenkov light to excite and image the phosphorescence lifetimes within the tissue. Mice bearing MDA-MB-231 breast cancer and FaDu head neck cancer xenografts show different pO2 responses during each of the 5 fractions (5 Gy per fraction), delivered from a clinical linear accelerator. This study demonstrates subsurface in vivo mapping of tumor pO2 distributions with submillimeter spatial resolution, thus providing a methodology to track response of tumors to fractionated radiotherapy.


Assuntos
Fracionamento da Dose de Radiação , Processamento de Imagem Assistida por Computador/métodos , Oxigênio/química , Radioterapia/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Engenharia Biomédica/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Linhagem Celular Tumoral , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Xenoenxertos , Humanos , Hipóxia , Metaloporfirinas , Camundongos , Pressão Parcial , Aceleradores de Partículas
17.
Med Phys ; 47(1): 201-212, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31665544

RESUMO

BACKGROUND: Total skin electron therapy (TSET) utilizes high-energy electrons to treat malignancies on the entire body surface. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interactions between the high-energy electron beam and tissue. METHODS AND MATERIALS: With a time-gated intensified camera system, the Cherenkov emission can be used to evaluate the dose uniformity on the surface of the patient in real time. Fifteen patients undergoing TSET in various conditions (whole body and half body) were imaged and analyzed. Each patient was monitored during TSET via in vivo detectors (IVD) in nine locations. For accurate Cherenkov imaging, a comparison between IVD and Cherenkov profiles was conducted using a polyvinyl chloride board to establish the perspective corrections. RESULTS AND DISCUSSION: With proper corrections developed in this study including the perspective and inverse square corrections, the Cherenkov imaging provided two-dimensional maps proportional to dose and projected on patient skin. The results of ratio between chest and umbilicus points were in good agreement with in vivo point dose measurements, with a standard deviation of 2.4% compared to OSLD measurements. CONCLUSIONS: Cherenkov imaging is a viable tool for validating patient-specific dose distributions during TSET.


Assuntos
Elétrons/uso terapêutico , Imagem Óptica , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica
18.
Int J Radiat Oncol Biol Phys ; 106(2): 422-429, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669563

RESUMO

PURPOSE: Patients have reported sensations of seeing light flashes during radiation therapy, even with their eyes closed. These observations have been attributed to either direct excitation of retinal pigments or generation of Cherenkov light inside the eye. Both in vivo human and ex vivo animal eye imaging was used to confirm light intensity and spectra to determine its origin and overall observability. METHODS AND MATERIALS: A time-gated and intensified camera was used to capture light exiting the eye of a patient undergoing stereotactic radiosurgery in real time, thereby verifying the detectability of light through the pupil. These data were compared with follow-up mechanistic imaging of ex vivo animal eyes with thin radiation beams to evaluate emission spectra and signal intensity variation with anatomic depth. Angular dependency of light emission from the eye was also measured. RESULTS: Patient imaging showed that light generation in the eye during radiation therapy can be captured with a signal-to-noise ratio of 68. Irradiation of ex vivo eye samples confirmed that the spectrum matched that of Cherenkov emission and that signal intensity was largely homogeneous throughout the entire eye, from the cornea to the retina, with a slight maximum near 10 mm depth. Observation of the signal external to the eye was possible through the pupil from 0° to 90°, with a detected emission near 2500 photons per millisecond (during peak emission of the ON cycle of the pulsed delivery), which is over 2 orders of magnitude higher than the visible detection threshold. CONCLUSIONS: By quantifying the spectra and magnitude of the signal, we now have direct experimental observations that Cherenkov light is generated in the eye during radiation therapy and can contribute to perceived light flashes. Furthermore, this technique can be used to further study and measure phosphenes in the radiation therapy clinic.


Assuntos
Luz , Fenômenos Fisiológicos Oculares/efeitos da radiação , Radiocirurgia , Razão Sinal-Ruído , Animais , Humanos , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Pupila/fisiologia , Suínos
19.
Med Phys ; 47(3): 1258-1267, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31821573

RESUMO

PURPOSE: Treatment planning systems (TPSs) for MR-linacs must employ Monte Carlo-based simulations of dose deposition to model the effects of the primary magnetic field on dose. However, the accuracy of these simulations, especially for areas of tissue-air interfaces where the electron return effect (ERE) is expected, is difficult to validate due to physical constraints and magnetic field compatibility of available detectors. This study employs a novel dosimetric method based on remotely captured, real-time optical Cherenkov and scintillation imaging to visualize and quantify the ERE. METHODS: An intensified CMOS camera was used to image two phantoms with designed ERE cavities. Phantom A was a 40 cm × 10 cm × 10 cm clear acrylic block drilled with five holes of increasing diameters (0.5, 1, 2, 3, 4 cm). Phantom B was a clear acrylic block (25 cm × 20 cm × 5 cm) with three cavities of increasing diameter (3, 2, 1 cm) split into two halves in the transverse plane to accommodate radiochromic film. Both phantoms were imaged while being irradiated by 6 MV flattening filter free (FFF) beams within a MRIdian Viewray (Viewray, Cleveland, OH) MR-linac (0.34 T primary field). Phantom A was imaged while being irradiated by 6 MV FFF beams on a conventional linac (TrueBeam, Varian Medical Systems, San Jose, CA) to serve as a control. Images were post processed in Matlab (Mathworks Inc., Natick, MA) and compared to TPS dose volumes. RESULTS: Control imaging of Phantom A without the presence of a magnetic field supports the validity of the optical image data to a depth of 6 cm. In the presence of the magnetic field, the optical data shows deviations from the commissioned TPS dose in both intensity and localization. The largest air cavity examined (3 cm) indicated the largest dose differences, which were above 20% at some locations. Experiments with Phantom B illustrated similar agreement between optical and film dosimetry comparisons with TPS data in areas not affected by ERE. CONCLUSION: There are some appreciable differences in dose intensity and spatial dose distribution observed between the novel experimental data set and the dose models produced by the current clinically implemented MR-IGRT TPS.

20.
Med Phys ; 46(11): 5227-5237, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31472093

RESUMO

PURPOSE: We demonstrate the feasibility of optical imaging as a quality assurance tool for static small beamlets, and pretreatment verification tool for radiosurgery and volumetric-modulated arc therapy (VMAT) plans. METHODS: Small static beams and clinical VMAT plans were simulated in a treatment planning system (TPS) and delivered to a cylindrical tank filled with water-based liquid scintillator. Emission was imaged using a blue-sensitive, intensified CMOS camera time-gated to the linac pulses. For static beams, percentage depth and cross beam profiles of projected intensity distribution were compared to TPS data. Two-dimensional (2D) gamma analysis was performed on all clinical plans, and the technique was tested for sensitivity against common errors (multileaf collimator position, gantry angle) by inducing deliberate errors in the VMAT plans control points. The technique's detection limits for spatial resolution and the smallest number of control points that could be imaged reliably were also tested. The sensitivity to common delivery errors was also compared against a commercial 2.5D diode array dosimeter. RESULTS: A spatial resolution of 1 mm was achieved with our imaging setup. The optical projected percentage depth intensity profiles agreed to within 2% relative to the TPS data for small static square beams (5, 10, and 50 mm2 ). For projected cross beam profiles, a gamma pass rate >99% was achieved for a 3%/1 mm criteria. All clinical plans passed the 3%/3 mm criteria with >95% passing rate. A static 5 mm beam with 20 Monitor Units could be measured with an average percent difference of 5.5 ± 3% relative to the TPS. The technique was sensitive to multileaf collimator errors down to 1 mm and gantry angle errors of 1°. CONCLUSIONS: Optical imaging provides ample spatial resolution for imaging small beams. The ability to faithfully image down to 20 MU of 5 mm, 6 MV beamlets prove the ability to perform quality assurance for each control point within dynamic plans. The technique is sensitive to small offset errors in gantry angles and multileaf collimator (MLC) leaf positions, and at certain scenario, it exhibits higher sensitivity than a commercial 2.5D diode array.


Assuntos
Imagem Óptica , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada , Dosimetria Fotográfica , Humanos , Razão Sinal-Ruído , Fatores de Tempo
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