Three-Dimensional Printing for Construction of Tissue-Equivalent Anthropomorphic Phantoms and Determination of Conceptus Dose.

OBJECTIVE: The purpose of this study was to develop a road map for rapid construction of anthropomorphic phantoms from computational human phantoms for use in diagnostic imaging dosimetry studies. These phantoms are ideal for performing pregnant-patient dosimetry because the phantoms imitate the size and attenuation properties of an average-sized pregnant woman for multiple gestational periods. MATERIALS AND METHODS: The method was derived from methods and materials previously described but adapted for 3D printing technology. A 3D printer was used to transform computational models into a physical duplicate with small losses in spatial accuracy and to generate tissue-equivalent materials characterized for diagnostic energy x-rays. A series of pregnant abdomens were selected as prototypes because of their large size and complex modeling. The process involved the following steps: segmentation of anatomy used for modeling; transformation of the computational model into a printing file format; preparation, characterization, and introduction of phantom materials; and model removal and phantom assembly. RESULTS: The density of the homogenized soft tissue-equivalent substitute was optimized by combining 9.0% by weight of urethane filler powder and 91.0% urethane polymer, which resulted in a mean density of 1.041 g/cm3 measured over 20 samples. Density varied among all of the samples by 0.0026 g/cm3. The total variation in density was 0.00261 g/cm3. The half-value layer of the bone material was measured to be 1.7 mm of bone material at 120 kVp and when simulated by use of the density of the bone tissue-equivalent substitute (1.60 g/cm3) was determined to be 1.61 mm of bone tissue. For dosimetry purposes the phantom provided excellent results for evaluating a site's protocol based on scan range. CONCLUSION: The 3D printing technology is applicable to the fabrication of phantoms used for performing dosimetry. The tissue-equivalent materials used to substitute for the soft tissue were developed to be highly adaptable for optimization based on the dosimetry application. Use of this method resulted in more automated phantom construction with decreased construction time and increased out-of-slice spatial resolution of the phantoms.

Commissioning of the world's first compact pencil-beam scanning proton therapy system.

This paper summarizes clinical commissioning of the world's first commercial, clinically utilized installation of a compact, image-guided, pencil-beam scanning, intensity-modulated proton therapy system, the IBA Proteus® ONE, at the Willis-Knighton Cancer Center (WKCC) in Shreveport, LA. The Proteus® ONE is a single-room, compact-gantry system employing a cyclotron-generated proton beam with image guidance via cone-beam CT as well as stereoscopic orthogonal and oblique planar kV imaging. Coupling 220° of gantry rotation with a 6D robotic couch capable of in plane patient rotations of over 180° degrees allows for 360° of treatment access. Along with general machine characterization, system commissioning required: (a) characterization and calibration of the proton beam, (b) treatment planning system commissioning including CT-to-density curve determination, (c) image guidance system commissioning, and (d) safety verification (interlocks and radiation survey). System readiness for patient treatment was validated by irradiating calibration TLDs as well as prostate, head, and lung phantoms from the Imaging and Radiation Oncology Core (IROC), Houston. These results confirmed safe and accurate machine functionality suitable for patient treatment. WKCC also successfully completed an on-site dosimetry review by an independent team of IROC physicists that corroborated accurate Proteus® ONE dosimetry.

Fetal organ dosimetry for the Techa River and Ozyorsk Offspring Cohorts, part 2: radionuclide S values for fetal self-dose and maternal cross-dose.

One of the many objectives of the European Union's SOLO (Epidemiological Studies of Exposed Southern Urals Populations) project is to quantify the radiation dose-response following chronic in utero exposures to ionizing radiation. The project is presently conducting a pooled analysis of two cohorts of individuals born to exposed mothers-the Techa River Offspring Cohort (TROC) and the Ozyorsk Offspring Cohort (OOC). The TROC includes the offspring of mothers with external exposures to contaminated riverbanks and internal ingestions of (89)Sr, (90)Sr/(90)Y, and (137)Cs/(137m)Ba, while the OOC includes the offspring of mothers with external exposures seen within the Mayak plutonium production facilities and internal inhalation of (239)Pu and possibly (131)I. In the present study, a newly created Urals-based series of fetal and maternal models is employed to assess S values for all seven radionuclides. Among all fetal ages, S values ranged in magnitude from 10(-14) to 10(-10) Gy per Bq-s for fetal source organs and from 10(-18) to 10(-14) Gy per Bq-s from maternal source organs, depending upon particle type, particle energy, and fetal age. For a given radionuclide and fetal age, S values for fetal source organs were approximately two orders of magnitude higher than for maternal source organs. Little variation in S values was observed among fetal source organs, while variations of over 100 % with respect to the mean were observed for maternal source organs near the fetus. S value variations from maternal cross-fire were highly dependent on fetal position and separation distance from the maternal source organ. These radionuclide S values have been coupled with biokinetic models for use in cohort dose assessment within the SOLO project.

Fetal organ dosimetry for the Techa River and Ozyorsk offspring cohorts, part 1: a Urals-based series of fetal computational phantoms.

The European Union's SOLO (Epidemiological Studies of Exposed Southern Urals Populations) project aims to improve understanding of cancer risks associated with chronic in utero radiation exposure. A comprehensive series of hybrid computational fetal phantoms was previously developed at the University of Florida in order to provide the SOLO project with the capability of computationally simulating and quantifying radiation exposures to individual fetal bones and soft tissue organs. To improve harmonization between the SOLO fetal biokinetic models and the computational phantoms, a subset of those phantoms was systematically modified to create a novel series of phantoms matching anatomical data representing Russian fetal biometry in the Southern Urals. Using previously established modeling techniques, eight computational Urals-based phantoms aged 8, 12, 18, 22, 26, 30, 34, and 38 weeks post-conception were constructed to match appropriate age-dependent femur lengths, biparietal diameters, individual bone masses and whole-body masses. Bone and soft tissue organ mass differences between the common ages of the subset of UF phantom series and the Urals-based phantom series illustrated the need for improved understanding of fetal bone densities as a critical parameter of computational phantom development. In anticipation for SOLO radiation dosimetry studies involving the developing fetus and pregnant female, the completed phantom series was successfully converted to a cuboidal voxel format easily interpreted by radiation transport software.

Sodium sulfide selectively induces oxidative stress, DNA damage, and mitochondrial dysfunction and radiosensitizes glioblastoma (GBM) cells.

Glioblastoma (GBM) has a poor prognosis despite intensive treatment with surgery and chemoradiotherapy. Previous studies using dose-escalated radiotherapy have demonstrated improved survival; however, increased rates of radionecrosis have limited its use. Development of radiosensitizers could improve patient outcome. In the present study, we report the use of sodium sulfide (Na2S), a hydrogen sulfide (H2S) donor, to selectively kill GBM cells (T98G and U87) while sparing normal human cerebral microvascular endothelial cells (hCMEC/D3). Na2S also decreased mitochondrial respiration, increased oxidative stress and induced γH2AX foci and oxidative base damage in GBM cells. Since Na2S did not significantly alter T98G capacity to perform non-homologous end-joining or base excision repair, it is possible that GBM cell killing could be attributed to increased damage induction due to enhanced reactive oxygen species production. Interestingly, Na2S enhanced mitochondrial respiration, produced a more reducing environment and did not induce high levels of DNA damage in hCMEC/D3. Taken together, this data suggests involvement of mitochondrial respiration in Na2S toxicity in GBM cells. The fact that survival of LN-18 GBM cells lacking mitochondrial DNA (ρ0) was not altered by Na2S whereas the survival of LN-18 ρ+ cells was compromised supports this conclusion. When cells were treated with Na2S and photon or proton radiation, GBM cell killing was enhanced, which opens the possibility of H2S being a radiosensitizer. Therefore, this study provides the first evidence that H2S donors could be used in GBM therapy to potentiate radiation-induced killing.

Comparison of methods for individualized astronaut organ dosimetry: Morphometry-based phantom library versus body contour autoscaling of a reference phantom.

One of the hazards faced by space crew members in low-Earth orbit or in deep space is exposure to ionizing radiation. It has been shown previously that while differences in organ-specific and whole-body risk estimates due to body size variations are small for highly-penetrating galactic cosmic rays, large differences in these quantities can result from exposure to shorter-range trapped proton or solar particle event radiations. For this reason, it is desirable to use morphometrically accurate computational phantoms representing each astronaut for a risk analysis, especially in the case of a solar particle event. An algorithm was developed to automatically sculpt and scale the UF adult male and adult female hybrid reference phantom to the individual outer body contour of a given astronaut. This process begins with the creation of a laser-measured polygon mesh model of the astronaut's body contour. Using the auto-scaling program and selecting several anatomical landmarks, the UF adult male or female phantom is adjusted to match the laser-measured outer body contour of the astronaut. A dosimetry comparison study was conducted to compare the organ dose accuracy of both the autoscaled phantom and that based upon a height-weight matched phantom from the UF/NCI Computational Phantom Library. Monte Carlo methods were used to simulate the environment of the August 1972 and February 1956 solar particle events. Using a series of individual-specific voxel phantoms as a local benchmark standard, autoscaled phantom organ dose estimates were shown to provide a 1% and 10% improvement in organ dose accuracy for a population of females and males, respectively, as compared to organ doses derived from height-weight matched phantoms from the UF/NCI Computational Phantom Library. In addition, this slight improvement in organ dose accuracy from the autoscaled phantoms is accompanied by reduced computer storage requirements and a more rapid method for individualized phantom generation when compared to the UF/NCI Computational Phantom Library.

Organ Doses to Airline Passengers Screened by X-Ray Backscatter Imaging Systems.

Advanced imaging technologies (AIT) are being developed for passenger airline transportation. They are designed to provide enhanced security benefits by identifying objects on passengers that would not be detected by methodologies now used for routine surveillance. X-ray backscatter imaging is one AIT system being considered. Since this technology is based on scanning passengers with ionizing radiation, concern has been raised relating to the health risks associated with these exposures. Recommendations for standards of radiation safety have been proposed by the American National Standards Institute published in ANSI/HPS N43.17-2009. A Monte Carlo based methodology for estimating organ doses received from an X-ray backscatter AIT system is presented. Radiological properties of a reference scanner including beam intensity, geometry and energy spectra were modeled based on previous studies and physical measurements. These parameters were incorporated into a Monte Carlo source subroutine and validated with comparison of simulated versus measured data. One extension of this study was to calculate organ and effective dose on a wide range of potential passengers. Computational phantoms with realistic morphologies were used including adults of 5th, 25th, 50th, 75th and 95th percentile weight, children of 5th, 50th and 95th percentile weight, and the developing fetus of 15, 25, and 38 weeks after conception. Additional sensitivity studies were performed to evaluate effects of passenger positioning within the scanner, energy spectrum and beam geometry, as well as failure mode analyses. Results for routine operations yielded a maximum effective dose to the adult and pediatric passengers of 15 and 25 nSv per screen, respectively. The developing fetus received a maximum organ dose and whole body dose of 16 nGy and 8.5 nGy per screen, respectively. The sensitivity analyses indicated that variations in positioning, energy spectra, and beam geometry yielded a range of effective doses per screen that were an order of magnitude below the ANSI recommendation.

An image-based skeletal dosimetry model for the ICRP reference adult female-internal electron sources.

An image-based skeletal dosimetry model for internal electron sources was created for the ICRP-defined reference adult female. Many previous skeletal dosimetry models, which are still employed in commonly used internal dosimetry software, do not properly account for electron escape from trabecular spongiosa, electron cross-fire from cortical bone, and the impact of marrow cellularity on active marrow self-irradiation. Furthermore, these existing models do not employ the current ICRP definition of a 50 µm bone endosteum (or shallow marrow). Each of these limitations was addressed in the present study. Electron transport was completed to determine specific absorbed fractions to both active and shallow marrow of the skeletal regions of the University of Florida reference adult female. The skeletal macrostructure and microstructure were modeled separately. The bone macrostructure was based on the whole-body hybrid computational phantom of the UF series of reference models, while the bone microstructure was derived from microCT images of skeletal region samples taken from a 45 years-old female cadaver. The active and shallow marrow are typically adopted as surrogate tissue regions for the hematopoietic stem cells and osteoprogenitor cells, respectively. Source tissues included active marrow, inactive marrow, trabecular bone volume, trabecular bone surfaces, cortical bone volume, and cortical bone surfaces. Marrow cellularity was varied from 10 to 100 percent for active marrow self-irradiation. All other sources were run at the defined ICRP Publication 70 cellularity for each bone site. A total of 33 discrete electron energies, ranging from 1 keV to 10 MeV, were either simulated or analytically modeled. The method of combining skeletal macrostructure and microstructure absorbed fractions assessed using MCNPX electron transport was found to yield results similar to those determined with the PIRT model applied to the UF adult male skeletal dosimetry model. Calculated skeletal averaged absorbed fractions for each source-target combination were found to follow similar trends of more recent dosimetry models (image-based models) but did not follow results from skeletal models based upon assumptions of an infinite expanse of trabecular spongiosa.

The UF Family of hybrid phantoms of the pregnant female for computational radiation dosimetry.

Efforts to assess in utero radiation doses and related quantities to the developing fetus should account for the presence of the surrounding maternal tissues. Maternal tissues can provide varying levels of protection to the fetus by shielding externally-emitted radiation or, alternatively, can become sources of internally-emitted radiation following the biokinetic uptake of medically-administered radiopharmaceuticals or radionuclides located in the surrounding environment--as in the case of the European Union's SOLO project (Epidemiological Studies of Exposed Southern Urals Populations). The University of Florida had previously addressed limitations in available computational phantom representation of the developing fetus by constructing a series of hybrid computational fetal phantoms at eight different ages and three weight percentiles. Using CT image sets of pregnant patients contoured using 3D-DOCTOR(TM), the eight 50th percentile fetal phantoms from that study were systematically combined in Rhinoceros(TM) with the UF adult non-pregnant female to yield a series of reference pregnant female phantoms at fetal ages 8, 10, 15, 20, 25, 30, 35 and 38 weeks post-conception. Deformable, non-uniform rational B-spline surfaces were utilized to alter contoured maternal anatomy in order to (1) accurately position and orient each fetus and surrounding maternal tissues and (2) match target masses of maternal soft tissue organs to reference data reported in the literature.

The UF family of hybrid phantoms of the developing human fetus for computational radiation dosimetry.

Historically, the development of computational phantoms for radiation dosimetry has primarily been directed at capturing and representing adult and pediatric anatomy, with less emphasis devoted to models of the human fetus. As concern grows over possible radiation-induced cancers from medical and non-medical exposures of the pregnant female, the need to better quantify fetal radiation doses, particularly at the organ-level, also increases. Studies such as the European Union's SOLO (Epidemiological Studies of Exposed Southern Urals Populations) hope to improve our understanding of cancer risks following chronic in utero radiation exposure. For projects such as SOLO, currently available fetal anatomic models do not provide sufficient anatomical detail for organ-level dose assessment. To address this need, two fetal hybrid computational phantoms were constructed using high-quality magnetic resonance imaging and computed tomography image sets obtained for two well-preserved fetal specimens aged 11.5 and 21 weeks post-conception. Individual soft tissue organs, bone sites and outer body contours were segmented from these images using 3D-DOCTOR™ and then imported to the 3D modeling software package Rhinoceros™ for further modeling and conversion of soft tissue organs, certain bone sites and outer body contours to deformable non-uniform rational B-spline surfaces. The two specimen-specific phantoms, along with a modified version of the 38 week UF hybrid newborn phantom, comprised a set of base phantoms from which a series of hybrid computational phantoms was derived for fetal ages 8, 10, 15, 20, 25, 30, 35 and 38 weeks post-conception. The methodology used to construct the series of phantoms accounted for the following age-dependent parameters: (1) variations in skeletal size and proportion, (2) bone-dependent variations in relative levels of bone growth, (3) variations in individual organ masses and total fetal masses and (4) statistical percentile variations in skeletal size, individual organ masses and total fetal masses. The resulting series of fetal hybrid computational phantoms is applicable to organ-level and bone-level internal and external radiation dosimetry for human fetuses of various ages and weight percentiles.