On the biological basis for competing macroscopic dose descriptors for kilovoltage dosimetry: cellular dosimetry for brachytherapy and diagnostic radiology.

The purpose of this work is to investigate how alternative macroscopic dose descriptors track absorbed dose to biologically relevant subcellular targets via Monte Carlo (MC) analysis of cellular models for a variety of cancerous and normal soft tissues for kilovoltage radiation. The relative mass distributions of water, light inorganic elements, and protein components of nuclear and cytoplasm compartments for various tissues are determined from a literature review. These data are used to develop representative cell models to demonstrate the range of mass elemental compositions of these subcellular structures encountered in the literature from which radiological quantities (energy absorption and attenuation coefficients; stopping powers) are computed. Using representative models of cell clusters, doses to subcellular targets are computed using MC simulation for photon sources of energies between 20 and 370 keV and are compared to bulk medium dose descriptors. It is found that cells contain significant and varying mass fractions of protein and inorganic elements, leading to variations in mass energy absorption coefficients for cytoplasm and nuclear media as large as 10% compared to water for sub-50 keV photons. Doses to subcellular structures vary by as much as 23% compared to doses to the corresponding average bulk medium or to small water cavities embedded in the bulk medium. Relationships between cellular target doses and doses to the bulk medium or to a small water cavity embedded in the bulk medium are sensitive to source energy and cell morphology, particularly for lower energy sources, e.g., low energy brachytherapy (<50 keV). Results suggest that cells in cancerous and normal soft tissues are generally not radiologically equivalent to either water or the corresponding average bulk tissue. For kilovoltage photon sources, neither dose to bulk medium nor dose to water quantitatively tracks energy imparted to biologically relevant subcellular targets for the range of cellular morphologies and tissues considered.

WE-E-213CD-05: A Non-Rigid Image Registration Algorithm That Accommodates Organ Segmentation Error.

PURPOSE: To introduce a new deformable image registration algorithm based on surface matching that accommodates organ delineation error in daily Cone-beam CT images based on a priori knowledge of inter-observer segmentation uncertainty. METHODS: The dataset includes four prostate cancer patients who underwent primary external beam radiotherapy and had tumors that were confined to the prostate. All imaging was performed without intravenous contrast. Organ surface segmentation errors in a multiple observer-contouring study on the pelvic organs in Fan-beam CT (FBCT) and Cone-beam CT (CBCT) were estimated from the training dataset. A novel deformable image registration algorithm is presented where the organ surface matching is penalized by this error. Portions of the organ surface that are delineated reliably are used to guide the registration whereas the portions that are highly uncertain are ignored. This approach reduces the impact of delineation errors in CBCT. An evaluation experiment compares three algorithms, namely intensity-only registration (INT), equally-weighted surface and image registration (EWSIR) and the proposed uncertainty- weighted surface and image registration. RESULTS: The surface dissimilarity was reduced from 0.172 to 0.134, 0.043 and 0.044 respectively after registration. The Jacobian of the transformation found by the proposed method was closer to one than that of EWSIR in the prostate. CONCLUSIONS: In prostate external-beam radiotherapy, slice-by-slice 2D manual contouring has variable spatial accuracy. For deformable image registration methods that match segmented surfaces, regions of high inaccuracy can misguide the registration. In contrast to the image registration methods where the FBCT and CBCT surfaces (or other features) are assumed to be exact, our method takes this uncertainty into account. Preliminary results show an improved registration performance suggesting a potential use in IGRT. This work was supported by National Cancer Institute Grant No. P01 CA 116602.

A comparison of HDR brachytherapy and IMRT techniques for dose escalation in prostate cancer: a radiobiological modeling study.

A course of one to three large fractions of high dose rate (HDR) interstitial brachytherapy is an attractive alternative to intensity modulated radiation therapy (IMRT) for delivering boost doses to the prostate in combination with additional external beam irradiation for intermediate risk disease. The purpose of this work is to quantitatively compare single-fraction HDR boosts to biologically equivalent fractionated IMRT boosts, assuming idealized image guided delivery (igIMRT) and conventional delivery (cIMRT). For nine prostate patients, both seven-field IMRT and HDR boosts were planned. The linear-quadratic model was used to compute biologically equivalent dose prescriptions. The cIMRT plan was evaluated as a static plan and with simulated random and setup errors. The authors conclude that HDR delivery produces a therapeutic ratio which is significantly better than the conventional IMRT and comparable to or better than the igIMRT delivery. For the HDR, the rectal gBEUD analysis is strongly influenced by high dose DVH tails. A saturation BED, beyond which no further injury can occur, must be assumed. Modeling of organ motion uncertainties yields mean outcomes similar to static plan outcomes.

Anniversary paper: fifty years of AAPM involvement in radiation dosimetry.

This article reviews the involvement of the AAPM in various aspects of radiation dosimetry over its 50 year history, emphasizing the especially important role that external beam dosimetry played in the early formation of the organization. Topics covered include the AAPM's involvement with external beam and x-ray dosimetry protocols, brachytherapy dosimetry, primary standards laboratories, accredited dosimetry chains, and audits for machine calibrations through the Radiological Physics Center.

Respiratory regularity gated 4D CT acquisition: concepts and proof of principle.

Four-dimensional CT images are generally sorted through a post-acquisition procedure correlating images with a time-synchronized external respiration signal. The patient's ability to maintain reproducible respiration is the limiting factor during 4D CT, where artifacts occur in approximately 85% of scans with current technology. To reduce these artifacts and their subsequent effects during radiotherapy planning, a method for improved 4D CT image acquisition that relies on gating 4D CT acquisition based on the real time monitoring of the respiration signal has been proposed. The respiration signal and CT data acquisition are linked, such that data from irregular breathing cycles, which cause artifacts, are not acquired by gating CT acquisition by the respiratory signal. A proof-of-principle application of the respiratory regularity gated 4D CT method using patient respiratory signals demonstrates the potential of this method to reduce artifacts currently found in 4D CT scans. Numerical simulations indicate a potential reduction in motion within a respiratory phase bin by 20-40% depending on tolerances chosen. Additional advantages of the proposed method are dose reduction by eliminating unnecessary oversampling and obviating the need for post-processing to create the 4D CT data set.

Haplotyping of the canine MHC without the need for DLA typing.

The genomic matching technique has proven useful in MHC haplotyping in humans. We have adopted a similar approach in Australian cattle dogs and report that genotyping can be achieved with a single assay.

Indels and imperfect duplication have driven the evolution of human Complement Receptor 1 (CR1) and CR1-like from their precursor CR1 alpha: importance of functional sets.

This study examines the effects of duplication and insertions-deletions (indels) by comparing human complement receptor 1 (CR1) and human CR1-like (CR1L) with syntenic genes from four other vertebrates (chimpanzee, baboon, rat, and mouse). By phylogenetic analysis, the domains of these genes can be classified into 10 distinct subfamilies (a, b, c, d, e, f, g(-like), h, j, and k), which have been largely conserved throughout vertebrate and invertebrate evolution. In spite of many complex and diverse duplications and indels, the subfamily order of domains (a, j, e, f, b, k, d, g(-like)) has been maintained. The number of domain sets has increased progressively, thereby expanding the functional repertoire.

Dependence of radiochromic film response kinetics on fractionated doses.

Because the rate and magnitude of the post-exposure growth of the MD-55 radiochromic film (RCF) dosimeter response depends significantly on total dose, we have investigated the influence of fractionation and protracted dose delivery on optical density (OD) as a function of total dose and the exposure-to-densitometry time interval for a 633-nm scanning laser densitometer. Both measurements and models demonstrate that fractionation induces transient OD over responses, which can be as large as 20%, but rapidly dissipate within 24 h. However, the superposition model predicts 2-5% over responses that persist as long as 700 h.

Genomic analysis reveals a duplication of eight rather than seven short consensus repeats in primate CR1 and CR1L: evidence for an additional set shared between CR1 and CR2.

We report the discovery of previously unrecognised short consensus repeats (SCRs) within human and chimpanzee CR1 and CR1L. Analysis of available genomic, protein and expression databases suggests that these are actually genomic remnants of SCRs previously reported in other complement control proteins (CCPs). Comparison with the nucleotide motifs of the 11 defined subfamilies of SCRs justifies the designation g-like because of the close similarity to the g subfamily found in CR2 and MCP. To date, we have identified five such SCRs in human and chimpanzee CR1, one in human and chimpanzee CR1L, but none in either rat or mouse Crry in keeping with the number of internal duplications of the long homologous repeat (LHR) found in CR1 and CR1L. In fact, at the genomic level, the ancestral LHR must have contained eight SCRs rather than seven as previously thought. Since g-like SCRs are found immediately downstream of d SCRs, we suggest that there must have been a functional dg set which has been retained by CR2 and MCP but which is degenerate in CR1 or CR1L. Interestingly, dg is also present in the CR2 component of mouse CR1. The degeneration of the g SCR must have occurred prior to the formation of primate CR1L and prior to the duplication events which resulted in primate CR1. In this context, the apparent conservation of g-like SCRs may be surprising and may suggest the existence of mechanisms unrelated to protein coding. These results provide examples of the many processes which have contributed to the evolution of the extensive repertoire of CCPs.

Dependence of radiochromic film optical density post-exposure kinetics on dose and dose fractionation.

Radiochromic film (RCF) has been shown to be a precise and accurate secondary planar dosimeter for acute exposure radiation fields. However, its application to low dose-rate brachytherapy has been questioned because of possible dose-rate effects. To address this concern, we have measured the optical density (OD) of Model 55-2 RCF as a function of time (interval between the completion of irradiation and densitometry using a 633 nm laser scanner) following exposure (from less than 1 hour to 90 days) for single and split doses from 1 Gy to 100 Gy. Our work demonstrates that film darkening as a function of post-irradiation time depends significantly on total dose, with films exposed to lower doses developing faster than films given higher doses. At 1 Gy, the OD 90 days after exposure is 200% larger than that measured 1 h after exposure compared to a 20% increase over 90 days for doses larger than 20 Gy. An empirical model with time-independent, fast and slow growth terms was used to fit single exposure data. The dependence of the resulting best-fit parameters on dose was investigated. Splitting the dose into two fractions (20 Gy followed by doses of 1-80 Gy 24 h later) results in modest post-irradiation time-dependent changes in the total optical density (at most 15% at small doses), which dissipates within 20 hours following the second exposure. This experimental finding is consistent with the predictions of a simple cumulative dose superposition model. Overall, both experimental and empirical modeling suggest that dose-rate effects may be relatively small despite the strong dependence of film darkening kinetics on total dose. However, more experimental evaluation of radiochromic film response dependence on dose rate and dose-time-fractionation patterns is needed.

Measured transverse-axis dosimetric parameters of the model STM1251 125I interstitial source.

The recent popularity of permanent implants for treatment of prostate cancer has created a large demand for low energy seed sources. Vendors have introduced new source designs to meet this demand. The AAPM has recommended that all low energy interstitial brachytherapy seed sources be subjected to independent dosimetric evaluations, preferably using experimental measurements as well as Monte Carlo calculations. This work presents the results of Thermo-Luminescence Dosimeter (TLD) measurements of dosimetric parameters on the transverse axis of a new 125I seed source, the Source Tech Medical STM1251 125I seed. Experimental measurements were performed in a Solid Water phantom, with the results corrected to values for liquid water using Monte Carlo calculated correction factors. The parameters measured include the dose rate constant and values of the radial dose function at distances of 0.5 cm through 5 cm. The measured dose rate constant in liquid water for the STM1251 125I seed was 1.039 cGy/U-hr. Measured radial dose function values agreed with Monte Carlo calculated ones to within 10%. These measurements therefore confirm the modeling and simulation of Monte Carlo calculations for this 125I source design, within the statistical uncertainties of the calculation and measurement techniques.

Accurate localization of intracavitary brachytherapy applicators from 3D CT imaging studies.

PURPOSE: To present an accurate method to identify the positions and orientations of intracavitary (ICT) brachytherapy applicators imaged in 3D CT scans, in support of Monte Carlo photon-transport simulations, enabling accurate dose modeling in the presence of applicator shielding and interapplicator attenuation. MATERIALS AND METHODS: The method consists of finding the transformation that maximizes the coincidence between the known 3D shapes of each applicator component (colpostats and tandem) with the volume defined by contours of the corresponding surface on each CT slice. We use this technique to localize Fletcher-Suit CT-compatible applicators for three cervix cancer patients using post-implant CT examinations (3 mm slice thickness and separation). Dose distributions in 1-to-1 registration with the underlying CT anatomy are derived from 3D Monte Carlo photon-transport simulations incorporating each applicator's internal geometry (source encapsulation, high-density shields, and applicator body) oriented in relation to the dose matrix according to the measured localization transformations. The precision and accuracy of our localization method are assessed using CT scans, in which the positions and orientations of dense rods and spheres (in a precision-machined phantom) were measured at various orientations relative to the gantry. RESULTS: Using this method, we register 3D Monte Carlo dose calculations directly onto post insertion patient CT studies. Using CT studies of a precisely machined phantom, the absolute accuracy of the method was found to be +/-0.2 mm in plane, and +/-0.3 mm in the axial direction while its precision was +/-0.2 mm in plane, and +/-0.2 mm axially. CONCLUSION: We have developed a novel, and accurate technique to localize intracavitary brachytherapy applicators in 3D CT imaging studies, which supports 3D dose planning involving detailed 3D Monte Carlo dose calculations, modeling source positions, shielding and interapplicator shielding, accurately.

High dose ratio (HDR) cervical ring applicator to control bleeding from cervical carcinoma.

The objective of this study was to evaluate the use of the high dose rate (HDR) cervical ring applicator to control acute cervical bleeding from carcinoma of the uterine cervix. This study consists of 15 patients presenting with invasive carcinoma of the uterine cervix with acute vaginal bleeding requiring transfusion. Initial irradiation, delivered emergently because of vaginal bleeding, consisted of two fractions (5 Gy each fraction to the surface of the cervix) utilizing the HDR intracavitary vaginal ring applicator. Two fractions were administered at one week intervals for a total of 10 Gy to the surface of the cervix. Irradiation doses from the HDR ring applications were not considered into the composite total dose to point A. Diagnostic imaging evaluation and initiation of external irradiation were commenced during this initial weekly interval between fractions. Vaginal bleeding requiring no additional transfusions was achieved in 93% (14/15) of patients. No acute or long-term Grades 3, 4, or 5 bowel or bladder sequelae were noted. In conclusion, HDR cervical ring brachytherapy is effective in controlling acute vaginal bleeding and can be delivered without undue acute or long-term toxicity.

Multigroup discrete ordinates modeling of 125I 6702 seed dose distributions using a broad energy-group cross section representation.

Our purpose in this work is to demonstrate that the efficiency of dose-rate computations in 125I brachytherapy, using multigroup discrete ordinates radiation transport simulations, can be significantly enhanced using broad energy group cross sections without a loss of accuracy. To this end, the DANTSYS multigroup discrete ordinates neutral particle transport code was used to estimate the absorbed dose-rate distributions around an 125I-model 6702 seed in two-dimensional (2-D) cylindrical R-Z geometry for four different problems spanning the geometries found in clinical practice. First, simulations with a high resolution 210 energy groups library were used to analyze the photon flux spectral distribution throughout this set of problems. These distributions were used to design an energy group structure consisting of three broad groups along with suitable weighting functions from which the three-group cross sections were derived. The accuracy of 2-D DANTSYS dose-rate calculations was benchmarked against parallel Monte Carlo simulations. Ray effects were remedied by using the DANTSYS internal first collision source algorithm. It is demonstrated that the 125I primary photon spectrum leads to inappropriate weighting functions. An accuracy of +/-5% is achieved in the four problem geometries considered using geometry-independent three-group libraries derived from either material-specific weighting functions or a single material-independent weighting function. Agreement between Monte Carlo and the three-group DANTSYS calculations, within three standard Monte Carlo deviations, is observed everywhere except for a limited region along the Z axis of rotational symmetry, where ray effects are difficult to mitigate. The three-group DANTSYS calculations are 10-13 times faster than ones with a 210-group cross section library for 125I dosimetry problems. Compared to 2-D EGS4 Monte Carlo calculations, the 3-group DANTSYS simulations are a 100-fold more efficient. Provided that these efficiency gains can be sustained in three-dimensional geometries, the results suggest that discrete ordinates simulations may have the potential to serve as an efficient and accurate dose-calculation algorithm for low-energy brachytherapy treatment planning.

Monte Carlo-aided dosimetry of the new Bebig IsoSeed 103Pd interstitial brachytherapy seed.

A new model 103Pd interstitial brachytherapy source, the IsoSeed 103Pd, was recently introduced by Bebig Isotopentechnik und Umweltdiagnostik GmbH for permanent implant applications. This study presents the first quantitative theoretical study of the seed's dosimetric quantities. Monte Carlo photon transport (MCPT) simulation techniques have been used to evaluate the dose-rate distributions around the model IsoSeed 103Pd source in liquid water and air phantoms. These results have been used to calculate and tabulate the anisotropy function, F(r, theta), radial dose function, g(r), and anisotropy factors, phi(r), and dose-rate constant as defined by AAPM Task Group 43 (TG-43) Report. Cartesian "away" and "along" tables, giving the dose rates per unit air-kerma strength in water in the range 0.1-3 cm distance around the seed have also been tabulated. The dose-rate constant, lambda, was evaluated by simulating the wide-angle, free-air chamber (WAFAC) calibration geometry recently implemented by NIST (National Institute of Standards and Technology) to realize the primary standard of air-kerma strength (SK,N99) for low-energy photon-emitting brachytherapy sources. The dose-rate constant has been found to be lambda=0.660+/-0.017 in units of dose-rate per unit air-kerma strength (cGy x h(-1) x U(-1)).

Deblurring subject to nonnegativity constraints when known functions are present with application to object-constrained computerized tomography.

The reconstruction of tomographic images is often treated as a linear deblurring problem. When a high-density, man-made metal object is present somewhere in the image field, it is a deblurring problem in which the unknown function has a component that is known except for some location and orientation parameters. We first address general linear deblurring problems in which a known function having unknown parameters is present. We then show how the resulting iterative solution can be applied to tomographic imaging in the presence of man-made foreign objects, and we apply the result, in particular, to X-ray computed tomography imaging used in support of brachytherapy treatment of advanced cervical cancer.

Thermoluminescent dosimetry of the Symmetra 125I model I25.S06 interstitial brachytherapy seed.

As the efficacy of brachytherapy prostate treatment is becoming realized, new models of 125I seeds are being introduced. In this article we present thermoluminescent dosimetry (TLD) in a solid water phantom for a new design of 125I seed (UroMed/Bebig Symmetra, Model I25.S06). TLD cubes, LiF TLD-100, from Bicron (Solon, OH) with dimension 1 x 1 x 1 mm3 were irradiated at various distances from the seed at angles ranging from 0 degrees to 90 degrees in 10 degrees increments. The TLD detectors were calibrated by irradiation in a 60Co teletherapy beam. Monte Carlo simulation was used to account for TLD energy dependence and the deviation of solid water composition (as determined by chemical analysis of a sample) from liquid water. Dose rates per unit air kerma strength were determined based on calibrations traceable to the 1999 NIST standard (corrected for NIST measurement errors made in 1999) for the Symmetra seed. Dose data is presented in TG-43 format as a function of distance and angle. Values for lambda, F(r, theta), g(r), and the anisotropy constant are obtained for use in radiation treatment planning (RTP) software. The dose rate constant was determined to be 1.033+/-6.4% cGy h(-1) U(-1), which is comparable to model 6702 and higher than model 6711. We find the relative dose distributions of the Symmetra seed are similar to model 6702, and less anisotropic than model 6711. After accounting for deviation of measured solid water composition from the manufacturer's specification, good agreement between TLD results and Monte-Carlo-aided values was found.

Image-based dose planning of intracavitary brachytherapy: registration of serial-imaging studies using deformable anatomic templates.

PURPOSE: To demonstrate that high-dimensional voxel-to-voxel transformations, derived from continuum mechanics models of the underlying pelvic tissues, can be used to register computed tomography (CT) serial examinations into a single anatomic frame of reference for cumulative dose calculations. METHODS AND MATERIALS: Three patients with locally advanced cervix cancer were treated with CT-compatible intracavitary (ICT) applicators. Each patient underwent five volumetric CT examinations: before initiating treatment, and immediately before and after the first and second ICT insertions, respectively. Each serial examination was rigidly registered to the patient's first ICT examination by aligning the bony anatomy. Detailed nonrigid alignment for organs (or targets) of interest was subsequently achieved by deforming the CT exams as a viscous-fluid, described by the Navier-Stokes equation, until the coincidence with the corresponding targets on CT image was maximized. In cases where ICT insertion induced very large and topologically complex rearrangements of pelvic organs, e.g., extreme uterine canal reorientation following tandem insertion, a viscous-fluid-landmark transformation was used to produce an initial registration. RESULTS: For all three patients, reasonable registrations for organs (or targets) of interest were achieved. Fluid-landmark initialization was required in 4 of the 11 registrations. Relative to the best rigid bony landmark alignment, the viscous-fluid registration resulted in average soft-tissue displacements from 2.8 to 28.1 mm, and improved organ coincidence from the range of 5.2% to 72.2% to the range of 90.6% to 100%. Compared to the viscous-fluid transformation, global registration of bony anatomy mismatched 5% or more of the contoured organ volumes by 15-25 mm. CONCLUSION: Pelvic soft-tissue structures undergo large deformations and displacements during the external-beam and multiple-ICT course of radiation therapy for locally advanced cervix cancer. These changes cannot be modeled by the conventional rigid landmark transformation method. In the current study, we found that the deformable anatomic template registration method, based on continuum-mechanics models of deformation, successfully described these large anatomic shape changes before and after ICT. These promising modeling results indicate that realistic registration of the cumulative dose distribution to the organs (or targets) of interest for radiation therapy of cervical cancers is achievable.

Monte Carlo-aided dosimetry of the Source Tech Medical Model STM1251 I-125 interstitial brachytherapy source.

We have used Monte Carlo photon transport simulations to calculate the dosimetric parameters of a new 125I seed, the Source Tech Medical Model STM125I source for interstitial brachytherapy. We followed the recommendations of the AAPM Task Group 43 and determined the following parameters: dose-rate constant, radial dose function, anisotropy function, anisotropy factor, and anisotropy constant. The recently (January 1999) revised National Institute of Standards and Technology I-125 standard for air-kerma strength calibration was taken into account as well as updated interaction cross-section data. The calculated dose-rate constant, when normalized to the simulated wide-angle, free-air chamber measurement of air-kerma strength, is 0.980 cGy h(-1) U(-1). The calculated radial dose function for the Model STM 1251 source is more penetrating than that of the model 6711 seed (by 18% at 5 cm distance), but agrees closely (within statistical errors) with that of the model 6702 seed up to distances of 10 cm. The STM125I source anisotropy functions indicate that its dose distribution is somewhat more anisotropic than that of the model 6702 and 6711 seeds at 1 cm distance but is comparable at larger distances. The Model STM125I anisotropy constant is very similar to that of the model 6711, 6702, and MED363I A/M seeds.