The diversity of autoimmune responses poses a formidable challenge to the development of antigen-specific tolerizing therapy. We developed 'myelin proteome' microarrays to profile the evolution of autoantibody responses in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Increased diversity of autoantibody responses in acute EAE predicted a more severe clinical course. Chronic EAE was associated with previously undescribed extensive intra- and intermolecular epitope spreading of autoreactive B-cell responses. Array analysis of autoantigens targeted in acute EAE was used to guide the choice of autoantigen cDNAs to be incorporated into expression plasmids so as to generate tolerizing vaccines. Tolerizing DNA vaccines encoding a greater number of array-determined myelin targets proved superior in treating established EAE and reduced epitope spreading of autoreactive B-cell responses. Proteomic monitoring of autoantibody responses provides a useful approach to monitor autoimmune disease and to develop and tailor disease- and patient-specific tolerizing DNA vaccines.

The purpose of this work was to extend the verification of Monte Carlo based methods for estimating radiation dose in computed tomography (CT) exams beyond a single CT scanner to a multidetector CT (MDCT) scanner, and from cylindrical CTDI phantom measurements to both cylindrical and physical anthropomorphic phantoms. Both cylindrical and physical anthropomorphic phantoms were scanned on an MDCT under the specified conditions. A pencil ionization chamber was used to record exposure for the cylindrical phantom, while MOSFET (metal oxide semiconductor field effect transistor) detectors were used to record exposure at the surface of the anthropomorphic phantom. Reference measurements were made in air at isocentre using the pencil ionization chamber under the specified conditions. Detailed Monte Carlo models were developed for the MDCT scanner to describe the x-ray source (spectra, bowtie filter, etc) and geometry factors (distance from focal spot to isocentre, source movement due to axial or helical scanning, etc). Models for the cylindrical (CTDI) phantoms were available from the previous work. For the anthropomorphic phantom, CT image data were used to create a detailed voxelized model of the phantom's geometry. Anthropomorphic phantom material compositions were provided by the manufacturer. A simulation of the physical scan was performed using the mathematical models of the scanner, phantom and specified scan parameters. Tallies were recorded at specific voxel locations corresponding to the MOSFET physical measurements. Simulations of air scans were performed to obtain normalization factors to convert results to absolute dose values. For the CTDI body (32 cm) phantom, measurements and simulation results agreed to within 3.5% across all conditions. For the anthropomorphic phantom, measured surface dose values from a contiguous axial scan showed significant variation and ranged from 8 mGy/100 mAs to 16 mGy/100 mAs. Results from helical scans of overlapping pitch (0.9375) and extended pitch (1.375) were also obtained. Comparisons between the MOSFET measurements and the absolute dose value derived from the Monte Carlo simulations demonstrate agreement in terms of absolute dose values as well as the spatially varying characteristics. This work demonstrates the ability to extend models from a single detector scanner using cylindrical phantoms to an MDCT scanner using both cylindrical and anthropomorphic phantoms. Future work will be extended to voxelized patient models of different sizes and to other MDCT scanners.

Purpose:A recent work has demonstrated the feasibility of estimating the dose to individual organs from multidetector CT exams using patient-specific, scanner-independent CTDI vol -to-organ-dose conversion coefficients. However, the previous study only investigated organ dose to a single patient model from a full-body helical CT scan. The purpose of this work was to extend the validity of this dose estimation technique to patients of any size undergoing a common clinical exam. This was done by determining the influence of patient size on organ dose conversion coefficients generated for typical abdominal CT exams. Methods: Monte Carlo simulations of abdominal exams were performed using models of 64-slice MDCT scanners from each of the four major manufacturers to obtain dose to radiosensitive organs for eight patient models of varying size, age, and gender. The scanner-specific organ doses were normalized by corresponding CTDI vol values and averaged across scanners to obtain scannerindependent CTDI vol -to-organ-dose conversion coefficients for each patient model. In order to obtain a metric for patient size, the outer perimeter of each patient was measured at the central slice of the abdominal scan region. Then, the relationship between CTDI vol -to-organ-dose conversion coefficients and patient perimeter was investigated for organs that were directly irradiated by the abdominal scan. These included organs that were either completely ͑"fully irradiated"͒ or partly ͑"partially irradiated"͒ contained within the abdominal exam region. Finally, dose to organs that were not at all contained within the scan region ͑"nonirradiated"͒ were compared to the doses delivered to fully irradiated organs. Results: CTDI vol -to-organ-dose conversion coefficients for fully irradiated abdominal organs had a strong exponential correlation with patient perimeter. Conversely, partially irradiated organs did not have a strong dependence on patient perimeter. In almost all cases, the doses delivered to nonirradiated organs were less than 5%, on average across patient models, of the mean dose of the fully irradiated organs. Conclusions: This work demonstrates the feasibility of calculating patient-specific, scannerindependent CTDI vol -to-organ-dose conversion coefficients for fully irradiated organs in patients undergoing typical abdominal CT exams. A method to calculate patient-specific, scanner-specific, and exam-specific organ dose estimates that requires only knowledge of the CTDI vol for the scan protocol and the patient's perimeter is thus possible. This method will have to be extended in future 820 820 Med. Phys. 38 "2…,

This work has revealed that there is considerable variation among modern MDCT scanners in both CTDIvol and organ dose values. Because these variations are similar, CTDIvol can be used as a normalization factor with excellent results. This demonstrates the feasibility of establishing scanner-independent organ dose estimates by using CTDIvol to account for the differences between scanners.

Purpose:To use Monte Carlo simulations of a current-technology multidetector computed tomographic (CT) scanner to investigate fetal radiation dose resulting from an abdominal and pelvic examination for a range of actual patient anatomies that include variation in gestational age and maternal size. Materials and Methods:Institutional review board approval was obtained for this HIPAA-compliant retrospective study. Twenty-four models of maternal and fetal anatomy were created from image data from pregnant patients who had previously undergone clinically indicated CT examination. Gestational age ranged from less than 5 weeks to 36 weeks. Simulated helical scans of the abdominal and pelvic region were performed, and a normalized dose (in milligrays per 100 mAs) was calculated for each fetus. Stepwise multiple linear regression was performed to analyze the correlation of dose with gestational age and anatomic measurements of maternal size and fetal location. Results were compared with several existing fetal dose estimation methods. Results:Normalized fetal dose estimates from the Monte Carlo simulations ranged from 7.3 to 14.3 mGy/100 mAs, with an average of 10.8 mGy/100 mAs. Previous methods yielded values of 10 -14 mGy/100 mAs. The correlation between gestational age and fetal dose was not significant (P ϭ .543). Normalized fetal dose decreased linearly with increasing patient perimeter (R 2 ϭ 0.681, P Ͻ .001), and a two-factor model with patient perimeter and fetal depth demonstrated a strong correlation with fetal dose (R 2 ϭ 0.799, P Ͻ .002). Conclusion:A method for the estimation of fetal dose from models of actual patient anatomy that represented a range of gestational age and patient size was developed. Fetal dose correlated with maternal perimeter and varied more than previously recognized. This correlation improves when maternal size and fetal depth are combined. Note: This copy is for your personal, non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, use the Radiology Reprints form at the end of this article. D iagnostic computed tomographic(CT) imaging is sometimes necessary in a pregnant patient. When a radiologist needs to decide if the diagnostic benefits will outweigh the risks of radiation, it is important to have a reasonably accurate estimate of the radiation dose that the conceptus (fetus or embryo) will receive. Furthermore, in cases in which pregnancy is discovered during or after CT examination, the patient and/or physician may request an estimate of the radiation dose received by the conceptus. For the remainder of this article, the term fetus will be used to refer to either an embryo or a fetus and will therefore be used to describe a conceptus at any gestational age.It is not known definitively how much radiation dose a fetus receives during CT examination, because this cannot be measured directly. Some methods to estimate fetal dose exist, but these estimates are limited by their simplifying assumptions. Existing fetal dose estimation m...

The purpose of this study was to present a method for generating x-ray source models for performing Monte Carlo ͑MC͒ radiation dosimetry simulations of multidetector row CT ͑MDCT͒ scanners. These so-called "equivalent" source models consist of an energy spectrum and filtration description that are generated based wholly on the measured values and can be used in place of proprietary manufacturer's data for scanner-specific MDCT MC simulations. Required measurements include the half value layers ͑HVL 1 and HVL 2 ͒ and the bowtie profile ͑exposure values across the fan beam͒ for the MDCT scanner of interest. Using these measured values, a method was described ͑a͒ to numerically construct a spectrum with the calculated HVLs approximately equal to those measured ͑equivalent spectrum͒ and then ͑b͒ to determine a filtration scheme ͑equivalent filter͒ that attenuates the equivalent spectrum in a similar fashion as the actual filtration attenuates the actual x-ray beam, as measured by the bowtie profile measurements. Using this method, two types of equivalent source models were generated: One using a spectrum based on both HVL 1 and HVL 2 measurements and its corresponding filtration scheme and the second consisting of a spectrum based only on the measured HVL 1 and its corresponding filtration scheme. Finally, a third type of source model was built based on the spectrum and filtration data provided by the scanner's manufacturer. MC simulations using each of these three source model types were evaluated by comparing the accuracy of multiple CT dose index ͑CTDI͒ simulations to measured CTDI values for 64-slice scanners from the four major MDCT manufacturers. Comprehensive evaluations were carried out for each scanner using each kVp and bowtie filter combination available. CTDI experiments were performed for both head ͑16 cm in diameter͒ and body ͑32 cm in diameter͒ CTDI phantoms using both central and peripheral measurement positions. Both equivalent source model types result in simulations with an average root mean square ͑RMS͒ error between the measured and simulated values of approximately 5% across all scanner and bowtie filter combinations, all kVps, both phantom sizes, and both measurement positions, while data provided from the manufacturers gave an average RMS error of approximately 12% pooled across all conditions. While there was no statistically significant difference between the two types of equivalent source models, both of these model types were shown to be statistically significantly different from the source model based on manufacturer's data. These results demonstrate that an equivalent source model based only on measured values can be used in place of manufacturer's data for Monte Carlo simulations for MDCT dosimetry.

The purpose of this work is to examine the effects of patient size on radiation dose from CT scans. To perform these investigations, we used Monte Carlo simulation methods with detailed models of both patients and multidetector computed tomography (MDCT) scanners. A family of three-dimensional, voxelized patient models previously developed and validated by the GSF was implemented as input files using the Monte Carlo code MCNPX. These patient models represent a range of patient sizes and ages (8 weeks to 48 years) and have all radiosensitive organs previously identified and segmented, allowing the estimation of dose to any individual organ and calculation of patient effective dose. To estimate radiation dose, every voxel in each patient model was assigned both a specific organ index number and an elemental composition and mass density. Simulated CT scans of each voxelized patient model were performed using a previously developed MDCT source model that includes scanner specific spectra, including bowtie filter, scanner geometry and helical source path. The scan simulations in this work include a whole-body scan protocol and a thoracic CT scan protocol, each performed with fixed tube current. The whole-body scan simulation yielded a predictable decrease in effective dose as a function of increasing patient weight. Results from analysis of individual organs demonstrated similar trends, but with some individual variations. A comparison with a conventional dose estimation method using the ImPACT spreadsheet yielded an effective dose of 0.14 mSv mAs(-1) for the whole-body scan. This result is lower than the simulations on the voxelized model designated 'Irene' (0.15 mSv mAs(-1)) and higher than the models 'Donna' and 'Golem' (0.12 mSv mAs(-1)). For the thoracic scan protocol, the ImPACT spreadsheet estimates an effective dose of 0.037 mSv mAs(-1), which falls between the calculated values for Irene (0.042 mSv mAs(-1)) and Donna (0.031 mSv mAs(-1)) and is higher relative to Golem (0.025 mSv mAs(-1)). This work demonstrates the ability to estimate both individual organ and effective doses from any arbitrary CT scan protocol on individual patient-based models and to provide estimates of the effect of patient size on these dose metrics.

Tube current modulation was designed to reduce radiation dose in CT imaging while maintaining overall image quality. This study aims to develop a method for evaluating the effects of tube current modulation (TCM) on organ dose in CT exams of actual patient anatomy. This method was validated by simulating a TCM and a fixed tube current chest CT exam on 30 voxelized patient models and estimating the radiation dose to each patient’s glandular breast tissue. This new method for estimating organ dose was compared with other conventional estimates of dose reduction. Thirty detailed voxelized models of patient anatomy were created based on image data from female patients who had previously undergone clinically indicated CT scans including the chest area. As an indicator of patient size, the perimeter of the patient was measured on the image containing at least one nipple using a semi-automated technique. The breasts were contoured on each image set by a radiologist and glandular tissue was semi-automatically segmented from this region. Previously validated Monte Carlo models of two multidetector CT scanners were used, taking into account details about the source spectra, filtration, collimation and geometry of the scanner. TCM data were obtained from each patient’s clinical scan and factored into the model to simulate the effects of TCM. For each patient model, two exams were simulated: a fixed tube current chest CT and a tube current modulated chest CT. X-ray photons were transported through the anatomy of the voxelized patient models, and radiation dose was tallied in the glandular breast tissue. The resulting doses from the tube current modulated simulations were compared to the results obtained from simulations performed using a fixed mA value. The average radiation dose to the glandular breast tissue from a fixed tube current scan across all patient models was 19 mGy. The average reduction in breast dose using the tube current modulated scan was 17%. Results were size dependent with smaller patients getting better dose reduction (up to 64% reduction) and larger patients getting a smaller reduction, and in some cases the dose actually increased when using tube current modulation (up to 41% increase). The results indicate that radiation dose to glandular breast tissue generally decreases with the use of tube current modulated CT acquisition, but that patient size (and in some cases patient positioning) may affect dose reduction.