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...