New three-dimensional reconstruction technique at minimal dose conditions in electron microscopy.
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OBJECTIVE: At the end of 2000, certain diseases including leukemia were reported among soldiers who participated in the Balkan and in the Gulf wars. Depleted uranium used during these conflicts was considered as a possible cause. Its radiotoxicity is close to that of natural uranium. This paper reviews the epidemiological knowledge of uranium, the means of exposure and the associated risk of cancer. METHODS: The only available epidemiological data concerns nuclear workers exposed to uranium. A review of the international literature is proposed by distinguishing between uranium miners and other workers of the nuclear industry. French studies are described in details. RESULTS: In ionizing radiation epidemiology, contamination by uranium is often cited as a risk factor, but the dose-effect relationship is rarely studied. Retrospective assessment of individual exposure is generally insufficient. Moreover, it is difficult to distinguish between uranium radiotoxicity, its chemical toxicity and the radiotoxicity of its progeny. A causal relation between lung cancer and radon exposure, a gas derived from the decay of uranium, has been demonstrated in epidemiological studies of miners. Among other nuclear workers exposed to uranium, there is a mortality deficit from all causes (healthy worker effect). No cancer site appears systematically in excess compared to the national population; very few studies describe a dose-response relationship. CONCLUSION: Only studies with a precise reconstruction of doses and sufficient numbers of workers will allow a better assessment of risks associated with uranium exposure at levels encountered in industry or during conflicts using depleted uranium weapons.
In high dose rate prostate brachytherapy, inadequate reconstruction of catheter geometry in treatment planning may result in erroneous dose delivery. Catheters may be digitized with: (1) Parallel reconstruction: digitized at only one point and assumed parallel and horizontal: (2) Straight reconstruction: digitized at both ends and assumed straight while at an angle: (3) Slice-by-slice reconstruction: digitized on all slices to obtain exact geometry. Our results show that individual catheters are often not parallel to each other, but fairly straight. Parallel reconstruction is the least accurate for dosimetric planning, while slice-by-slice reconstruction is time-consuming. Straight (two-point) reconstruction represents a balance between accuracy and efficiency.
PURPOSE: To study the short-term reproducibility of lung density measurements by multi-slice computed tomography (CT) using three different radiation doses and three reconstruction algorithms. MATERIAL AND METHODS: Twenty-five patients with smoker's emphysema and 25 patients with alpha1-antitrypsin deficiency underwent 3 scans at 2-week intervals. Low-dose protocol was applied, and images were reconstructed with bone, detail, and soft algorithms. Total lung volume (TLV), 15th percentile density (PD-15), and relative area at -910 Hounsfield units (RA-910) were obtained from the images using Pulmo-CMS software. Reproducibility of PD-15 and RA-910 and the influence of radiation dose, reconstruction algorithm, and type of emphysema were then analysed. RESULTS: The overall coefficient of variation of volume adjusted PD-15 for all combinations of radiation dose and reconstruction algorithm was 3.7%. The overall standard deviation of volume-adjusted RA-910 was 1.7% (corresponding to a coefficient of variation of 6.8%). Radiation dose, reconstruction algorithm, and type of emphysema had no significant influence on the reproducibility of PD-15 and RA-910. However, bone algorithm and very low radiation dose result in overestimation of the extent of emphysema. CONCLUSION: Lung density measurement by CT is a sensitive marker for quantitating both subtypes of emphysema. A CT-protocol with radiation dose down to 16 mAs and soft or detail reconstruction algorithm is recommended.
High atomic number inserts, such as hip prostheses and dental fillings, cause streak artifacts on computed tomography (CT) images when filtered back-projection (FBP) methods are used. These streak artifacts severely degrade our ability to differentiate the tumor volume. Also, incorrect Hounsfield numbers yield incorrect electron density information that may lead to erroneous dose calculations, and, as a result, compromise clinical outcomes. The aim of this research was to evaluate the dosimetric consequences of artifacts during radiotherapy planning of a prostate patient containing a hip prosthesis. The CT numbers corresponding to an iron prosthesis were inserted into the right femoral head of an existing CT image set. This artifact-free image was used as the standard image set. CT projections through the image set formed the sinogram, from which filtered back projection and iterative deblurring methods were used to create reconstructed image sets. These reconstructed image sets contained artifacts. Prostate treatment plans were then calculated using a Monte Carlo system for the standard and reconstructed CT image sets. Close to the prosthesis, the CT numbers between the reconstructed and standard image sets differed substantially. However, because the CT number differences covered only a small area, the dose distributions on the reconstructed and standard image sets were not significantly different. The dose-volume histograms for the prostate, rectum, and bladder were virtually identical. Our results indicate that even though CT image artifacts restrict our ability to differentiate tumors and critical structures, the dose distributions for a prostate plan containing a hip prosthesis, calculated on both artifact-free image sets and image sets containing artifacts, are not significantly different.
The Varian multi-leaf collimator has a 14.5 cm leaf extension limit from each carriage. This means the target volumes in the head and neck region are sometimes too wide for standard width-modulated fields to provide adequate dose coverage. A solution is to set up asymmetric co-axial overlapping fields. This protects the MLC carriage while in return the MLC provides modulated dose blending in the field overlap region. Planar dose maps for coincident fields from the Pinnacle radiotherapy treatment planning system are compared with planar dose maps reconstructed from radiographic film and electronic portal images. The film and portal images show small leaf-jaw matchlines at each field overlap border. Linear profiles taken across each image show that the observed leaf-jaw matchlines from the accelerator images are not accounted for by the treatment planning system. Dose difference between film reconstructed electronic portal images and planning system are about 2.5 cGy in a modulated field at d(max). While the magnitude of the dose differences are small improved round end leaf modelling combined with a finer dose calculation grid may minimize the discrepancy between calculated and delivered dose.
Thyroid cancer incidence in the Bryansk region, the most contaminated area of Russia after the Chernobyl accident, is analyzed for the residents aged 15-69 y at the time of the accident (about 1 million persons according to the 1989 census) for the period from 1986 to 1998. Sex and age standardized incidence rates are presented and compared to the whole Russian population rates (SIR analysis). Also, a geographical correlation analysis is performed for incidence rates and mean thyroid doses at the district level, which provides a basis for preliminary estimation of radiation associated risks for the period 1991-1998 (to allow for a potential five year latent period). Thyroid doses were estimated based on the State official document "Methodology for reconstruction of dose from iodine radioisotopes in residents of the Russian Federation exposed to radioactive contamination as a result of the Chernobyl accident in 1986" (2000). Altogether, 1,051 thyroid cancer cases were detected in the Bryansk oncological dispensary from 1986 to 1998 and 769 from 1991 to 1998. Histological confirmation was available for 87% and 95% of these cases, respectively. Standardized incidence ratios (SIR) were 1.27 (95% CI = 0.92, 1.73) for the period 1986-1990 and 1.45 (95% CI = 1.20, 1.73) for the period 1991-1998 for males and 1.94 (95% CI = 1.70, 2.20) and 1.96 (95% CI = 1.82, 2.1) for females. The excess relative risk per 1 Gy (using external control) estimate for the period 1991-1998 was -0.4 (95% CI = -3.5, 2.7), -1.3 (95% CI = -2.8, 0.1) for males and females, respectively, and -0.6 (95% CI = -2.1, 0.8) for both sexes. Using internal controls, the excess relative risk (ERR(1Gy)) per unit dose of 1 Gy was found to be 0.7 with 95% CI (-2.3, 5.2) for males, -0.9 with 95% CI (-2.4, 0.8) for females and 0.0 with 95% CI (-1.4, 1.7) for males and females together. These results are discussed in the light of the quality of information available on thyroid cancer cases and screening campaigns carried out after the Chernobyl accident.
We present the mechanistic-based exposure and risk models, appraised with reported empirical data, to assess how the human exposure to airborne particulate matters (PMs) and carcinogenic polycyclic aromatic hydrocarbons (PAHs) during heavy incense burning episodes in temples. The models integrate size-dependent PM levels inside a temple from a published exploratory study associated with a human expiratory tract (HRT) model taking into account the personal exposure levels and size distributions in the HRT. The probabilistic exposure profiles of total-PAH levels inside a temple and internal PAHs doses are characterized by a physiologically based pharmacokinetic (PBPK) model with the reconstructed dose-response relationships based on an empirical three-parameter Hill equation model, describing PAHs toxicity for DNA adducts formation and lung tumor incidence responses in human white blood cells and lung. Results show that the alveolar-interstitial (AI) region has a lower mass median diameter (0.29 microm) than that in extrathoracic (ET(1), 0.37 microm), brochial (BB, 0.36 microm) and bronchiolar (bb, 0.32 microm) regions. The 50% probability (risk=0.5) of exceeding the DNA adducts frequency (DA(f)) ratio of 1.28 (95% CI: 0.55-2.40) and 1.78 (95% CI: 0.84-2.95) for external exposure of B[a]P and B[a]P(eq), respectively. The 10% (risk=0.1) probability or more of human affected by lung tumor is approximately 7.62x10(-5)% (95% CI: 3.39x10(-5)-1.71x10(-4)%) and 3.87x10(-4)% (95% CI: 1.72x10(-4)-8.69x10(-4)%) for internal exposure of B[a]P and B[a]P(eq), respectively. Our results implicate that exposure to smoke emitted from heavy incense burning may promote lung cancer risk. Our study provides a quantitative basis for objective risk prediction of heavy incense burning exposure in temples and for evaluating the effectiveness of management.
Conventional IMRT dose verification using film and ion chamber measurements is useful but limited with respect to the actual dose distribution received by the patient. The Monte Carlo simulation has been introduced as an independent dose verification tool for IMRT using the patient CT data and MLC leaf sequence files, which validates the dose calculation accuracy but not the plan delivery accuracy. In this work, we propose a Monte Carlo based IMRT dose verification method that reconstructs the patient dose distribution using the patient CT, actual beam data based on the information from the record and verify system (R/V), and the MLC log files obtained during dose delivery that record the MLC leaf positions and MUs delivered. Comparing the Monte Carlo dose calculation with the original IMRT plan using these data simultaneously validates the accuracy of both the IMRT dose calculation and beam delivery. Such log file based Monte Carlo simulations are expected to be employed as a useful and efficient IMRT QA modality to validate the dose delivered to the patient. We have run Monte Carlo simulations for eight IMRT prostate plans using this method and the results for the target dose were consistent with the original CORVUS treatment plans to within 3.0% and 2.0% with and without heterogeneity corrections in the dose calculation. However, significant dose deviations in nearby critical structures have been observed. The results showed that up to 9.0% of the bladder dose and up to 38.0% of the rectum dose, to which leaf position errors were found to contribute <2%, were underestimated by the CORVUS treatment planning system. The concept of average leaf position error has been defined to analyze MLC leaf position errors for an IMRT plan. A linear correlation between the target dose error and the average position error has been found based on log file based Monte Carlo simulations, showing that an average position error of 0.2 mm can result in a target dose error of about 1.0%.
To evaluate further the relationship between high-dose radiotherapy and leukemia incidence, a nested case-control study was conducted in a cohort of 22,753 women who were 18-month survivors of invasive breast cancer diagnosed from 1935 to 1972. Women treated for breast cancer after 1973 were excluded to minimize the possible confounding influence of treatment with chemotherapeutic agents. The cases had histologically confirmed leukemia reported to the Connecticut Tumor Registry (CTR) between 1935 and 1984. A total of 48 cases of leukemia following breast cancer were included in the study. Two controls were individually matched to each leukemia case on the basis of age, calendar year when diagnosed with breast cancer, and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. Local radiation doses to each of the 16 bone marrow components for each patient were reconstructed; the dose averaged over the entire body was 530 rad (5.3 Gy). Based on this dosage and assuming a linear relationship between dose and affect, a relative risk (RR) in excess of 10 would have been expected. However, there was little evidence that radiotherapy increased the overall risk of leukemia (RR = 1.16; 90% confidence interval [CI], 0.6 to 2.1). The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not significantly increased (RR = 1.8; n = 10); nor was the risk for all other forms of leukemia (RR = 1.0; n = 38). There was no indication that risk varied over categories of radiation dose. These data exclude an association between leukemia and radiotherapy for breast cancer of 2.2-fold with 90% confidence, and provide further evidence that cell death predominates over cell transformation when high radiation doses are delivered to limited volumes of tissue.
In order to better predict and understand the effects of radiopharmaceuticals used for therapy, it is necessary to determine more accurately the radiation absorbed dose to cells in tissue. Using thin-section autoradiography, the spatial distribution of sources relative to the cells can be obtained from a single section with micrometre resolution. By collecting and analysing serial sections, the 3D microscopic distribution of radionuclide relative to the cellular histology, and therefore the dose rate distribution, can be established. In this paper, a method of 3D reconstruction of serial sections is proposed, and measurements are reported of (i) the accuracy and reproducibility of quantitative autoradiography and (ii) the spatial precision with which tissue features from one section can be related to adjacent sections. Uncertainties in the activity determination for the specimen result from activity losses during tissue processing (4-11%), and the variation of grain count per unit activity between batches of serial sections (6-25%). Correlation of the section activity to grain count densities showed deviations ranging from 6-34%. The spatial alignment uncertainties were assessed using nylon fibre fiduciary markers incorporated into the tissue block, and compared to those for alignment based on internal tissue landmarks. The standard deviation for the variation in nylon fibre fiduciary alignment was measured to be 41 microns cm-1, compared to 69 microns cm-1 when internal tissue histology landmarks were used. In addition, tissue shrinkage during histological processing of up to 10% was observed. The implications of these measured activity and spatial distribution uncertainties upon the estimate of cellular dose rate distribution depends upon the range of the radiation emissions. For long-range beta particles, uncertainties in both the activity and spatial distribution translate linearly to the uncertainty in dose rate of < 15%. For short-range emitters (< 100 microns), such as alpha particle sources, the magnitude of the uncertainty in serial section alignment is comparable with the particle track length. Under these circumstances, dosimetric errors are introduced in proportion to the serial section alignment inaccuracy.
PURPOSE: To evaluate dose variations at bone/titanium interfaces in an experimental model designed to simulate postoperative radiotherapy in patients with mandibular reconstructions using a titanium hollow-screw osseointegrating reconstruction plate (THORP) system. MATERIALS AND METHODS: The model consisted of a 25 x 25 x 10 mm3 block of fresh bovine femoral diaphysis, to the surface of which a segment of THORP system reconstruction plate was fixed by means of a solid titanium screw 4 mm in diameter and 10 mm in length. Using specially designed thermoluminescent dosimeters (TLD) 2 mm in diameter and 0.13 mm in thickness, dose measurements were carried out at four distances from the screw axis (0.1, 0.3, 0.6, and 1 mm). 60Co and 6-MV photon beams were used at incidences both perpendicular and parallel ("axial") to the screw axis. RESULTS: For 6-MV X-ray beams incident perpendicular to the screw axis, the maximum dose enhancement (due to backscatter) and the maximum dose reduction (due to attenuation) at the bone/titanium interface were 5% (+/- 2%) and 6% (+/- 2%), respectively. The corresponding values for 60Co beams were 6% (+/- 5%) and 10% (+/- 5%). For the axial incidences, a maximum dose enhancement of 5-7% was noted for both 6-MV X-rays and 60Co for beams incident on the surface containing the THORP plate segment, whereas beams incident on the opposite surface induced only a very small dose enhancement (2-3%). CONCLUSION: Using a new experimental model, TLD measurements showed only marginally significant dose variations at bone/titanium interfaces around THORP screws, all measured values being very close to the uncertainty limits (+/- 5%) associated with the method. For both 60Co and 6-MV beams, dose variations appeared smaller for axial than for perpendicular incidences. Because photon beams used in head and neck cancer treatment are most often directed parallel to the screw axes, these results suggest that failures of prosthetic osseointegration are unlikely to be explained by an overdosage at the bone/titanium interface.
PURPOSE: Measurements of internal organ motion have demonstrated that daily organ deformation exists throughout the course of radiation treatment. However, a method of constructing the resultant dose delivered to the organ volume remains a difficult challenge. In this study, a model to quantify internal organ motion and a method to construct a cumulative dose in a deforming organ are introduced. METHODS AND MATERIALS: A biomechanical model of an elastic body is used to quantify patient organ motion in the process of radiation therapy. Intertreatment displacements of volume elements in an organ of interest is calculated by applying an finite element method with boundary conditions, obtained from multiple daily computed tomography (CT) measurements. Therefore, by incorporating also the measurements of daily setup error, daily dose delivered to a deforming organ can be accumulated by tracking the position of volume elements in the organ. Furthermore, distribution of patient-specific organ motion is also predicted during the early phase of treatment delivery using the daily measurements, and the cumulative dose distribution in the organ can then be estimated. This dose distribution will be updated whenever a new measurement becomes available, and used to reoptimize the ongoing treatment. RESULTS: An integrated process to accumulate dosage in a daily deforming organ was implemented. In this process, intertreatment organ motion and setup error were systematically quantified, and incorporated in the calculation of the cumulative dose. An example of the rectal wall motion in a prostate treatment was applied to test the model. The displacements of volume elements in the rectal wall, as well as the resultant doses, were calculated. CONCLUSION: This study is intended to provide a systematic framework to incorporate daily patient-specific organ motion and setup error in the reconstruction of the cumulative dose distribution in an organ of interest. The realistic dose distribution in an organ of interest gives the true dose-volume relationship, and may play an important role in the evaluation of the dose response of human organs. Dose reconstruction during the course of treatment delivery can also be used as an important feedback for the online optimization of individual treatment plans.
A megavoltage computed tomography (MVCT) system was developed on the University of Wisconsin tomotherapy benchtop. This system can operate either axially or helically, and collect transmission data without any bounds on delivered dose. Scan times as low as 12 s per slice are possible, and scans were run with linac output rates of 100 MU min(-1), although the system can be tuned to deliver arbitrarily low dose rates. Images were reconstructed with clinically reasonable doses ranging from 8 to 12 cGy. These images delineate contrasts below 2% and resolutions of 3.0 mm. Thus, the MVCT image quality of this system should be sufficient for verifying the patient's position and anatomy prior to radiotherapy. Additionally, synthetic data were used to test the potential for improved MVCT contrast using maximum-likelihood (ML) reconstruction. Specifically, the maximum-likelihood expectation-maximization (ML-EM) algorithm and a transmission ML algorithm were compared with filtered backprojection (FBP). It was found that for expected clinical MVCT doses enough imaging photons are used such that little benefit is conferred by the improved noise model of ML algorithms. For significantly lower doses, some quantitative improvement is achieved through ML reconstruction. Nonetheless, the image quality at those lower doses is not satisfactory for radiotherapy verification.
The use of radiation beam attenuators led to radiation injury of the spinal cord in one patient and of the peripheral nerve in another due to unsuspected large-fraction irradiation. The anatomic distribution of radiation dose was reconstructed in the sagittal plane for the patient who developed radiation myelopathy and in the axial plane for the patient who developed peripheral neuropathy. The actual dose delivered to the injured structure in each patient was taken from the dose distribution and recorded along with the time, number of fractions, and dose per fraction. The patient who developed radiation myelopathy received a total of 46.5 Gy in twenty-three 2.1 Gy fractions in 31 days to the upper cervical spinal cord where the thickness of the neck was less than the central axis thickness due to cervical lordosis and absence of a posterior compensating filter. The patient who developed peripheral neuropathy received 55 Gy in twenty-five 2.2 Gy fractions in 50 days to the femoral nerve using bolus over the groins and an anterior one-half value layer Cerrobend pelvic block to bias the dose anteriorly. Compensating filters and other beam attenuators should be used with caution because they may result in unsuspected large-fraction irradiation and total doses of radiation that exceed the tolerance of critical structures.
CT-Dose-Index of Standard-CT corresponds to CT-Dose-Effect-Index of Spiral-CT. Spiral-CT provides a continuous data acquisition with well balanced dose profiles. Increasing pitch reduces radiation dose and nevertheless an unbroken reconstruction of scanned volume is possible. In contrast to Standard-CT, small parts at both ends of the volume scan are not reconstructed. Volume-Dose-Index therefore is elevated in short scan times but corresponds to that of Standard-CT in long scan times. 1 mm slices cause more radiation exposure due to their broadened dose profiles.
As scoliosis requires a global and local 3D examination of the spine in standing position, stereoradiography appears as one of the most adequate 3D imaging tool for it diagnosis. Our purpose was to increase the geometry definition of the stereoradiographic reconstruction to obtain morpho-realistic models and to validate them using 41 dry vertebrae. Our results propose 2000 points 3D personalised models without any loss of accuracy in comparison to previous studies.
BACKGROUND: The aim of this randomized clinical trial was to determine whether a single intravenous dose of 2 g flucloxacillin could prevent wound infection after primary non-reconstructive breast surgery. METHODS: The study included 618 patients undergoing local excision (n = 490), mastectomy (n = 107) or microdochectomy (n = 21). Patients were randomized to receive either a single dose of flucloxacillin immediately after the induction of anaesthesia or no intervention. Wound morbidity was monitored by an independent research nurse for 42 days after surgery. RESULTS: The incidence of wound infection was similar in the two groups: 10 of 311 (3.2 percent) in the flucloxacillin group and 14 of 307 (4.6 percent) in the control group (chi(2) = 0.75, P = 0.387; relative risk 0.71, 95 percent confidence interval 0.32 to 1.53). The groups also had similar wound scores and rates of moderate or severe cellulitis. Wound infection presented a median of 16 days after surgery. CONCLUSION: The administration of a single dose of flucloxacillin failed to reduce the rate of wound infection after non-reconstructive breast surgery.