Chapter 7: Description of MISCAN-lung, the Erasmus MC Lung Cancer microsimulation model for evaluating cancer control interventions.

The MISCAN-lung model was designed to simulate population trends in lung cancer (LC) for comprehensive surveillance of the disease, to relate past exposure to risk factors to (observed) LC incidence and mortality, and to estimate the impact of cancer-control interventions. MISCAN-lung employs the technique of stochastic microsimulation of life histories affected by risk factors. It includes the two-stage clonal expansion model for carcinogenesis and a detailed LC progression model; the latter is specifically intended for the evaluation of screenings. This article elucidates further the principles of MISCAN-lung and describes its application to a comparative study within the CISNET Lung Working Group on the impact of tobacco control on U.S. LC mortality. MISCAN-lung yields an estimate of the number of LC deaths avoided during 1975-2000. The potential number of avoidable LC deaths, had everybody quit smoking in 1965, is 2.2 million; 750,000 deaths (30%) were avoided in the United States due to actual tobacco control interventions. The model fits in the actual tobacco-control scenario, providing credibility to the estimates of other scenarios, although considering survey-reported smoking trends alone has limitations.

Dosemeter readings and effective dose to the cardiologist with protective clothing in a simulated interventional procedure.

A personal dosemeter issued for individual monitoring is calibrated in terms of personal dose equivalent, usually H(P)(10). In general it yields a reasonable estimate of effective dose (E) when the exposed person does not wear protective clothing. In interventional cardiology, however, a lead equivalent apron is worn and often a thyroid collar. A correction factor will then be necessary to convert a dosemeter reading to E. To explore this factor an interventional cardiology procedure is simulated based on exposure conditions typical for a modern hospital in the BENELUX area. The dose to the cardiologist is investigated using Monte Carlo simulation of radiation transport. It is concluded that a personal dosemeter may best be worn outside the apron at a central position high on the chest for least dependence on the beam direction. It will overestimate E by roughly a factor of 20 (apron and thyroid collar of 0.25 mm Pb).

Results of a European survey on patient doses in paediatric radiology.

Paediatric patients represent a very specific group within the radiology department. Compared to adult patients, they are more sensitive to radiation. As they are sometimes submitted to several radiology procedures, dose and image quality should be well balanced. Nowadays, only a few centres specialize in paediatric imaging, and knowledge of paediatric patient doses is, therefore, very scattered. The effect of the introduction of digital technology on paediatric patient doses remains largely undocumented. Data collected in the present survey illustrate that there is a clear need for standardisation in this domain. The proposal of a European diagnostic reference level (DRL) is quite difficult. Preliminary DRLs, based on typically 5-7 radiology centres per examination are proposed. The 'effective dose' may or may not be a very rigorous parameter, but it still remains useful nowadays to calculate a parameter that summarises the possible radiation-induced detriment to these young patients. However, conversion factors for calculation of the effective dose should be harmonised. Future studies should include an image quality evaluation study, using criteria that account for digital equipment. Data collection would be straightforward and could be performed in a systematic and automatic way if DICOM headers of digital images would include appropriate as well as relevant information for the particular case of paediatric examinations.

Quality control measurements for fluoroscopy systems in eight countries participating in the SENTINEL EU coordination action.

Quality control (QC) is becoming increasingly important in relation to the introduction of digital medical imaging systems using X rays. It was, therefore, decided to organise and perform a trial on image quality and physical measurements. The SENTINEL toolkit for QC measurements of fluoroscopy systems containing equipment and instructions for their use in the assessment of dose and image quality circulated among participants in the trial. The participants reported on their results. In the present contribution, the impact of the trial on the selected protocols is presented. The Medical Physics and Bioengineering protocol appeared to be useful for QC, and also for digital systems. The protocol needs an additional section, or an addition to each section, to state compliance with the requirements. The circular cross-sections of the Leeds test objects need adaptation for rectangular flat panel detector (FPD) systems. Only one participant was able to perform the monitor test using MoniQA. This is due to the fact that assistance is required from the suppliers of the X-ray systems. This problem needs to be solved to apply MoniQA in practice.

Estimating effective dose for a cardiac catheterisation procedure with single or double personal dosemeters.

In most countries of the European Union legislation requires individual determination and registration of the dose to radiological workers exposed to ionising radiation to check whether dose limits are exceeded. To assess stochastic risk, ideally effective dose (E) should be known. In practice, personal dose equivalent [H(P)(10)] is used as it can be measured with a personal dosemeter. The dosemeter reading may provide a reasonable assessment of H(P)(10), but it may deviate strongly from E, in particular in radiology procedures for medical diagnosis or intervention when protective clothing like lead-equivalent apron and thyroid collar is worn. In the literature various correction factors and algorithms to convert readings of single or dual dosemeters to an estimate of E can be found. An illustrative example of a cardiac catheterisation procedure, in which dose calculations are made by Monte Carlo simulation of radiation transport, shows that such corrections may still yield considerable overestimation.

The contribution of residual leukemic cells in the graft to leukemia relapse after autologous bone marrow transplantation: mathematical considerations.

A hypothetical model for estimating the probability of leukemia development, supported by experimental evidence, provides a basis on which the conclusion can be drawn that residual leukemic cells in the graft will not contribute significantly to the occurrence of a leukemia relapse after autologous bone marrow transplantation.

Monitoring of leukemia growth in a rat model using a highly sensitive assay for the detection of LacZ marked leukemic cells.

A very sensitive assay for the detection of LacZ marked cells of an in vitro growing subline of the brown Norway rat myelocytic leukemia (BNML) model was developed. By combining cytochemical X-gal staining with D-galactose mediated suppression of endogenous background beta-galactose activity, a detection sensitivity of one leukemic cell per 10(8) normal bone marrow cells could be achieved. A detailed analysis of the in vivo growth pattern and kinetics of this cell line is presented. Also, it is shown that after cyclophosphamide treatment of leukemic rats no leukemic colonies are formed in an agar-colony assay, whereas the leukemic cells remain detectable in the bone marrow for a considerable time period. Eventually, however, all leukemic cells disappear from the marrow. These findings are discussed in the light of prolonged detection of rare leukemic cells in patients in continuing remission.

Dose conversion coefficients for interventional procedures.

Effective dose (E) is a convenient quantity to estimate the stochastic risk of radiation applied to patients in interventional procedures and can be used for optimisation. Relatively long exposure times may cause deterministic effects. Hence it is necessary to know the (maximum local) doses in organs owing to the interventional procedure. In practice, organ doses cannot be measured directly. They are derived by applying a conversion coefficient to a measurable quantity, e.g. dose-area product (DAP) or entrance skin dose. For a number of interventional procedures, dose conversion coefficients (DCCs) can be found in the literature. Various DCCs are stated for nominally equal procedures, e.g. for percutaneous transluminal coronary angioplasty both 0.18 and 0.27 mSv Gy(-1) cm(-2) were reported to convert DAP to effective dose. Dependence of DCC on protocol and equipment parameters, as demonstrated through Monte Carlo simulation in this paper, makes it hazardous to simply adopt a literature value.

Optimisation strategies and justification: an example in uterine artery embolisation for fibroids.

Radiation risk has to be justified and optimised. This study discusses the radiation risk of uterine artery embolisation (UAE) for the treatment of fibroids. A total of 70 consecutive UAE dosimetry parameters were assessed. Using Monte Carlo simulation, organ and effective doses and dose conversion coefficients (DCCs) (mSv Gy cm(-2)) were calculated. During UAE optimisation, avoidance of oblique views and use of last-image-hold (LIH) documentation instead of digital subtraction angiography (DSA) were investigated. Mean dose-area product (DAP) was 37.1 Gy cm2 (median 23.7 Gy cm2) and mean fluoroscopy time was 18.4 min (median 16.6 min). Dose values decreased as the study progressed: mean DAP for patients 1-21, 68.5 Gy cm2; patients 22-43, 35.7 Gy cm2; and patients 44-69, 13.0 Gy cm2. Average DCC for DSA image procedures was 0.572, yielding a mean effective dose of 29.6 mSv (median 17.1 mSv). For LIH-only procedures, an average DCC of 0.813 was estimated [using mean effective dose: 10.6 mSv (median 8.1 mSv)].

Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate in plasma and bone marrow of children receiving low-dose oral methotrexate.

The absorption, distribution, and elimination kinetics of low-dose p.o. methotrexate (MTX) were repeatedly studied in 19 children during maintenance treatment of childhood acute lymphoblastic leukemia. Plasma concentrations, urinary elimination, and bone marrow concentrations of MTX and 7-hydroxymethotrexate (7-OH-MTX) were monitored during 24 h following a routine p.o. dose (30 mg/m2) using high-pressure liquid chromatography. Significant interindividual variability was found in time to peak concentration (30-180 min), peak concentration (0.41-2.77 microM), and to a lesser extent the half-lives (t1/2 alpha: 32.8-86.1 min; t1/2 beta: 43.6-350.0 min; t1/2 absorption: 25.2-60.3 min) and plasma area under the concentration-time curve from zero to infinity (195.6-818.5 microM.min). Significant amounts of 7-OH-MTX were detected in plasma, with a mean area under the concentration-time curve from zero to infinity of 208 microM.min compared with 365.6 microM.min for MTX. High concentrations of 7-OH-MTX were present in bone marrow 24 h after oral MTX (15/19 patients) and were at least five fold those in plasma and three fold the concentration of MTX in bone marrow. In four patients occasionally neither MTX nor metabolite could be detected. Repeated examination of these pharmacokinetic parameters in plasma and bone marrow showed that the intraindividual variability was small.

Patient dosimetry in abdominal arteriography.

This study aims at accurate quantification of x-ray exposure and effective dose to the patient in abdominal arteriography. Using an automatic monitoring system, all relevant exposure parameters were determined during 172 abdominal arteriographies. Common projections were extracted for a 'normal' reference group of procedures and used in Monte Carlo calculations of dose-area product to organ dose conversion coefficients. Dose-area product, organ doses and effective dose were quantified for intravenous and intra-arterial procedures. The large data sets describing exposure could be condensed to a set of 28 common views. New coefficients to convert dose area product to organ equivalent dose and effective dose were calculated for nine views contributing approximately 80% to the total dose-area product. The average dose-area product was 32 Gy cm2 in intravenous procedures and 47 Gy cm2 in intra-arterial procedures. The corresponding average effective doses to the patient were 4 mSv and 6 mSv respectively (range 2-12 mSv, actual value depending on procedure type and gender). It is concluded that automatic monitoring of x ray exposure parameters, complemented by the calculation of Monte Carlo organ dose conversion coefficients, is a feasible and promising approach to accurate dosimetry of complex arteriographic procedures.

Calculation of dose conversion factors for posterior-anterior chest radiography of adults with a relatively high-energy X-ray spectrum.

In a survey of X-ray units as applied for thorax examinations considerable variations were observed in entrance dose among different hospitals in the Leyden region. For the median exposure conditions, i.e. 125 kVp, heavy filtering and large focus-to-skin distance (177.5 cm), absorbed dose distributions have been derived using mathematical phantoms of a standard male or female adult. For relatively high-energy X-rays, back scatter factors were calculated by Monte Carlo simulation. In addition, conversion factors were obtained, relating organ doses to air kerma, free in air. Effective dose equivalent and effective dose were calculated according to ICRP-26 and ICRP-60 recommendations, respectively. The computational procedures were compared with results reported in the literature for a similar exposure configuration but using lower-energy X-rays. Causes of relative differences ranging from -56% to +34% were analysed. In addition to the photon energy spectrum and filtering, the exposure geometry appears to be a very important parameter which can be optimized for the purpose of dose reduction.

Monte Carlo calculations for assessment of radiation dose to patients with congenital heart defects and to staff during cardiac catheterizations.

Effective dose is an important quantity in relation to assessment of radiation risk. Organ and effective doses to paediatric patients undergoing diagnostic and therapeutic heart catheterization procedures can be assessed by combining relatively simple measurements, e.g. of dose-area product (DAP), and calculated dose conversion factors (DCF). This also holds for the radiation dose to the hospital staff, e.g. the cardiologist. Monte Carlo (MC) simulation of radiation transport in mathematical anthropomorphic phantoms is used to obtain the DCFs, which strongly depend on beam quality and geometrical parameters. The performance of a dedicated fast MC code (PCXMC) for patient dosimetry is compared with that of a more elaborate general purpose MC code (MCNP). Resulting organ doses sometimes may differ considerably, partly due to phantom differences. While MCNP uses separate male and female mathematical phantoms, PCXMC uses a hermaphrodite. However, both codes yield effective doses that agree rather well, so PCXMC can be used for convenience. The MCNP code is used to calculate the effective dose to the cardiologist exposed to radiation scattered from the patient. Without protective clothing, effective dose per procedure to the cardiologist is at least two orders of magnitude lower than that to the patient. The effectiveness of various types and thickness of protective clothing has been evaluated for one view of one cardiac catheterization. The results of the calculations do not contradict experimental studies from the literature. MC simulation may serve as a useful tool to improve the accuracy of estimating occupational effective dose from personal dose monitors.

Calculation of computed tomography dose index to effective dose conversion factors based on measurement of the dose profile along the fan shaped beam.

The variation in computed tomography dose index (CTDI) to effective dose conversion factors between different types of CT scanner is large (i.e. a factor of about 2 due to differences in beam shaping filters). Consequently, scanner specific conversion factors have to be applied. For some types of scanner, however, detailed information on the construction of beam shaping filters is not provided by the manufacturers. It is of interest to investigate the use of measured dose profiles for the calculation of conversion factors. Based upon measured dose profiles, two appropriate photon spectra selected on the basis of measured half value layers, gender specific adult phantoms Adam and Eva, and the Monte Carlo neutron and photon radiation transport code (MCNP), organ and effective dose conversion factors are calculated. To validate the method, a comparison is made between results for measured and calculated beam profiles for a Philips Tomoscan 350. The results in terms of effective dose per slice per unit of CTDI are compared with published data. Relative difference in conversion factors per slice averaged over all slices used for the calculations is 13 +/- 4% between the two spectra, 10.2 +/- 0.2% between measured and calculated beam profiles and 50 +/- 191% between the phantoms of different gender. The relative difference between the averaged results for the Adam and Eva phantoms and published results for a hermaphrodite phantom is on average equal to or less than 15 +/- 13%, depending on the spectrum and beam profile used, although larger differences can occur for specific slices. It is concluded that CTDI to effective dose conversion factors can be derived on the basis of measured beam profiles.

Radiation burden to paediatric patients due to micturating cystourethrography examinations in a Dutch children's hospital.

Micturating cystourethrography (MCU) examinations of paediatric patients in a major Dutch children's hospital (JKZ) were evaluated to generate quantitative information on effective dose (E). A standard examination involves three radiographs plus fluoroscopy. Observed total dose-area product (DAP) for 84 children increased, on average, with increasing age class from 0.2 to 2.2 Gy cm2. In 11 cases, separate DAP per view was measured; enabling determination, per view, of organ (CF) and effective (CE) dose conversion factors, i.e. dose per unit of DAP. Monte Carlo simulation of photon transport in male and female mathematical phantoms was applied for newborn, 1 year, 5 year, 10 year and 15-year-old patients, and interpolated for other ages. CE per view decreases with increasing age class, yielding about a factor of 10 difference between the extremes of the range. Female values are usually some 20-30% above male ones. CE for one of the views appeared to be representative for the complete examination and was used to estimate total E for each patient. Averaged per age class, E remains approximately constant at 0.3-0.4 mSv, although a tendency to increase with increasing age exists, for females in particular. Within an age class, individual patients may differ in E by a factor of two up to six. Stomach, lower large intestine, bladder wall, liver and ovaries receive relatively high doses. Compared with published data and DAP measured in a few other Dutch hospitals, the radiation burden of MCU is low at the JKZ. This indicates a good degree of optimization with respect to radiation protection (e.g. modern equipment, increased tube voltage, fast film-screen combination).

Patient and staff radiation dose in fluoroscopy-guided TIPS procedures and dose reduction, using dedicated fluoroscopy exposure settings.

Fluoroscopy guided interventions, such as transjugular intrahepatic portosystemic shunt (TIPS) procedures, can results in relatively high radiation doses to patients and staff. The purpose of this study was to evaluate the possible benefit of dedicated fluoroscopy exposure factors in the reduction of doses. Doses to patients and staff were measured during fluoroscopy-guided TIPS procedures in two Dutch university hospitals. Patient doses were calculated from dose-area product (DAP) measurements, entrance beam dimensions and DAP conversion factors. Staff doses were measured outside lead aprons using electronic personal dosemeters. Average patient entrance skin dose (ESD) rate during fluoroscopy was 49 mGy min-1 (13 cases, average fluoroscopy duration 32 min) in one hospital, and 6 mGy min-1 (10 cases, average fluoroscopy duration 50 min) in the other. Estimated staff effective dose per procedure was 28 microSv average in the first hospital compared with 4 microSv average in the other. The use of dedicated fluoroscopy exposure factors, with a relatively high tube voltage and lower tube current resulted in a significant dose reduction for patient and staff in this type of radiological intervention.

A comparison of patient dose for examinations of the upper gastrointestinal tract at 11 conventional and digital X-ray units in The Netherlands.

The objective of this study was to derive the effective dose to patients from examinations of the upper gastrointestinal (GI) tract at 11 X-ray units in 10 Dutch hospitals. Entrance dose and entrance dose rate were measured at the surface of a homogeneous PMMA phantom and at the entrance surface of the image intensifier. Dose-area products (DAPs) were assessed during examinations of patients. The patients (334 females and 256 males) ages were 18-95 years (average 52 years). Effective dose was assessed from DAP using Monte Carlo computer calculations for male and female mathematical anthropomorphic phantoms. The DAPs measured during the survey showed substantial variations, i.e. an overall average value of 21 Gy cm2 and a range of average DAP per X-ray unit varying from 7 to 56 Gy cm2. Variations in the number of images (8-28) and the fluoroscopy time (1.7 min-7.0 min) were also large. A DAP to effective dose conversion factor of 0.32 mSv Gy cm-2 was derived for upper GI studies. The dose survey yielded an overall average effective dose of 6.7 mSv. At one location an examination involving as many as 28 projections was performed, whilst maintaining a DAP well below 15 Gy cm2 and an effective dose below 6 mSv. This was achieved using modern equipment (i.e. high frequency generator, digital spot films) with 0.2 mm additional copper filtration and a relatively high tube voltage. For examinations of the upper GI tract, the application of a reference value of 30 Gy cm2 for the DAP will ensure that, in general, the effective dose to individual patients will not exceed 15 mSv.

Patient and occupational dosimetry in double contrast barium enema examinations.

A new and relatively simple method is presented to distribute total dose-area product (DAP) over a number of projections that model exposure during double contrast barium enema (DCBE) examinations. In addition, hitherto unavailable entrance and effective doses to the physician performing the DCBE examination have been determined. DAP, fluoroscopy time, number of images as well as some patient data were collected for 150 DCBE examinations. For a subset of 50 examinations, the distribution of DAP over 12 hypothetical but representative projections was estimated by measuring the entrance dose in the centre of each of these projections during the complete procedure. Effective dose to the patient was obtained using DAP to effective dose conversion coefficients calculated for each of the 12 projections. Exposure of the worker was quantified by measuring the entrance dose at the forehead, neck, arms, right hand and legs. The sex-averaged effective dose to the patient per examination was 6.4+/-2.1 mSv (mean+/-SD; n=50) and the corresponding DAP was 44+/-22 Gy cm(2). The effective dose to the worker per examination was 0.52 microGy (n=50), whereas the highest entrance dose of 30+/-25 microGy was found for the right arm. The proposed method for deriving the distribution of total DAP over a set of representative projections is much less time consuming than visual observation of patient exposure, whilst accuracy seems acceptable. Entrance and effective doses per examination for workers in DCBE examinations are very low. For a normal workload, doses remain far below the legally established dose limits.

The effect of equipment set up on patient radiation dose in conventional and CT angiography of the renal arteries.

Patient radiation dose in angiography of the renal arteries was assessed and optimized after installing new radiological equipment. In three separate studies (n=50, 25 and 20) patient exposure was monitored in detail. For the first study default factory settings were used, for the second the number of digital subtraction angiography (DSA) images was halved and the X-ray beam filtering during fluoroscopy was increased, and for the third study filtering during DSA was increased as well. Standard projections were derived and used in Monte Carlo simulations to derive dose conversion coefficients to calculate effective dose from the dose-area product (DAP). Dose conversion coefficients were also calculated for CT angiography (CTA). Using default factory settings on the new angiography system, DAP, number of images and effective dose were much higher than on the replaced unit. For the studies given above, DAP was reduced from 144 Gy cm(2) to 65 Gy cm(2) to 32 Gy cm(2), and effective dose from 22 mSv to 11 mSv to 9.1 mSv, respectively. Effective dose due to CTA was 5.2 mSv. It is concluded that modern angiography systems, resulting in high customer satisfaction, may readily cause much higher patient exposure than older systems. These doses may also be much higher than necessary. Optimization before putting such systems into use is absolutely essential. Internationally accepted recommendations for image quality and technique factors in angiography would be of great help.

PCDOSE: an interactive software system to calculate internal radiation dose on a personal computer.

An interactive, menu directed, software system to calculate committed dose equivalents for individuals with different physiques after inhalation, ingestion or injection of radionuclides has been developed. The calculations are based on ICRP 26/30 methods. The programs are written in PASCAL and can be implemented on a personal computer with a MS-DOS operating system and a hard disk with a storage capacity of at least 20 Mb. This paper describes the development and features of the system.