Two-step validation of a Monte Carlo dosimetry framework for general radiology.

The Monte Carlo technique is considered gold standard when it comes to patient-specific dosimetry. Any newly developed Monte Carlo simulation framework, however, has to be carefully calibrated and validated prior to its use. For many researchers this is a tedious work. We propose a two-step validation procedure for our newly built Monte Carlo framework and provide all input data to make it feasible for future related application by the wider community. The validation was at first performed by benchmarking against simulation data available in literature. The American Association of Physicists in Medicine (AAPM) report of task group 195 (case 2) was considered most appropriate for our application. Secondly, the framework was calibrated and validated against experimental measurements for trunk X-ray imaging protocols using a water phantom. The dose results obtained from all simulations and measurements were compared. Our Monte Carlo framework proved to agree with literature data, by showing a maximal difference below 4% to the AAPM report. The mean difference with the water phantom measurements was around 7%. The statistical uncertainty for clinical applications of the dosimetry model is expected to be within 10%. This makes it reliable for clinical dose calculations in general radiology. Input data and the described procedure allow for the validation of other Monte Carlo frameworks.

The simulation of 3D microcalcification clusters in 2D digital mammography and breast tomosynthesis.

PURPOSE: This work proposes a new method of building 3D models of microcalcification clusters and describes the validation of their realistic appearance when simulated into 2D digital mammograms and into breast tomosynthesis images. METHODS: A micro-CT unit was used to scan 23 breast biopsy specimens of microcalcification clusters with malignant and benign characteristics and their 3D reconstructed datasets were segmented to obtain 3D models of microcalcification clusters. These models were then adjusted for the x-ray spectrum used and for the system resolution and simulated into 2D projection images to obtain mammograms after image processing and into tomographic sequences of projection images, which were then reconstructed to form 3D tomosynthesis datasets. Six radiologists were asked to distinguish between 40 real and 40 simulated clusters of microcalcifications in two separate studies on 2D mammography and tomosynthesis datasets. Receiver operating characteristic (ROC) analysis was used to test the ability of each observer to distinguish between simulated and real microcalcification clusters. The kappa statistic was applied to assess how often the individual simulated and real microcalcification clusters had received similar scores ("agreement") on their realistic appearance in both modalities. This analysis was performed for all readers and for the real and the simulated group of microcalcification clusters separately. "Poor" agreement would reflect radiologists' confusion between simulated and real clusters, i.e., lesions not systematically evaluated in both modalities as either simulated or real, and would therefore be interpreted as a success of the present models. RESULTS: The area under the ROC curve, averaged over the observers, was 0.55 (95% confidence interval [0.44, 0.66]) for the 2D study, and 0.46 (95% confidence interval [0.29, 0.64]) for the tomosynthesis study, indicating no statistically significant difference between real and simulated lesions (p > 0.05). Agreement between allocated lesion scores for 2D mammography and those for the tomosynthesis series was poor. CONCLUSIONS: The realistic appearance of the 3D models of microcalcification clusters, whether malignant or benign clusters, was confirmed for 2D digital mammography images and the breast tomosynthesis datasets; this database of clusters is suitable for use in future observer performance studies related to the detectability of microcalcification clusters. Such studies include comparing 2D digital mammography to breast tomosynthesis and comparing different reconstruction algorithms.

Evaluation of clinical image processing algorithms used in digital mammography.

Screening is the only proven approach to reduce the mortality of breast cancer, but significant numbers of breast cancers remain undetected even when all quality assurance guidelines are implemented. With the increasing adoption of digital mammography systems, image processing may be a key factor in the imaging chain. Although to our knowledge statistically significant effects of manufacturer-recommended image processings have not been previously demonstrated, the subjective experience of our radiologists, that the apparent image quality can vary considerably between different algorithms, motivated this study. This article addresses the impact of five such algorithms on the detection of clusters of microcalcifications. A database of unprocessed (raw) images of 200 normal digital mammograms, acquired with the Siemens Novation DR, was collected retrospectively. Realistic simulated microcalcification clusters were inserted in half of the unprocessed images. All unprocessed images were subsequently processed with five manufacturer-recommended image processing algorithms (Agfa Musica 1, IMS Raffaello Mammo 1.2, Sectra Mamea AB Sigmoid, Siemens OPVIEW v2, and Siemens OPVIEW v1). Four breast imaging radiologists were asked to locate and score the clusters in each image on a five point rating scale. The free-response data were analyzed by the jackknife free-response receiver operating characteristic (JAFROC) method and, for comparison, also with the receiver operating characteristic (ROC) method. JAFROC analysis revealed highly significant differences between the image processings (F = 8.51, p < 0.0001), suggesting that image processing strongly impacts the detectability of clusters. Siemens OPVIEW2 and Siemens OPVIEW1 yielded the highest and lowest performances, respectively. ROC analysis of the data also revealed significant differences between the processing but at lower significance (F = 3.47, p = 0.0305) than JAFROC. Both statistical analysis methods revealed that the same six pairs of modalities were significantly different, but the JAFROC confidence intervals were about 32% smaller than ROC confidence intervals. This study shows that image processing has a significant impact on the detection of microcalcifications in digital mammograms. Objective measurements, such as described here, should be used by the manufacturers to select the optimal image processing algorithm.

Typetesting of physical characteristics of digital mammography systems for screening within the Flemish breast cancer screening programme.

To investigate compliance with the acceptance criteria of the European guidelines for quality assurance in breast cancer screening, a typetesting programme of the physical characteristics of digital mammography systems based on direct readout (DR) technology or computed radiography (CR) was organised and executed within the Flemish breast cancer screening programme. While in general image quality/dose characteristics of flat panel DR systems passed the acceptance criteria more easily than CR systems, the slit-scanning direct photon counting system included in present study was outstanding in combining a very low dose with a good image quality. The data obtained up to now indicate the necessity of retuning the AEC for DR systems according to constant contrast to noise ratio (CNR) over the whole range of PMMA thicknesses (20-70 mm) to improve image quality in imaging breasts of large thickness at the cost of higher doses. For the two CR systems which passed the typetesting procedure dose levels do not allow a similar improvement of CNR for thick objects for these systems. The obtained results highlight the importance of the use of high Z target/filter combinations in X-ray generating systems for imaging thick objects to meet the image quality/dose criteria. With respect to image display aspects high-quality 3-megapixel LCD monitors succeeded also in the typetesting procedure in addition to 5-megapixel monitors. However, as zooming and scrolling are necessary for 3-megapixel monitors to get the full resolution capabilities of the image capture system, 5-megapixel monitors are preferred in a busy screening environment.

An improved method for simulating microcalcifications in digital mammograms.

The assessment of the performance of a digital mammography system requires an observer study with a relatively large number of cases with known truth which is often difficult to assemble. Several investigators have developed methods for generating hybrid abnormal images containing simulated microcalcifications. This article addresses some of the limitations of earlier methods. The new method is based on digital images of needle biopsy specimens. Since the specimens are imaged separately from the breast, the microcalcification attenuation profile scan is deduced without the effects of over and underlying tissues. The resulting templates are normalized for image acquisition specific parameters and reprocessed to simulate microcalcifications appropriate to other imaging systems, with different x-ray, detector and image processing parameters than the original acquisition system. This capability is not shared by previous simulation methods that have relied on extracting microcalcifications from breast images. The method was validated by five experienced mammographers who compared 59 pairs of simulated and real microcalcifications in a two-alternative forced choice task designed to test if they could distinguish the real from the simulated lesions. They also classified the shapes of the microcalcifications according to a standardized clinical lexicon. The observed probability of correct choice was 0.415, 95% confidence interval (0.284, 0.546), showing that the radiologists were unable to distinguish the lesions. The shape classification revealed substantial agreement with the truth (mean kappa = 0.70), showing that we were able to accurately simulate the lesion morphology. While currently limited to single microcalcifications, the method is extensible to more complex clusters of microcalcifications and to three-dimensional images. It can be used to objectively assess an imaging technology, especially with respect to its ability to adequately visualize the morphology of the lesions, which is a critical factor in the benign versus malignant classification of a lesion detected in screening mammography.

Preliminary validation of a new variable pattern for daily quality assurance of medical image display devices.

This paper reports on a comparative study between the well-established test patterns for daily quality assurance (QA) of monitors of the American Association of Medical Physicists, Task Group 18 (AAPMtg18) and the Deutsches Institut für Normung e.V (DIN), and a newly proposed variable test pattern. A characteristic of the test patterns currently used for the QA of monitors is their static nature: The same test pattern is always used. This enables a learning effect that may bias the results over time. To address this problem we have developed a variable pattern for the quality assurance of monitors (MoniQA) that allows an evaluation of contrast visibility, geometric distortion, resolution, global image quality including uniformity, and artifacts. The test pattern includes randomly generated elements intended to prevent the observer from learning the test. Examples are random characters that have to be discriminated from the background to evaluate the threshold luminance difference and variable positions of different features in the test pattern. The newly proposed test patterns were generated and visualized on different viewing stations with a software tool developed in JAVA. In this study, we validated these patterns against the well-known AAPMtg18 and DIN test patterns on 22 monitors. The results showed that the MoniQA test can indicate the same monitor problems as the other well-known patterns and is significantly quicker to evaluate than the AAPMtg18 test patterns. The MoniQA pattern is a promising alternative for daily quality control of medical viewing stations.

Molecular Structures of Sulfur Cyanide Trifluoride, SF(3)CN, and Sulfinyl Cyanide Fluoride, FS(O)CN.

General valence force fields for SF(3)CN and FS(O)CN are derived from vibrational data taken from the literature and from theoretical calculations. Gas phase electron diffraction studies on both molecules yield the following geometric parameters (r(a) distances and angles with 3sigma uncertainties). SF(3)CN: r(S-F(e)) = 155.2(4) r(S-F(a)) = 165.7(3), r(S-C) = 173.6(8), r(C&tbd1;N) = 115.9(4) pm; angle(F(a)SF(e)) = 86.9(3), angle(F(a)SC) = 86.0(4) angle(F(e)SC) = 98.7(8), angle(F(a)SF(a)) = 169.0(6), angle(SCN) = 171(4) degrees. FS(O)CN: r(S-F) = 159.8(3), r(S=O) = 143.2(2), r(S-C) = 178.3(3), r(C&tbd1;N) = 115.0(3) pm; angle(FSO) = 104.9(4), angle(FSC) = 93.9(4), angle(CSO) = 105.3(5), angle(SCN) = 176(4) degrees. These experimental results are compared to ab initio values (HF/3-21G, HF/6-31G, and MP2/6-31G), and the bonding properties in these sulfur (IV) cyanides are discussed.

Cooperation, optimal density and low density thresholds: yet another modification of the logistic model.

A modification of the logistic model is proposed which incorporates the principles of optimal density and cooperation. Three components have been added defining effectivity, "saturation" and exponentiality of cooperation. By adequate choice of constants a wide array of population characteristics may be represented including threshholds of growth. The main application of the model concerns, low density problems such as colonization and extinction.

Differences among genotypic frequencies of undisturbed and manipulated populations of Daphnia.

A lake population of Daphnia, and several subpopulations in large plastic enclosures within the lake and manipulated with respect to population densities and nutrient enrichment (acetate, nitrate, phosphate), exhibited differences among genotypic frequencies at the phosphoglucoisomerase locus. The lake and control populations exhibited similar genotypic frequencies which were significantly different from those found in the three manipulated populations. The similarity of the genetic reaction in the manipulated populations may be related to similarity of manipulation. All populations exhibited deviations from Hardy-Weinberg proportions in the form of heterozygote excess.

Coexistence of similar zooplankton species by differential adaptation to reproduction and escape in an environment with fluctuating food and enemy densities : III. Laboratory experiments.

(1) Daphnia hyalina (H) and D. cucullata (C) have coexisted for at least 50 years in the prealpine Klostersee, Federal Republic of Germany. On the basis of field data it was hypothesized that coexistence is facilitated by a compensatory mechanism: H would be a better reproducer but worse escaper than C. This would produce an advantage for H whenever reproduction is higher than mortality due to predation. C would dominate when mortality outweighs reproduction. To test this hypothesis, a number of experiments on growth, reproduction, mortality by fish predation, and competition were performed. (2) At 15° C, equivalent developmental stages were larger in H than in C. H grew faster, its growth slowed down later, and it lived longer (Fig. 2). Brood intervals were slightly shorter and both the number of eggs per brood and the total number of broods were much greater in H than in C (Fig. 3). On the other hand, generation time (time from birth to the release of the first clutch of eggs) was longer in H than in C (Figs. 2 and 4). (3) Intrinsic rates of natural increase were calculated from the growth data of the individuals by the method of Edmondson (1968). If both species are allowed to grow and reproduce to their maximal sizes, H is about 20% better than C. The major contribution to population growth comes from the first three to four broods. By artificially modifying the data on (a) the maximal age of the mothers, (b) the maximal size of the mothers, (c) the brood size, and (d) the generation time, it can be shown that the maximal size of the mothers has the greatest impact on population growth, and accounts for the greatest differences between the growth rates of both species. Varying the brood size has the smallest effect (Figs. 5 and 6). (4) Predation experiments with minnows (Phoxinus laevis) at 20° C and 500 Lux gave the following results: (a) Starting with unexperienced fish, predation increased during the first weeks of experimentation. After about 10 experiments the fish showed no further trend of improvement (Fig. 7).-(b) The fish preyed over the whole range of prey sizes (500-1500 µ body length) but large prey types were preferred (Fig. 8). Since H is larger than C, more H were eaten than C. When both species were simultaneously exposed to predation, the relation between prey size (body length L) and predation rate m was curvilinear and best described by the equation m∼L2.5-3.5 (Fig. 9).-(c) All size classes of H were eaten faster than equallysized C (Fig. 8). Thus H had a double predation disadvantage. (5) To test the compensatory functions of differential growth and selective predation, competition experiments without decimation, with unselective decimation (by the experimenter), and with selective predation (by fish) were performed at 20° C. (a) Without predation (food as limiting resource) and with unselective decimation (near-exponential growth, food not limiting), H outcompeted C very fast (Fig. 10, curves 1 and 2). This was mainly due to a marked depression of the growth rate of C (Table 3).-(b) Selective predation was a powerful antagonist of differential reproduction (Fig. 11). Selective predation slowed down the displacement of C and there was a tendency of stabilization at 80% H (Fig. 10, curves 3-5).-(c) With selective predation, the growth rates of both species were depressed, probably because predation, the growth rates of both species were depressed, probably because larger and egg-bearing individuals were preferentially eliminated (Table 3).-(d) The slower displacement of C in the face of predation had two causes, first, a greater mortality of H by selective predation, and second, a stronger decrease of the growth rate of H, probably due to the selective elimination of the largest reproducing individuals (Table 3).-(e) There was a marked and significant decrease of log r H/r C (growth advantage of H) during the course of the experiments. This could account for the observed trend toward stabilization. (6) The relevance of the experiments for the interpretation of field data and evolutionary aspects of coexistence are discussed.

Coexistence of similar zooplankton species by differential adaptation to reproduction and escape, in an environment with fluctuating food and enemy densities. I. A model.

A model is presented explaining the coexistence of similar planktonic species that compete for identical food resources and are exposed to identical enemies. The model is based on alternative adaptations of the competitors to reproduction and escape, in an environment that fluctuates with respect to food and enemy densities. Seasonal fluctuations of food and enemies may lead to seasonal segregation of the competitors. Indifferent and stable equilibria are discussed, including the role of abundance-dependent selectivity by predators.

Coexistence of similar zooplankton species by differential adaptation to reproduction and escape in an environment with fluctuating food and enemy densities : II. Field data analysis of Daphnia.

1. In the Klostersee in southern Federal Republic of Germany, Daphnia hyalina (H) and D. cucullata (C) have coexisted for at least 50 years. in 1971/72 they exhibited seasonal density fluctuations which are in accord with predictions from a model based on alternative adaptations of two competitors to natality (food utilization) and mortality (escape from enemies) in an environment that fluctuates with respect to food and intensity of predation. 2. In general, both species fluctuate in a similar fashion. Birth (b), death (m) and growth rates (r) are correlated between both species. Furthermore, in either species birth and death rates are positively correlated. But the birth and death rates of H are about 1.7 times as large as those of C, resulting in stronger density fluctuations of H. This fact, in combination with the seasonal course of the b/m-ratio produces a marked seasonal segregation of the abundances of both species, with H dominating in early summer and C dominating in autumn and winter. 3. In both species, the fluctuations of the growth rate are mainly determined by fluctuations of the death and not the birth rate. 4. Birth and death rates are much higher in the warm season than in the cold season, but births dominate in the cold, deaths in the warm season. Evidence is presented that mortality is mainly due to predation by fish. 5. The differences of natality and mortality which cause the seasonal segregation between the two species, exist independent of seasonal temperature fluctuations. But, there is an additional temperature effect accentuating the differences. 6. A partial correlation analysis shows that by measuring the density of one species and lake temperature, the density difference between both species and, hence, the density of the second species can be predicted with good precision. 7. The importance of the observed temporal segregation and other factors for the stabilized coexistence of both species is discussed.

Quantitative measurement of food selection : A modification of the forage ratio and Ivlev's electivity index.

The forage ratio and Ivlev's electivity index are common measures to quantify food selection but the values of both indices depend not only on the extent of selection but also on the relative abundances of the food types in the environment. They are therefore useless when food types with different relative abundances are compared, or when the relation between selection and relative abundance is studied. Modified versions of both indices are proposed which are based directly on the rates of decrement (mortality) of the food due to feeding, and are independent of the relative abundance.