[Scientific assessment and regulatory approval of radiological screening examinations in Germany]. / Wissenschaftliche Bewertung und rechtliche Zulassung von radiologischen Früherkennungsuntersuchungen in Deutschland.

BACKGROUND: Radiologic imaging technologies like computed tomography (CT) have the potential to screen for various diseases. The potential benefits of screening are always associated with risks, particularly from the application of ionizing radiation. MATERIALS AND METHODS: The International Basic Safety Standards as well as the Council Directive 2013/59/Euratom have set guidelines for the application of ionizing radiation in early detection which were transposed into the German Radiation Protection Law. Accordingly, the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) approves screening examinations on a generic level, based on a scientific report provided by the German Federal Office for Radiation Protection (BfS), and defines in a federal statutory ordinance which type of screening is permissible for detecting a disease for a particular group of persons and under which conditions. RESULTS: With exception of the mammography screening programme, no radiological examination for the early detection of disease has been approved in Germany to date. However, such screenings are currently being offered in Germany. The BfS is currently conducting a scientific evaluation for lung cancer screening with low-dose CT. CONCLUSIONS: Screening examinations with radiological imaging can only be approved when studies with the highest level of evidence have demonstrated that the benefits outweigh the risks. To translate this favourable benefit-risk balance into general health care, strict requirements for the entire screening process including quality assurance must be defined.

[Frequency and doses of diagnostic and interventional X­ray applications : Trends between 2007 and 2014]. / Häufigkeit und Dosis diagnostischer und interventioneller Röntgenanwendungen : Trends zwischen 2007 und 2014.

BACKGROUND: In Germany, approximately 95% of man-made radiation exposure of the population results from diagnostic and interventional X­ray procedures. Thus, radiation protection of patients in this field of application is of great importance. OBJECTIVE: Quantification and evaluation of current data on the frequency and doses of X­ray procedures as well as temporal trends for the years 2007-2014. MATERIAL AND METHODS: For outpatients the frequency of X­ray procedures was estimated using reimbursement data from health insurances and for inpatients by means of hospital statistics. For the years under review, representative values for the effective dose per X­ray application were determined mainly from data reported by X­ray departments to the competent authorities. RESULTS: In 2014 approximately 140 million X­ray procedures were performed in Germany with some 40% from dental examinations. On average 1.7 procedures per inhabitant and year were almost constantly carried out between 2007 and 2014. Besides dental diagnostics, X­ray examinations of the skeleton and thorax were performed most frequently. The number of computed tomography (CT) examinations increased by approximately 40%. The increase in magnetic resonance imaging (MRI) was even more pronounced with approximately 55% but overall CT examinations were still performed more often than MRI. The doses per X­ray procedure were only slightly reduced, despite the various dose reduction approaches established in recent years; therefore, the mean effective dose per inhabitant increased from approximately 1.4 mSv in 2007 to 1.6 mSv in 2014, mainly due to the increasing frequency of CT examinations. CONCLUSION: The principles of justification and optimization of radiological procedures are to be consistently applied in each individual instance, especially in the case of CT examinations.

Parental and hybrid Daphnia from the D. longispina complex: long-term dynamics in genetic structure and significance of overwintering modes.

In recent decades, hybridization has become a focus of attention because of its role in evolutionary processes. However, little is known about changes in genetic structure within and between parental species and hybrids over time. Here, we studied processes of genetic change in parental species and hybrids from the Daphnia longispina complex (Crustacea, Cladocera) over a period of six years across ten habitats. These cyclical parthenogens respond to fluctuating environments by switching from asexual to sexual reproduction. Importantly, sexually produced diapausing eggs, which resist extreme conditions such as low temperatures and serve as dispersal stages, are produced to a lower extent by hybrids. Long-term microsatellite data revealed clear differences between hybrids and parental species. In hybrids, clonal diversity values were lower, whereas heterozygosity and linkage disequilibrium values were higher compared to parental species. Clonal diversity of hybrids responded to the strength of the winter, with cold winters resulting in few genotypes in the following spring. In time windows when only asexual hybrid females survive, priority effects will favour the establishment of the hybrid offspring before hatchlings from parental diapause eggs can enter the community. The constant high levels of heterozygosity maintained by clonal reproduction in hybrids might lead to their successful establishment over time, when they are able to escape competition from both parental species. Although we found evidence that hybrids diversity depends on fluctuating environments, a direct link between hybrid abundance and the strength of winter was missing. Because of reduced adaptability in clonally reproducing hybrids, multiple factors must contribute to promoting their long-term success in fluctuating environments.

[Dynamic contrast-enhanced computed tomography. Tracer kinetics and radiation hygienic principles]. / Dynamische kontrastverstärkte Computertomographie. Tracerkinetische und strahlenhygienische Grundlagen.

Technical innovations in multislice computed tomography (CT) allow for larger volume coverage in ever shorter scan times. This progress has stimulated the clinical application of dynamic contrast-enhanced (DCE) CT techniques, which offer the possibility to noninvasively characterize tissue microcirculation in terms of well-defined physiological quantities. This educational review imparts to radiologists the essential physiological terms and definitions as well as the basic tracer kinetic concepts required for the analysis of DCE-CT data. In particular, four different approaches are presented and exemplified by the analysis of representative DCE data: the steepest-gradient method, model-free algebraic deconvolution in combination with the indicator-dilution theory, two-compartment modelling and the so-called adiabatic approximation to the homogeneity model. Even though DCE-CT offers substantial methodological and practical advantages as compared to DCE-MRI (magnetic resonance imaging), there are also two serious and interconnected shortcomings: the low contrast enhancement in relation to the noise level and the high exposure of patients to ionizing radiation. These limiting aspects are considered in detail from a radiation hygienic point of view, emphasizing the basic principles of justification and optimization. Clinically established as well as potential future applications of DCE-CT will be presented in a subsequent paper.

[Changes in the "medical research" licensing procedure under the German Radiation Protection Ordinance]. / Neuerungen im Genehmigungsverfahren "Medizinische Forschung" gemäß Röntgen- und Strahlenschutzverordnung.

This publication outlines the "medical research" licensing procedure as specified in the amendment of the German Radiation Protection Ordinance of November 1, 2011. The general licensing requirements for the use of radiation have not been changed by the amendment. Three so-called use restrictions (i. e., dose limits of 10 mSv and 20 mSv, age limit of 50 years) have been modified. They will only apply to healthy volunteers in the future. In addition, there are considerable simplifications with respect to applications and licensing procedures of the Federal Office for Radiation Protection (Bundesamt für Strahlenschutz, BfS) regarding the use of radiation in the newly introduced "accompanying diagnostics" ("Begleitdiagnostik") case group. The newly established, independent panel of experts at the German Radiological Society (Deutsche Röntgengesellschaft, DRG) may provide essential support to principal investigators, qualified physicians and sponsors for differentiating between "medical research" and "health care", the latter not being subject to licensing. An expert statement will be issued by the DRG within four weeks of an inquiry. This consulting service is subject to confidentiality, and is free of charge for inquirers and without any commitment.

[Radiation hygiene in medical X-ray imaging. Part 3: radiation exposure of patients and risk assessment]. / Strahlenhygiene in der medizinischen Röntgenbildgebung : Teil 3: Strahlenexposition des Patienten und Risikobewertung.

The frequency of X-ray examinations in Germany and the resulting radiation exposure is amongst the highest in comparison with other European countries. To reduce medical radiation exposure and to safeguard radiation protection regulations, the X-ray ordinance stipulates a justification of each individual X-ray application. The justification principle means that the X-ray application should produce sufficient health benefit to offset the radiation risk. Such a benefit-risk assessment needs an adequate estimation of radiation risk. The aim of this paper is to explain the principles of benefit-risk assessment for different situations (e.g. healthcare and screening). The basics and concepts of radiation effects and radiation epidemiology as well as examples of risk estimation and benefit-risk assessments are given.

[Nuclear-medical irradiation during pregnancy. Risk assessment for the offspring]. / Nuklearmedizinische Strahlenexpositionen während der Schwangerschaft. Risikoabschätzungen für die Leibesfrucht.

UNLABELLED: AIM To estimate and evaluate the risks for the offspring due to the administration of radiopharmaceuticals to women during the first pregnancy weeks after conception (weeks p.c.). METHODS: The in-utero exposition of the embryo due to diagnostic nuclear medicine procedures, for which diagnostic reference levels (DRL) are specified, as well as due to radio iodine therapy (RIT) was determined. To this end, it is assumed that the activity of the diagnostic radiopharmaceuticals administered to the mother corresponds with the DRL and amounts to 600 MBq or 4 GBq 131I for RIT of benign or malignant thyroid disease, respectively. Based on these data, the radiation risk for the offspring was assessed and compared with the spontaneous risks (R0). RESULTS: The dose for the offspring does not exceed 7.8 mSv for the diagnostic procedures considered, resulting in an excess risk for the offspring of less than 0.12% (R0 approximately 25%) to die from cancer during life, of less than 0.07% (R0 approximately 0.2%) to develop cancer up to the age of 15 years, and of less than 0.16% (R0 approximately 2%) for hereditary effects. RIT during the first 8 weeks p.c. results in doses for the offspring of about 100-460 mSv, resulting in an excess risk for malformations of the child of 3.4%-22% (R0 approximately 6%). CONCLUSIONS: The risk of stochastic radiation effects for the offspring due to a diagnostic nuclear medicine procedure of the mother during the first 8 weeks p.c. is--compared with the spontaneous risks--very small; deterministic effects are unlikely. In contrast, deterministic effects for the offspring may occur following RIT. In order to decide on a possibly indicated abortion after RIT, an individual risk assessment is mandatory.

Paclitaxel encapsulated in cationic lipid complexes (MBT-0206) impairs functional tumor vascular properties as detected by dynamic contrast enhanced magnetic resonance imaging.

Cationic lipid complexes have been shown to be bound and internalized selectively by angiogenic tumor endothelial cells after intravenous injection. Based on this phenomenon, the chemotherapeutic agent paclitaxel was encapsulated into these lipid complexes providing a vascular targeting agent (MBT-0206). As noninvasive imaging techniques are of critical importance for optimizing antivascular cancer treatment in the clinic, we have evaluated the antivascular effects of MBT-0206 in the A-MEL-3 solid tumor model using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Twenty-four hours after three intravenous applications of MBT-0206, tumors of treated animals demonstrated a significant decrease of intratumoral blood volume and an increase of vascular permeability in comparison to size-matched control tumors. In contrast, animals treated with conventional paclitaxel given as Taxol at equal drug dose did not show any significant differences in vascular parameters acquired by DCE-MRI in comparison to controls. Immunohistological analysis confirmed a significant reduction of microvessel density in MBT-0206 treated tumors. Moreover, a significant increase of intratumoral microvascular occlusion following MBT-0206 treatment was observed compared to controls and paclitaxel treated animals. In conclusion, antivascular tumor therapy with MBT-0206 significantly impairs functional tumor microcirculation. DCE-MRI is a promising tool to quantify the antivascular effects of MBT-0206 during treatment.

[Radiation exposure of patients from diagnostic and interventional X-ray procedures. Facts, assessment and trends]. / Strahlenexposition von Patienten durch diagnostische und interventionelle Röntgenanwendungen. Fakten, Bewertung und Trends.

Man-made radiation exposure to the German population predominantly results from the medical use of ionizing radiation. According to the most recent evaluation, the mean effective dose per inhabitant and year from X-ray procedures increased from 1.6 to 1.8 mSv between 1996 and 2001. This rise is mainly caused by the expanding use of CT and reflects the growing importance of this imaging modality. Besides actual data on the frequency and dose of various types of X-ray examinations, patient-specific factors will be highlighted which have to be considered in the assessment of the associated individual and collective radiation risk. Moreover, different concepts to reduce radiation exposure of patients will be discussed as well as some current trends in health service that may affect radiation hygiene -- such as diagnosis-related groups for inpatients and CT screening.

[Introduction of a mammography screening program in Germany. Consideration of benefits and risks]. / Einführung eines Mammographiescreeningprogramms in Deutschland Erwägungen zu Nutzen und Risiko.

For women between 50 and 70 years of age, X-ray mammography presently represents the most effective method for early breast cancer detection. It is commonly accepted that quality assured mammography examinations conducted at regular intervals can reduce mortality from breast cancer. In the year 2002, the German Bundestag agreed to the implementation of a mammography screening program for Germany based on the European guidelines. The effectiveness of a mammography screening program is controversially discussed and two of the most commonly cited hazards are the occurrence of false-positive results and the so-called overdiagnosis. Another issue of criticism is the radiation risk due to the mammography examinations. However, in women aged 50-70 years the radiation risk has no substantial importance. In contrast to the present situation in Germany in which opportunistic screening is widespread, standardized quality assured screening will guarantee that false-positive rates are kept as low as possible and that further assessment diagnostics are effective and minimally invasive.

Morpho-functional visualization of dynamic MR-mammography.

In view of an increasing use of breast MRI supplementing X-ray mammography, the purpose of this study was the development of a method for fast and efficient analysis of dynamic MR image series of the female breast. The image data sets were acquired with a saturation-recovery-turbo-FLASH sequence facilitating the detection of the kinetics of the contrast agent concentration in the whole breast with a high temporal and spatial resolution. In addition, a morphological 3D-FLASH data set was acquired. The dynamic image data sets were analyzed by tracer kinetic modeling in order to describe the physiological processes underlying the contrast enhancement in mathematical terms and thus enable the estimation of functional tissue specific parameters, reflecting the status of microcirculation. To display morphological and functional tissue information simultaneously, a multidimensional real-time visualization system (using 3D-texture mapping) was developed, which enables a practical and intuitive human-computer interface in virtual reality. The spatially differentiated representation of the computed functional tissue parameters superimposed on the anatomical information offers several possibilities: improved discernibility of contrast enhancement, inspection of the data volume in 3D-space and localization of lesions in space and thus fast and more natural recognition of topological coherencies. In a feasibility study, it could be demonstrated that multidimensional visualization of contrast enhancement in virtual reality is practical. Especially, detection and localization of multiple breast lesions may be an important application

Assessment of a theoretical formalism for dose estimation in CT: an anthropomorphic phantom study.

Dose assessment in computed tomography (CT) is challenging due to the vast variety of CT scanners and imaging protocols in use. In the present study, the accurateness of a theoretical formalism implemented in the PC program CT-EXPO for dose calculation was evaluated by means of phantom measurements. Phantom measurements were performed with four 1-slice, four 4-slice and two 16-slice spiral CT scanners. Firstly, scanner-specific nCTDIw values were measured and compared with the corresponding standard values used for dose calculation. Secondly, effective doses were determined for three CT scans (head, chest and pelvis) performed at each of the ten installations from readings of thermoluminescent dosimeters distributed inside an anthropomorphic Alderson phantom and compared with the corresponding dose values computed with CT-EXPO. Differences between standard and individually measured nCTDIw values were less than 16%. Statistical analysis yielded a highly significant correlation (P < 0.001) between calculated and measured effective doses. The systematic and random uncertainty of the dose values calculated using standard nCTDIw values was about -9 and +/- 11%, respectively. The phantom measurements and model calculations were carried out for a variety of CT scanners and representative scan protocols validate the reliability of the dosimetric formalism considered-at least for patients with a standard body size and a tube voltage of 120 kV selected for the majority of CT scans performed in our study.

Morphofunctional visualization of MR-mammography in virtual reality.

In view of an increasing use of breast MRI supplementing X-ray mammography, the purpose of this study was the development of a method for fast and efficient analysis of dynamic MR image series of the female breast. The dynamic image data sets were analyzed by tracer kinetic modeling in order to describe the physiological processes underlying the contrast enhancement in mathematical terms and thus to enable the estimation of functional tissue specific parameters, reflecting the status of microcirculation. To display morphological and functional tissue information simultaneously, a multidimensional real-time visualization system (using 3D-texture mapping) was developed, which enables a practical and intuitive human-computer interface in virtual reality.

Radiation exposure in multi-slice versus single-slice spiral CT: results of a nationwide survey.

Multi-slice (MS) technology increases the efficacy of CT procedures and offers new promising applications. The expanding use of MSCT, however, may result in an increase in both frequency of procedures and levels of patient exposure. It was, therefore, the aim of this study to gain an overview of MSCT examinations conducted in Germany in 2001. All MSCT facilities were requested to provide information about 14 standard examinations with respect to scan parameters and frequency. Based on this data, dosimetric quantities were estimated using an experimentally validated formalism. Results are compared with those of a previous survey for single-slice (SS) spiral CT scanners. According to the data provided for 39 dual- and 73 quad-slice systems, the average annual number of patients examined at MSCT is markedly higher than that examined at SSCT scanners (5500 vs 3500). The average effective dose to patients was changed from 7.4 mSv at single-slice to 5.5 mSv and 8.1 mSv at dual- and quad-slice scanners, respectively. There is a considerable potential for dose reduction at quad-slice systems by an optimisation of scan protocols and better education of the personnel. To avoid an increase in the collective effective dose from CT procedures, a clear medical justification is required in each case.

[Diffusion-weighted MRI--a new parameter for advanced rectal carcinoma?]. / Diffusionsgewichtete Magnetresonanztomographie--Ein neuer Prognoseparameter beim fortgeschrittenen Rektumkarzinom?

PURPOSE: To evaluate the predictive value of apparent diffusion coefficient (ADC) on therapy outcome of combined chemoradiation in patients with primary carcinoma of the rectum. MATERIALS AND METHOD: Prior to standardized, combined, neoadjuvant chemoradiation, 16 patients with primary carcinoma of the rectum (cT3) were examined with magnetic resonance imaging (MRI). Diffusion-weighted spin echo echo-planar images (SE-EPI) and contrast-enhanced T 1 -weighted spin echo (SE) images at 1.5 Tesla were obtained. The mean ADC of the tumor region was calculated and correlated with the therapy outcome substantiated by postsurgical histopathologic staging. RESULTS: Tumor down-staging (pT0-2) occurred in 9 patients (therapy responders) and no down-staging (pT3) in 7 patients (therapy non-responders). The mean ADC measured 0.476 +/- 0.114 x 10(-3) mm 2/s in the responder group and 0.703 +/- 0.085 x 10(-3) mm 2/s in the non-responder group. Comparison of the mean ADC between the groups reached statistical significance (p = 0.001). CONCLUSION: The mean ADC might be a new quantitative parameter to predict therapy outcome of combined preoperative chemoradiation in patients with primary carcinoma of the rectum.

Dynamic MR-mammography in virtual reality.

In view of an increasing use of breast MRI supplementing X-ray mammography, the purpose of this study was the development of a method for fast and efficient analysis of dynamic MR image series of the female breast. The image data sets were acquired with a saturation-recovery-turbo-FLASH sequence facilitating the detection of the kinetics of the contrast agent concentration in the whole breast with. In addition, a morphological 3D-FLASH data set was acquired. The dynamic image data sets were analyzed by tracer kinetic modeling in order to describe the physiological processes underlying the contrast enhancement in mathematical terms and thus to enable the estimation of functional tissue specific parameters, reflecting the status of microcirculation. To display morphological and functional tissue information simultaneously, a multidimensional real-time visualization system (using 3D-texture mapping) was developed, which enables a practical and intuitive human-computer interface in virtual reality. The spatially differentiated representation of the computed functional tissue parameters superimposed on the anatomical information offers several possibilities: improved discernibility of contrast enhancement; inspection of the data volume in 3D-space using the features of rotation and transparency variation; localization of lesions in space and thus fast and more natural recognition of topological coherencies. In a feasibility study, it could be demonstrated that multidimensional visualization of contrast enhancement in virtual reality is a practicable idea. Especially, detection and localization of multiple breast lesions may be an important application.

Quantitative imaging of tumour blood flow by contrast-enhanced magnetic resonance imaging.

Tumour blood flow plays a key role in tumour growth, formation of metastasis, and detection and treatment of malignant tumours. Recent investigations provided increasing evidence that quantitative analysis of tumour blood flow is an indispensable prerequisite for developing novel treatment strategies and individualizing cancer therapy. Currently, however, methods for noninvasive, quantitative and high spatial resolution imaging of tumour blood flow are rare. We apply here a novel approach combining a recently established ultrafast MRI technique, that is T(1)-relaxation time mapping, with a tracer kinetic model. For validation of this approach, we compared the results obtained in vivo with data provided by iodoantipyrine autoradiography as a reference technique for the measurement of tumour blood flow at a high resolution in an experimental tumour model. The MRI protocol allowed quantitative mapping of tumour blood flow at spatial resolution of 250 x 250 microm(2). Correlation of data from the MRI method with the iodantipyrine autoradiography revealed Spearman's correlation coefficients of Rs = 0.851 (r = 0.775, P < 0.0001) and Rs = 0.821 (r = 0.72, P = 0.014) for local and global tumour blood flow, respectively. The presented approach enables noninvasive, repeated and quantitative assessment of microvascular perfusion at high spatial resolution encompassing the entire tumour. Knowledge about the specific vascular microenvironment of tumours will form the basis for selective antivascular cancer treatment in the future.

Tumor microcirculation evaluated by dynamic magnetic resonance imaging predicts therapy outcome for primary rectal carcinoma.

Contrast enhanced dynamic studies of malignant tumors performed by computed tomography or magnetic resonance imaging (MRI) are increasingly applied to characterize tumor microcirculation for the prediction of therapy outcome. The aim of our study was to correlate perfusion index (PI) values determined in primary rectal carcinoma before chemoradiation with therapy outcome. In 17 patients with clinically staged T3 primary rectal carcinoma, dynamic MRI was performed before the onset of therapy using an ultrafast T1-mapping sequence. On the basis of the acquired data sets, PI values were calculated on a pixel-by-pixel basis. To characterize the heterogeneity of tumor microcirculation, relative cumulative frequency histograms of PI values within the tumors were computed. Subsequent resection of the tumors allowed correlating PI with histopathological classification. In 12 of 17 patients, T-downstaging as a response to therapy was found, whereas in the remaining 5 patients no therapy response was observed after chemoradiation. A statistically significant difference between both groups was found for the mean PI (P < 0.001; 8.5+/-1.7 ml/min/100 g versus 11.4+/-0.7 ml/min/100 g). Analyzing the cumulative frequency histograms for both groups revealed an optimal discrimination for a P1 value of 12.6 ml/min/100 g. The fraction of pixels in the tumor with PI values larger than 12.6 ml/min/100 g was significantly different (P < 0.001) between therapy-responding (3+/-3.6%) and therapy-nonresponding tumors (21+/-4.3%). The results indicate either a reduced supply of nutrients as well as chemotherapeutic agents attributable to increased shunt flow or highly aggressive tumor cell clusters characterized by increased angiogenic activity. Noninvasive PI measurements by dynamic MRI in rectal carcinoma before therapy seem to be of predictive value for therapy outcome in patients scheduled for preoperative chemoradiation.

Lung volume recruitment in lambs during high-frequency oscillatory ventilation using respiratory inductive plethysmography.

Monitoring lung volume is important in the treatment of acute hypoxemic respiratory failure. However, there are no tools available for lung volume measurement to guide ventilator management during high-frequency oscillatory ventilation (HFOV) and during dynamic changes in conventional ventilation (CV). We studied the performance of a new respiratory inductive plethysmograph (RIP) with modified software. We measured Delta changes in lung volume above end-expiratory volume (V(RIP)) during HFOV and studied whether changes in V(RIP) parallel changes in mean airway pressure. Calibration of the plethysmograph was made by serial injections of a known gas volume in six term (140 d gestation) and eight preterm (125 d gestation) lambs. Linear regression analysis of the relationship between injected gas volume and V(RIP) showed strong correlation (r(2) = 0.93-1.00 term animals, r(2) = 0.86-1.00 preterm animals). The pressure volume curves from the calibration with the injected gas volumes also correlated well with the pressure volume curves extrapolated from changes in V(RIP). Lung hysteresis was clearly demonstrated with RIP after changes in mean airway pressure during HFOV and after changes in positive end-expiratory pressure during CV. We conclude that measurements of lung volume in term and preterm lambs by use of modified RIP correlate well with changes in mean airway pressure during HFOV, with static pressure volume curves and with changes in positive end-expiratory pressure during CV. We speculate that this technique may provide clinically useful information about changes in lung volume during HFOV and CV. However, evaluation of the precision and chronic stability of RIP measurements over prolonged periods will require further studies.