[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.

[Magnetic resonance imaging : Recent studies on biological effects of static magnetic and high­frequency electromagnetic fields]. / Magnetresonanztomographie : Neuere Studien zur biologischen Wirkung statischer Magnetfelder und hochfrequenter elektromagnetischer Felder.

PROBLEM: During the last few years, new studies on biological effects of strong static magnetic fields and on thermal effects of high-frequency electromagnetic fields used in magnetic resonance imaging (MRI) were published. Many of these studies have not yet been included in the current safety recommendations. METHOD: Scientific publications since 2010 on biological effects of static and electromagnetic fields in MRI were researched and evaluated. RESULTS: New studies confirm older publications that have already described effects of static magnetic fields on sensory organs and the central nervous system, accompanied by sensory perceptions. A new result is the direct effect of Lorentz forces on ionic currents in the semicircular canals of the vestibular system. Recent studies of thermal effects of high-frequency electromagnetic fields were focused on the development of anatomically realistic body models and a more precise simulation of exposure scenarios. RECOMMENDATION FOR PRACTICE: Strong static magnetic fields can cause unpleasant sensations, in particular, vertigo. In addition, they can influence the performance of the medical staff and thus potentially endanger the patient's safety. As a precaution, medical personnel should move slowly within the field gradient. High-frequency electromagnetic fields lead to an increase in the temperature of patients' tissues and organs. This should be considered especially in patients with restricted thermoregulation and in pregnant women and neonates; in these cases exposure should be kept as low as possible.

[Radiation protection in medical research : Licensing requirement for the use of radiation and advice for the application procedure]. / Strahlenschutz in der medizinischen Forschung : Genehmigungsbedürftigkeit von Strahlenanwendungen und Hinweise zum Antragsverfahren.

BACKGROUND: In Germany, persons who are to be exposed to radiation for medical research purposes are protected by a licensing requirement. However, there are considerable uncertainties on the part of the applicants as to whether licensing by the competent Federal Office for Radiation Protection is necessary, and regarding the choice of application procedure. AIM: The article provides explanatory notes and practical assistance for applicants and an outlook on the forthcoming new regulations concerning the law on radiation protection of persons in the field of medical research. MATERIALS AND METHODS: Questions and typical mistakes in the application process were identified and evaluated. RESULTS AND DISCUSSION: The qualified physicians involved in a study are responsible for deciding whether a license is required for the intended application of radiation. The decision can be guided by answering the key question whether the study participants would undergo the same exposures regarding type and extent if they had not taken part in the study. When physicians are still unsure about their decision, they can seek the advisory service provided by the professional medical societies. Certain groups of people are particularly protected through the prohibition or restriction of radiation exposure. A simplified licensing procedure is used for a proportion of diagnostic procedures involving radiation when all related requirements are met; otherwise, the regular licensing procedure should be used. The new radiation protection law, which will enter into force on the 31st of december 2018, provides a notification procedure in addition to deadlines for both the notification and the licensing procedures. In the article, the authors consider how eligible studies involving applications of radiation that are legally not admissible at present may be feasible in the future, while still ensuring a high protection level for study participants.

[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.

Quantification of pulmonary microcirculation by dynamic contrast-enhanced magnetic resonance imaging: comparison of four regularization methods.

Tissue microcirculation can be quantified by a deconvolution analysis of concentration-time curves measured by dynamic contrast-enhanced magnetic resonance imaging. However, deconvolution is an ill-posed problem, which requires regularization of the solutions. In this work, four algebraic deconvolution/regularization methods were evaluated: truncated singular value decomposition and generalized Tikhonov regularization (GTR) in combination with the L-curve criterion, a modified LCC (GTR-MLCC), and a response function model that takes a-priori knowledge into account. To this end, dynamic contrast-enhanced magnetic resonance imaging data sets were simulated by an established physiologically reference model for different signal-to-noise ratios and measured on a 1.5-T system in the lung of 10 healthy volunteers and 20 patients. Analysis of both the simulated and measured dynamic contrast-enhanced magnetic resonance imaging datasets revealed that GTR in combination with the L-curve criterion does not yield reliable and clinically useful results. The three other deconvolution/regularization algorithms resulted in almost identical microcirculatory parameter estimates for signal-to-noise ratios > 10. At low signal-to-noise ratios levels (<10) typically occurring in pathological lung regions, GTR in combination with a modified L-curve criterion approximates the true response function much more accurately than truncated singular value decomposition and GTR in combination with response function model with a difference in accuracy of up to 76%. In conclusion, GTR in combination with a modified L-curve criterion is recommended for the deconvolution of dynamic contrast-enhanced magnetic resonance imaging curves measured in the lung parenchyma of patients with highly heterogeneous signal-to-noise ratios.

[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.

[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.

[Radiation hygiene in medical X-ray imaging, part 1: physical and technical basics]. / Strahlenhygiene in der medizinischen Röntgenbildgebung, Teil 1 : Physikalisch-technische Grundlagen.

In this first part of a series of three articles on radiation hygiene in medical X-ray imaging the characteristics of X-rays, their interactions with matter and the components of X-ray equipment are described from a radiation protection point of view. The fundamental radiation protection measures like filtration and beam limitation are introduced as well as the various conventional and digital image receptor systems. Moreover the absorbed dose and other practical dose terms as well as metrological and theoretical methods for dose assessment are introduced. The aim of this paper is to explain the essential physical and technical basics of X-ray imaging and the assessment of the resulting radiation dose.

[Radiation hygiene in medical X-ray imaging: part 2: Assessment of radiation exposure and radiation protection measures]. / Strahlenhygiene in der medizinischen Röntgenbildgebung: Teil 2: Expositionsbestimmung und Strahlenschutzmaßnahmen.

In order to secure and continually improve radiation protection standards in the field of medical X-ray imaging, the German X-Ray Ordinance requires that each individual examination be properly justified and that any procedure undertaken be optimized. Diagnostic reference levels have been introduced in Germany as a measure of optimization for common and/or high-dose X-ray procedures, and are regularly checked for compliance by the competent Medical Experts Office. A prerequisite for the implementation of these regulatory requirements is the determination of readily measurable dose quantities. They also form the basis for the estimation of organ doses and of the effective dose for exposure and risk assessment. The aim of this paper is to describe the essential dosimetric concepts and methods used for the assessment of radiographic, fluoroscopic, and CT procedures. In addition, practical measures for reducing the radiation exposure of patients and personnel will be discussed.

[Diagnostic reference levels for X-ray examinations: update 2010]. / Diagnostische Referenzwerte für Röntgenuntersuchungen: Aktualisierung 2010.

The diagnostic reference levels (DRLs) for diagnostic and interventional X-ray procedures established in 2003 were updated in July 2010 by the German Federal Office for Radiation Protection on the basis of mean patient doses in X-ray facilities surveyed by the so-called competent medical expert offices. The new DRLs are immediately in force and in most cases markedly below the respective old levels. Moreover DRLs for pediatric CT examinations have been newly introduced. This article briefly summarizes the concept of DRLs and the essential changes.

Dose reduction by automatic exposure control in multidetector computed tomography: comparison between measurement and calculation.

The aim of this study was to investigate the potential of dose reduction in multidetector computed tomography (MDCT) by current-modulated automatic exposure control (AEC) and to test the reliability of the dose estimation by the conventional CT dosimetry program CT-EXPO, when an average tube current is used. Phantom measurements were performed at a CT system with 64 detector rows for four representative examination protocols, each without and with current-modulated AEC. Organ and effective doses were measured by thermoluminescence dosimeters (TLD) at an anthropomorphic Alderson phantom and compared with those given by the calculation with CT-EXPO. The application of AEC yielded dose reductions between 27 and 40% (TLD measurements). While good linearity was observed between measured and computed effective dose values both without and with AEC, the organ doses showed large deviations between measurement and calculation. The dose to patients undergoing a MDCT examination can be reduced considerably by applying a current-modulated AEC. Dosimetric algorithms using a constant current-time product provide reliable estimates of the effective dose.

[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.

Diagnostic nuclear medicine procedures in Germany between 1996 and 2002: application frequencies and collective effective doses.

AIM: Man-made radiation exposure to the German population predominantly results from the medical use of ionizing radiation. It was therefore the aim of the present study, to provide public health information concerning diagnostic nuclear medicine procedures carried out in Germany between 1996 and 2002. MATERIAL AND METHODS: Application frequencies for 10 groups of procedures were estimated from official reimbursement data provided by the German health insurance companies. Mean effective doses for these examinations were estimated from data provided by 14 clinics and 10 practices concerning the radiopharmaceuticals in use and the activities administered. RESULTS: During the period 1996-2002, a total of (3.83 +/- 0.31) million nuclear medicine procedures were performed in average per year, which corresponds to a mean annual application frequency of approximately 47 examinations per 1 000 inhabitants. More than 90% of the examinations were scintigraphies of the thyroid (37%), skeleton (25%), myocardium (13%), lungs (8%) and kidneys (8%). The averaged collective effective dose was (10.2 +/- 1.4) . 10(3) mSv per year, which corresponds to a mean annual per caput effective dose of about (0.12 +/- 0.02) mSv. Three types of procedures were responsible for about 80% of the total collective effective dose: scintigraphies of the myocardium (36%), skeleton (33%) and thyroid (10%). Averaged over all procedures carried-out, the mean effective dose per examination was (2.7 +/- 0.8) mSv. CONCLUSION: The average effective dose per inhabitant and year caused by nuclear medicine examinations is markedly lower than that resulting from medical X-ray procedures (0.12 vs. 1.8 mSv). Reduction of patient exposure may be achieved, for example, by replacing (201)Tl-labeled radiopharmaceuticals by (99m)Tc-labeled compounds.

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.

Pharmacokinetic analysis of 5-[18F]fluorouracil tissue concentrations measured with positron emission tomography in patients with liver metastases from colorectal adenocarcinoma.

The purpose of our study was to develop a pharmacokinetic model to quantify the intracellular 5-fluorouracil (5-FU) concentration in liver metastases, which is expected to be closely correlated to therapy response. In addition, the influence of the biomodulator folinic acid on the action of 5-FU in the metastases was investigated. After i.v. application of 5-FU labeled with the positron emitter fluorine-18 (5-[18F]FU), the kinetics of the regional 5-[18F]FU/uptake was measured dynamically with positron emission tomography over 120 min in 14 patients with a total of 27 liver metastases from colorectal adenocarcinoma. Activity-time curves were evaluated in the metastases, the normal liver tissue, as well as in the aorta and analyzed by a six-compartment model. The catabolic breakdown of 5-FU to alpha-fluoro-beta-alanine (FBAL) in the normal liver tissue was modeled to separate the catabolites from the cytostatic agent 5-[18F]FU and the active 5-[18F]fluorodeoxyuridine nucleotides. With our model, all measured activity-time courses could be described adequately with only small interindividual variations in parameters connected with liver and blood. Extrahepatic clearance of 5-FU was estimated as 0.66 +/- 0.33 liters/min, whereas the hepatic clearance was 0.52 +/- 0.25 liters/min. The Michaelis-Menten parameters describing the nonlinear conversion of 5-FU to FBAL were Km = 11.3 +/- 6.4 micromol and Vmax = 147.1 +/- 130.7 micromol/min. The maximum FBAL concentration in the liver was reached between 35 and 65 min after i.v. 5-FU infusion. The most sensitive parameters for therapy monitoring were k(in) and k(out), which characterize the transport in and out of the intracellular volume of the metastases, respectively. Tumor response can only be expected if k(in) is high and k(out) is low ("trapping"). These criteria were met by 6 of the 27 metastases, which were identical to those with high values for the area under the intracellular 5-FU concentration curve (AUC[meta,IC]5-FU). The parameters k(in) and k(out) were also used to investigate the influence of the biomodulating agent folinic acid on drug effect. Five of the six metastases that showed trapping belonged to patients who received folinic acid. With the exception of one patient, however, all patients who received folinic acid had multiple metastases, of which only one was able to trap 5-FU. Because patient response can only be expected when all metastases trap 5-FU, folinic acid showed no effect on the overall clinical response. With the quantitative modeling approach used, trapping of 5-FU can be assessed noninvasively and on an individual basis. This makes it possible to adjust the dose for each individual patient to optimize the treatment schedule.

Uterine cervical carcinoma: comparison of standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival.

Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as for therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this study to: (a) examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis [microvessel density (MVD) and vascular endothelial growth factor (VEGF)]; and (b) determine the ultimate value of a histomorphological and a dynamic MRI approach by the correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) and standard parameters [the maximum signal intensity increase over baseline (SI-I) and the steepest signal intensity-upslope per second (SI-U/s)] were calculated from a contrast-enhanced dynamic MRI series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD and VEGF) were compared to MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found between MVD and A (P < 0.01) and SI-I (P < 0.05). No significant relationships were observed between VEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based on k21 and SI-U/s showed that tumors with high k21 and SI-U/s values had a significantly (P < 0.05 and 0.001, respectively) worse disease outcome than did tumors with low k21 and SI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD and VEGF) had any significant power to predict patient survival. It is concluded that in patients with uterine cervical cancer: (a) the pathophysiological basis for differences in dynamic MRI is MVD but not VEGF expression; (b) a functional, dynamic MRI approach (both standard and pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than are the current histomorphological-based markers of tumor angiogenesis; and (c) compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assess MVD or patient survival.

Angiogenesis of uterine cervical carcinoma: characterization by pharmacokinetic magnetic resonance parameters and histological microvessel density with correlation to lymphatic involvement.

Dynamic studies of Gd-based contrast agents in magnetic resonance imaging (MRI) are increasingly being used for tumor characterization as well as therapy response monitoring. Because detailed knowledge regarding the pathophysiological properties, which in turn are responsible for differences in contrast enhancement, remains fairly undetermined, it was the aim of this project to: (a) examine the relationship between contrast-enhanced dynamic MRI-derived characteristics and histological microvessel density counts, a recognized surrogate of tumor angiogenesis, from primary or recurrent cancers of the uterine cervix; and (b) correlate these parameters with lymphatic involvement to characterize tumor aggressiveness in terms of lymphatic spread. Pharmacokinetic parameters (amplitude, A; exchange rate constant, k21) were calculated from a contrast-enhanced dynamic MRI series in 55 patients (ages 25-72 years; mean, 50 years) with biopsy-proven primary (n = 42) or recurrent (n = 13) uterine cervical cancer. Both pharmacokinetic parameters were correlated to histologically determined microvessel density counts (factor VIII-related antigen) and other pathological tumor characteristics obtained from the operative specimens after radical surgery. In addition, the magnetic resonance and histological data were correlated to the presence or absence of lymphatic system involvement. Pharmacokinetic MRI-derived parameters (A and k21) increased with increasing histological microvessel density counts with r = 0.41 and 0.50, respectively. Lymphatic involvement was more comprehensibly assessed by the pharmacokinetic parameter k21 compared with histological microvessel density, resulting in a higher sensitivity, overall accuracy, and comparable specificity. Contrast-enhanced MRI parameters might prove to be applicable for estimation of tumor angiogenesis in uterine cervical cancer; thus, MRI may become an additional tool to characterize malignant progression in terms of lymphatic involvement in uterine cervical cancer.

An optimized workflow for the integration of biological information into radiotherapy planning: experiences with T1w DCE-MRI.

Planning of radiotherapy is often difficult due to restrictions on morphological images. New imaging techniques enable the integration of biological information into treatment planning and help to improve the detection of vital and aggressive tumour areas. This might improve clinical outcome. However, nowadays morphological data sets are still the gold standard in the planning of radiotherapy. In this paper, we introduce an in-house software platform enabling us to combine images from different imaging modalities yielding biological and morphological information in a workflow driven approach. This is demonstrated for the combination of morphological CT, MRI, functional DCE-MRI and PET data. Data of patients with a tumour of the prostate and with a meningioma were examined with DCE-MRI by applying pharmacokinetic two-compartment models for post-processing. The results were compared with the clinical plans for radiation therapy. Generated parameter maps give additional information about tumour spread, which can be incorporated in the definition of safety margins.

PET/CT: dose-escalated image fusion?

Clinical studies demonstrate a gain in diagnostic accuracy by employing combined PET/CT instead of separate CT and PET imaging. However, whole-body PET/CT examinations result in a comparatively high radiation burden to patients and thus require a proper justification and optimization to avoid repeated exposure or over-exposure of patients. This review article summarizes relevant data concerning radiation exposure of patients resulting from the different components of a combined PET/CT examination and presents different imaging strategies that can help to balance the diagnostic needs and the radiation protection requirements. In addition various dose reduction measures are discussed, some of which can be adopted from CT practice, while others mandate modifications to the existing hard- and software of PET/CT systems.