Lung Cancer Screening with Low-Dose CT: Radiation Risk and Benefit-Risk Assessment for Different Screening Scenarios.

Lung cancer is a severe disease that affects predominantly smokers and represents a leading cause of cancer death in Europe. Recent meta-analyses of randomized controlled trials (RCTs) have yielded that low-dose computed tomography (LDCT) screening can significantly reduce lung cancer mortality in heavy smokers or ex-smokers by about 20% compared to a control group of persons who did not receive LDCT. This benefit must be weighed against adverse health effects associated with LDCT lung screening, in particular radiation risks. For this purpose, representative organ doses were determined for a volume CT dose index of 1 mGy that can be achieved on modern devices. Using these values, radiation risks were estimated for different screening scenarios by means of sex-, organ-, and age-dependent radio-epidemiologic models. In particular, the approach was adjusted to a Western European population. For an annual LDCT screening of (ex-)smokers aged between 50 and 75 years, the estimated radiation-related lifetime attributable risk to develop cancer is below 0.25% for women and about 0.1% for men. Assuming a mortality reduction of about 20% and taking only radiation risks into account, this screening scenario results in a benefit-risk ratio of about 10 for women and about 25 for men. These benefit-risk ratio estimates are based on the results of RCTs of the highest evidence level. To ensure that the benefit outweighs the radiation risk even in standard healthcare, strict conditions and requirements must be established for the entire screening process to achieve a quality level at least as high as that of the considered RCTs.

Lung Cancer Screening with Low-Dose CT in Smokers: A Systematic Review and Meta-Analysis.

Lung cancer continues to be one of the main causes of cancer death in Europe. Low-dose computed tomography (LDCT) has shown high potential for screening of lung cancer in smokers, most recently in two European trials. The aim of this review was to assess lung cancer screening of smokers by LDCT with respect to clinical effectiveness, radiological procedures, quality of life, and changes in smoking behavior. We searched electronic databases in April 2020 for publications of randomized controlled trials (RCT) reporting on lung cancer and overall mortality, lung cancer morbidity, and harms of LDCT screening. A meta-analysis was performed to estimate effects on mortality. Forty-three publications on 10 RCTs were included. The meta-analysis of eight studies showed a statistically significant relative reduction of lung cancer mortality of 12% in the screening group (risk ratio = 0.88; 95% CI: 0.79-0.97). Between 4% and 24% of screening-LDCT scans were classified as positive, and 84-96% of them turned out to be false positive. The risk of overdiagnosis was estimated between 19% and 69% of diagnosed lung cancers. Lung cancer screening can reduce disease-specific mortality in (former) smokers when stringent requirements and quality standards for performance are met.

Early Detection of Diseases by Radiological Imaging: New Legal Situation and Evaluation of Service Offers using CT Examinations as an Example. / Früherkennung von Krankheiten mittels radiologischer Bildgebung: Neue Rechtslage und Bewertung von Leistungsangeboten am Beispiel von CT-Untersuchungen.

BACKGROUND: Radiological imaging offers promising prospects for the early detection of diseases. In Germany, the legal framework for such examinations was created by the Radiation Protection Law, which entered into force on December 31, 2018. Under this law, each specific type of radiodiagnostic screening of non-communicable diseases needs an approval on a generic level (permission) by a federal statutory ordinance, defining the specific requirements and conditions. It is the aim of the present paper, (i) to present in detail the new legal situation and (ii) to assess actual service offers for the screening of asymptomatic persons using CT examinations as an example. METHOD: In February 2019, radiology institutions in Germany illegally offering on the Internet CT examinations for the screening of lung and colon cancer or coronary artery disease were identified. For each type of examination, 50 pertinent websites were evaluated particularly regarding the general information on the offered screening examination and the concrete procedure. RESULTS: In the vast majority of cases, the information provided on the websites was inadequate and disproportionately emphasized the benefits over the risks of the screening examination. Moreover, the offers differed substantially with respect to the age and risks factors of potential participants, the frequency of examinations, the screening procedure, and the diagnostic workup. CONCLUSION: The evaluated service offers strongly substantiate the need to define requirements and conditions regarding radiological screening examinations by statutory ordinances, in order to ensure an informed decision of potential screening participants as well as the benefit versus the risks of the procedures. KEY POINTS: · High-evidence studies prove the benefit of radiological screening for some diseases.. · In Germany, screening examinations are only permissible when stated in a federal statutory ordinance.. · At present, only mammography screening for breast cancer is permitted in Germany.. · CT screening examinations currently being conducted in Germany do not fulfill the legal and professional requirements.. · A review process has been initiated regarding possible generic approval of lung cancer screening.. CITATION FORMAT: · Brix G, Nekolla EA, Griebel J. Early Detection of Diseases by Radiological Imaging: New Legal Situation and Evaluation of Service Offers using CT Examinations as an Example. Fortschr Röntgenstr 2020; 192: 139 - 148.

[Reporting and information system for significant events related to radiation exposures in medicine: Structure, responsibilities and reporting criteria]. / Melde- und Informationssystem für bedeutsame Vorkommnisse bei Strahlenanwendungen in der Medizin: Struktur, Zuständigkeiten und Meldekriterien.

The increasing frequency and complexity of medical radiation exposures to humans inevitably result in higher risks of harmful unintended or accidental radiation exposures. To ensure a high level of protection and its continuous improvement, the Directive 2013/59/Euratom thus requires to systematically record and analyze both events and near-miss events as well as, in the case of their significance, to disseminate information regarding lessons learned from these events promptly and nationwide to improve radiation protection in medicine. These requirements have been transposed into German legislation by the new radiation protection law and radiation protection ordinance that entered into force simultaneously on December 31th, 2018. The reporting and information system as provided by these regulations as well as the tasks, duties and powers of the parties involved are presented in the first part of this review article. In the second part, the established application-specified criteria for the significance - and thus the notification requirement - of (near-miss) events are itemized and explicated.

Two-compartment modeling of tissue microcirculation revisited.

PURPOSE: Conventional two-compartment modeling of tissue microcirculation is used for tracer kinetic analysis of dynamic contrast-enhanced (DCE) computed tomography or magnetic resonance imaging studies although it is well-known that the underlying assumption of an instantaneous mixing of the administered contrast agent (CA) in capillaries is far from being realistic. It was thus the aim of the present study to provide theoretical and computational evidence in favor of a conceptually alternative modeling approach that makes it possible to characterize the bias inherent to compartment modeling and, moreover, to approximately correct for it. METHODS: Starting from a two-region distributed-parameter model that accounts for spatial gradients in CA concentrations within blood-tissue exchange units, a modified lumped two-compartment exchange model was derived. It has the same analytical structure as the conventional two-compartment model, but indicates that the apparent blood flow identifiable from measured DCE data is substantially overestimated, whereas the three other model parameters (i.e., the permeability-surface area product as well as the volume fractions of the plasma and interstitial distribution space) are unbiased. Furthermore, a simple formula was derived to approximately compute a bias-corrected flow from the estimates of the apparent flow and permeability-surface area product obtained by model fitting. To evaluate the accuracy of the proposed modeling and bias correction method, representative noise-free DCE curves were analyzed. They were simulated for 36 microcirculation and four input scenarios by an axially distributed reference model. RESULTS: As analytically proven, the considered two-compartment exchange model is structurally identifiable from tissue residue data. The apparent flow values estimated for the 144 simulated tissue/input scenarios were considerably biased. After bias-correction, the deviations between estimated and actual parameter values were (11.2 ± 6.4) % (vs. (105 ± 21) % without correction) for the flow, (3.6 ± 6.1) % for the permeability-surface area product, (5.8 ± 4.9) % for the vascular volume and (2.5 ± 4.1) % for the interstitial volume; with individual deviations of more than 20% being the exception and just marginal. Increasing the duration of CA administration only had a statistically significant but opposite effect on the accuracy of the estimated flow (declined) and intravascular volume (improved). CONCLUSIONS: Physiologically well-defined tissue parameters are structurally identifiable and accurately estimable from DCE data by the conceptually modified two-compartment model in combination with the bias correction. The accuracy of the bias-corrected flow is nearly comparable to that of the three other (theoretically unbiased) model parameters. As compared to conventional two-compartment modeling, this feature constitutes a major advantage for tracer kinetic analysis of both preclinical and clinical DCE imaging studies.

Justification of CT for Individual Health Assessment of Asymptomatic Persons: A World Health Organization Consultation.

An international expert consultation was convened by the World Health Organization (WHO). The purpose of the meeting was to review the use of CT in examining asymptomatic people. This is often referred to as individual health assessment (IHA). IHA was identified as a global phenomenon unenthusiastically tolerated, and not actively promoted, structured, or regulated in most countries. This paper identifies the state of the art for IHA and some considerations in relation to its justification, in different regions of the world. The outcomes reached include the following: questions around terminology and culture of IHA practice; review of IHA in some countries, regions, and international bodies; dilemmas for participants in IHA; risk communication, education, and training for professions and public; the desirability of guidelines and clinical audit; social, ethical, public health, and resource considerations; and a framework for IHA and regulatory considerations. Three subcategories of examination for asymptomatic individuals were identified: formal screening programs; examinations for which the evidence base or risk profile is incomplete; and opportunistic examinations with little or no evidence or risk profile to suggest they have any merit. The latter challenges the justification principle of radiation protection. In addition, the issue of the costs, direct and indirect, associated with false positives and/or equivocal/incidental findings were highlighted. These and other considerations make it difficult to view some IHA as a bona fide medical activity. To allow it to be viewed as such requires that it be conducted within a robust clinical governance framework that includes regulatory dimensions.

Radiation protection issues in dynamic contrast-enhanced (perfusion) computed tomography.

Dynamic contrast-enhanced (DCE) CT studies are increasingly used in both medical care and clinical trials to improve diagnosis and therapy management of the most common life-threatening diseases: stroke, coronary artery disease and cancer. It is thus the aim of this review to briefly summarize the current knowledge on deterministic and stochastic radiation effects relevant for patient protection, to present the essential concepts for determining radiation doses and risks associated with DCE-CT studies as well as representative results, and to discuss relevant aspects to be considered in the process of justification and optimization of these studies. For three default DCE-CT protocols implemented at a latest-generation CT system for cerebral, myocardial and cancer perfusion imaging, absorbed doses were measured by thermoluminescent dosimeters at an anthropomorphic body phantom and compared with thresholds for harmful (deterministic) tissue reactions. To characterize stochastic radiation risks of patients from these studies, life-time attributable cancer risks (LAR) were estimated using sex-, age-, and organ-specific risk models based on the hypothesis of a linear non-threshold dose-response relationship. For the brain, heart and pelvic cancer studies considered, local absorbed doses in the imaging field were about 100-190 mGy (total CTDI(vol), 200 mGy), 15-30 mGy (16 mGy) and 80-270 mGy (140 mGy), respectively. According to a recent publication of the International Commission on Radiological Protection (ICRP Publication 118, 2012), harmful tissue reactions of the cerebro- and cardiovascular systems as well as of the lenses of the eye become increasingly important at radiation doses of more than 0.5 Gy. The LARs estimated for the investigated cerebral and myocardial DCE-CT scenarios are less than 0.07% for males and 0.1% for females at an age of exposure of 40 years. For the considered tumor location and protocol, the corresponding LARs are more than 6 times as high. Stochastic radiation risks decrease substantially with age and are markedly higher for females than for males. To balance the diagnostic needs and patient protection, DCE-CT studies have to be strictly justified and carefully optimized in due consideration of the various aspects discussed in some detail in this review.

On impulse response functions computed from dynamic contrast-enhanced image data by algebraic deconvolution and compartmental modeling.

Concentration-time courses measured by dynamic contrast-enhanced (DCE) imaging can be described by a convolution of the arterial input with an impulse response function, Q(T)(t), characterizing tissue microcirculation. Data analysis is based on two different approaches: computation of Q(T)(t) by algebraic deconvolution (AD) and subsequent evaluation according to the indicator dilution theory (IDT) or parameterization of Q(T)(t) by analytical expressions derived by compartmental modeling. Pitfalls of both strategies will be addressed in this study. Tissue data acquired by DCE-CT in patients with head-and-neck cancer and simulated by a reference model (MMID4) were analyzed by a two-compartment model (TCM), a permeability-limited two-compartment model (PL-TCM) and AD. Additionally, MMID4 was used to compute the 'true' response function that corresponds to the simulated tumor data. TCM and AD yielded accurate fits, whereas PL-TCM performed worse. Nevertheless, the corresponding response functions diverge markedly. The response curves obtained by TCM decrease exponentially in the early perfusion phase and overestimate the tissue perfusion, Q(T)(0). AD also resulted in response curves starting with a negative slope and not - as the 'true' response function in accordance with the IDT - with a horizontal plateau. They are thus not valid responses in the sense of the IDT that can be used unconditionally for parameter estimation. Response functions differing considerably in shape can result in virtually identical tissue curves. This non-uniqueness makes a strong argument not to use algebraic but rather analytical deconvolution to reduce the class of solutions to representatives that are in accordance with a-priori knowledge. To avoid misinterpretations and systematic errors, users must be aware of the pitfalls inherent to the different concepts.

Tracer kinetic modelling of tumour angiogenesis based on dynamic contrast-enhanced CT and MRI measurements.

PURPOSE: Technical developments in both magnetic resonance imaging (MRI) and computed tomography (CT) have helped to reduce scan times and expedited the development of dynamic contrast-enhanced (DCE) imaging techniques. Since the temporal change of the image signal following the administration of a diffusible, extracellular contrast agent (CA) is related to the local blood supply and the extravasation of the CA into the interstitial space, DCE imaging can be used to assess tissue microvasculature and microcirculation. It is the aim of this review to summarize the biophysical and tracer kinetic principles underlying this emerging imaging technique offering great potential for non-invasive characterization of tumour angiogenesis. METHODS: In the first part, the relevant contrast mechanisms are presented that form the basis to relate signal variations measured by serial CT and MRI to local tissue concentrations of the administered CA. In the second part, the concepts most widely used for tracer kinetic modelling of concentration-time courses derived from measured DCE image data sets are described in a consistent and unified manner to highlight their particular structure and assumptions as well as the relationships among them. Finally, the concepts presented are exemplified by the analysis of representative DCE data as well as discussed with respect to present and future applications in cancer diagnosis and therapy. RESULTS: Depending on the specific protocol used for the acquisition of DCE image data and the particular model applied for tracer kinetic analysis of the derived concentration-time courses, different aspects of tumour angiogenesis can be quantified in terms of well-defined physiological tissue parameters. CONCLUSIONS: DCE imaging offers promising prospects for improved tumour diagnosis, individualization of cancer treatment as well as the evaluation of novel therapeutic concepts in preclinical and early-stage clinical trials.

Estimation of tissue perfusion by dynamic contrast-enhanced imaging: simulation-based evaluation of the steepest slope method.

OBJECTIVE: Tissue perfusion is frequently determined from dynamic contrast-enhanced CT or MRI image series by means of the steepest slope method. It was thus the aim of this study to systematically evaluate the reliability of this analysis method on the basis of simulated tissue curves. METHODS: 9600 tissue curves were simulated for four noise levels, three sampling intervals and a wide range of physiological parameters using an axially distributed reference model and subsequently analysed by the steepest slope method. RESULTS: Perfusion is systematically underestimated with errors becoming larger with increasing perfusion and decreasing intravascular volume. For curves sampled after rapid contrast injection with a temporal resolution of 0.72 s, the bias was less than 23% when the mean residence time of tracer molecules in the intravascular distribution space was greater than 6 s. Increasing the sampling interval and the noise level substantially reduces the accuracy and precision of estimates, respectively. CONCLUSIONS: The steepest slope method allows absolute quantification of tissue perfusion in a computationally simple and numerically robust manner. The achievable degree of accuracy and precision is considered to be adequate for most clinical applications.

Pharmacokinetic analysis of tissue microcirculation using nested models: multimodel inference and parameter identifiability.

The purpose of this study is to evaluate the identifiability of physiological tissue parameters by pharmacokinetic modeling of concentration-time curves derived under conditions that are realistic for dynamic-contrast-enhanced (DCE) imaging and to assess the information-theoretic approach of multimodel inference using nested models. Tissue curves with a realistic noise level were simulated by means of an axially distributed multipath reference model using typical values reported in literature on plasma flow, permeability-surface area product, and volume fractions of the intravascular and interstitial space. The simulated curves were subsequently analyzed by a two-compartment model containing these physiological quantities as fit parameters as well as by two reduced models with only three and two parameters formulated for the case of a permeability-limited and a flow-limited scenario, respectively. The competing models were ranked according to Akaike's information criterion (AIC), balancing the bias versus variance trade-off. To utilize the information available from all three models, model-averaged parameters were estimated using Akaike weights that quantify the relative strength of evidence in favor of each model. As compared to the full model, the reduced models yielded equivalent or even superior AIC values for scenarios where the structural information in the tissue curves on either the plasma flow or the capillary permeability was limited. Multimodel inference took effect to a considerable extent in half of the curves and improved the precision of the estimated tissue parameters. As theoretically expected, the plasma flow was subject to a systematic (but largely correctable) overestimation, whereas the other three physiological tissue parameters could be determined in a numerically robust and almost unbiased manner. The presented concept of pharmacokinetic analysis of noisy DCE data using three nested models under an information-theoretic paradigm offers promising prospects for the noninvasive quantification of physiological tissue parameters.

Risks and safety aspects related to PET/MR examinations.

INTRODUCTION: The introduction of positron emission tomography (PET)/magnetic resonance (MR) systems into medical practice in the foreseeable future may not only lead to a gain in clinical diagnosis compared to PET/computed tomography (CT) imaging due to the superior soft-tissue contrast of the MR technology but can also substantially reduce exposure of patients to ionizing radiation. On the other hand, there are also risks and health effects associated with the use of diagnostic MR devices that have to be considered carefully. OBJECTIVES: This review article summarizes biophysical and biological aspects, which are of relevance for the assessment of health effects related to the exposure of patients to both ionizing radiation in PET and magnetic and electromagnetic fields in MR. On this basis, some considerations concerning the justification and optimization of PET/MR examinations are presented--as far as this is possible at this very early stage. DISCUSSION: Current safety standards do not take into account synergistic effects of ionizing radiation and magnetic and electromagnetic fields. In the light of the developing PET/MR technology, there is an urgent need to investigate this aspect in more detail for exposure levels that will occur at PET/MR systems.

Radiation exposures of cancer patients from medical X-rays: how relevant are they for individual patients and population exposure?

X-ray procedures have a substantial impact not only on patient care but also on man-made radiation exposure. Since a reliable risk-benefit analysis of medical X-rays can only be performed for diagnosis-related groups of patients, we determined specific exposure data for patients with the ten most common types of cancer. For all patients with the considered cancers undergoing medical X-ray procedures in a maximum-care hospital between 2000 and 2005, patient- and examination-specific data were retrieved from the hospital/radiology information system. From this data, the cumulative 5-year effective dose was estimated for each patient as well as the mean annual effective dose per patient and the mean patient observation time for each cancer site. In total, 151,439 radiographic, fluoroscopic, and CT procedures, carried out in 15,866 cancer patients (age, 62+/-13 years), were evaluated. The mean 5-year cumulative dose varied between 8.6 mSv (prostate cancer) and 68.8 mSv (pancreas cancer). Due to an increasing use of CT scans, the mean annual effective dose per patient increased from 13.6 to 18.2 mSv during the 6-year period. Combining the results obtained in this study for a particular hospital with cancer incidence data for Germany, we estimated that cancer patients having X-ray studies constitute at least 1% of the population but receive more than 10% of the total effective dose related to all medical X-ray procedures performed nationwide per year. A large fraction of this dose is radiobiologically ineffective due to the reduced life expectancy of cancer patients.

Sphere of equivalence--a novel target volume concept for intraoperative radiotherapy using low-energy X rays.

PURPOSE: Accelerated partial breast radiotherapy with low-energy photons from a miniature X-ray machine is undergoing a randomized clinical trial (Targeted Intra-operative Radiation Therapy [TARGIT]) in a selected subgroup of patients treated with breast-conserving surgery. The steep radial dose gradient implies reduced tumor cell control with increasing depth in the tumor bed. The purpose was to compare the expected risk of local recurrence in this nonuniform radiation field with that after conventional external beam radiotherapy. METHODS AND MATERIALS: The relative biologic effectiveness of low-energy photons was modeled using the linear-quadratic formalism including repair of sublethal lesions during protracted irradiation. Doses of 50-kV X-rays (Intrabeam) were converted to equivalent fractionated doses, EQD2, as function of depth in the tumor bed. The probability of local control was estimated using a logistic dose-response relationship fitted to clinical data from fractionated radiotherapy. RESULTS: The model calculations show that, for a cohort of patients, the increase in local control in the high-dose region near the applicator partly compensates the reduction of local control at greater distances. Thus a "sphere of equivalence" exists within which the risk of recurrence is equal to that after external fractionated radiotherapy. The spatial distribution of recurrences inside this sphere will be different from that after conventional radiotherapy. CONCLUSIONS: A novel target volume concept is presented here. The incidence of recurrences arising in the tumor bed around the excised tumor will test the validity of this concept and the efficacy of the treatment. Recurrences elsewhere will have implications for the rationale of TARGIT.

[Radiation risk associated with mammography screening examinations for women younger than 50 years of age]. / Strahlenrisiko infolge von Mammographie-Screening-Untersu- chungen für Frauen unter 50 Jahren.

The target group of the German mammography screening program, conducted according to the European guidelines, is clearly defined: all women aged 50 to 69 years without evidence of breast cancer are invited to screening mammography every two years. In the present study the question was raised whether breast cancer screening by means of mammography is--from the point of view of radiation hygiene--justified also for women under 50 years of age. Based on current radio-epidemiological breast cancer studies, the excess lifetime risk (ELR) to incur or die from breast cancer of a 40, 45 and 50 year old woman was assessed. Different risk models were used to estimate the radiation risk, e.g. models given for the "Life Span Study" of the atomic bomb survivors and the risk model given in the recent Biological Effects of Ionizing Radiation (BEIR) VII report. The benefit risk ratio was defined as the ratio of the number of "saved lives" due to screening to the number of deaths due to "radiation induced breast cancer". All estimations were based on the assumption that screening is taking place up to the age of 69 years, with screening examinations being performed annually up to the age of 50 and every two years from the age of 50 onwards. The glandular dose per two-view mammography investigation was assumed to be 4 mGy. The benefit due to mammography screening was assumed to be 25% for all age groups. Assuming screening from the age of 40 or 45 years, the ELR of breast cancer is on average about 3.5 or 2 times as high compared to the ELR associated with screening starting from the age of 50 years. In comparison to the benefit risk ratio, which results for women participating in a mammography screening from the age of 50 years, the benefit risk ratio for women starting with screening already from the age of 40 or 45 years is reduced by a factor of 3 or 2. With the present data--with regard to both, the benefit and the radiation risk--it appears not to be justified to expose women from the age of 40 years to the additional radiation exposure associated with a mammography screening.

Static magnetic fields induce blood flow decrease and platelet adherence in tumor microvessels.

Red blood cell flow in capillaries is reduced during exposure to strong static magnetic fields (SMFs). Intratumoral microcirculation is characterized by tortuous microvessels with chaotic architecture and by irregular, sluggish blood flow with unstable rheology. It was the aim of this study to analyze SMF exposure effects on tumor microcirculation with regard to interactions of corpuscular blood components with tumor microvessel walls. In vivo fluorescence microscopy was performed in A-Mel-3 tumors growing in dorsal skinfold chamber preparations of Syrian Golden hamsters. SMFs with varying field strength (< 600 mT) were generated by changing the distance between a strong NdFeB rod magnet and the tissue region of interest. Short-time exposure above a magnetic flux density of about 150 mT resulted in a significant reduction of red blood cell velocity (vRBC) and segmental blood flow in tumor microvessels. At the maximum strength of 587 mT, a reversible reduction of vRBC (approximately 40%) and of functional vessel densitiy (approximately 15%) was observed. Prolongation of the exposure time from 1 min to up to 3 h resulted in comparable reductions. Microvessel diameters and leukocyte-endothelial cell interactions remained unaffected by SMF exposure. However, in contrast to tumor-free striated muscle controls, exposure at the maximum flux density induced a significant increase in platelet-endothelial cell adherence in a time-dependent manner that was reversible after reducing SMF strength. These reversible changes may have implications for functional measurements of tumor microcirculation by MRI and new therapeutic strategies using strong SMFs.

Static magnetic fields affect capillary flow of red blood cells in striated skin muscle.

Blood flowing in microvessels is one possible site of action of static magnetic fields (SMFs). We evaluated SMF effects on capillary flow of red blood cells (RBCs) in unanesthetized hamsters, using a skinfold chamber technique for intravital fluorescence microscopy. By this approach, capillary RBC velocities (v(RBC)), capillary diameters (D), arteriolar diameters (D(art)), and functional vessel densities (FVD) were measured in striated skin muscle at different magnetic flux densities. Exposure above a threshold level of about 500 mT resulted in a significant (P < 0.001) reduction of v(RBC) in capillaries as compared to the baseline value. At the maximum field strength of 587 mT, v(RBC) was reduced by more than 40%. Flow reduction was reversible when the field strength was decreased below the threshold level. In contrast, mean values determined at different exposure levels for the parameters D, D(art), and FVD did not vary by more than 5%. Blood flow through capillary networks is affected by strong SMFs directed perpendicular to the vessels. Since the influence of SMFs on blood flow in microvessels directed parallel to the field as well as on collateral blood supply could not be studied, our findings should be carefully interpreted with respect to the setting of safety guidelines.

Tracer kinetic analysis of signal time series from dynamic contrast-enhanced MR imaging.

Rapid magnetic resonance imaging (MRI) makes it possible to detect the fast kinetics of tissue response after intravenous administration of a paramagnetic contrast medium (CM), reflecting the status of tissue microcirculation. In this paper, the basic physical and tracer kinetic principles of dynamic relaxivity and susceptibility contrast-enhanced MRI are reviewed. Quantitative analysis of data acquired is broken up into an MR-specific part, in which the signal variation observed is related to the CM concentration in the tissue, and an MR-independent part, in which the computed concentration time series are analyzed by tracer kinetic modeling to estimate well-defined physiological tissue parameters. The clinical application of dynamic MRI techniques is demonstrated by two representative studies.

Classification of signal-time curves obtained by dynamic magnetic resonance mammography: statistical comparison of quantitative methods.

OBJECTIVE: This study compares the performance of quantitative methods for the characterization of signal-time curves acquired by dynamic contrast-enhanced magnetic resonance mammography from 253 females. MATERIALS AND METHODS: Signal-time curves obtained from 105 parenchyma, 162 malignant, and 91 benign tissue regions were examined (243 lesions were histopathologically validated). A neural network, a nearest-neighbor, and a threshold classifier were applied to either the entire signal-time curve or pharmacokinetic and descriptive parameters calculated from the curves to differentiate between 2 (malignant or benign) or 3 tissue classes (malignant, benign, or parenchyma). The classifiers were tuned and evaluated according to their performance on 2 distinct subsets of the curves. RESULTS: The accuracy determined for the neural network and the nearest-neighbor classifiers was nearly identical (approximately 80% in case of 3 tissue classes, and approximately 76% in case of the 2 classes). In contrast, the accuracy of the threshold classifier applied to the discrimination of 3 classes was low (65%). CONCLUSION: Quantitative classifiers can support the radiologist in the diagnosis of breast lesions.

Microcirculation and microvasculature in breast tumors: pharmacokinetic analysis of dynamic MR image series.

The purpose of this study was to quantify microcirculation and microvasculature in breast lesions by pharmacokinetic analysis of Gd-DTPA-enhanced MRI series. Strongly T1-weighted MR images were acquired in 18 patients with breast lesions using a saturation-recovery-TurboFLASH sequence. Concentration-time courses were determined for blood, pectoral muscle, and breast masses and subsequently analyzed by a two-compartment model to estimate plasma flow and the capillary transfer coefficient per unit of plasma volume (F/VP, KPS/VP) as well as fractional volumes of the plasma and interstitial space (fP, fI). Tissue parameters determined for pectoral muscle (fP = 0.04 +/- 0.01, fI = 0.09 +/- 0.01, F/VP = 2.4 +/- 1.3 min(-1), and KPS/VP = 1.2 +/- 0.5 min(-1)) and 10 histologically proven carcinomas (fP = 0.20 +/- 0.07, fI = 0.34 +/- 0.16, F/VP = 2.4 +/- 0.7 min(-1), and KPS/VP = 0.86 +/- 0.62 min(-1)) agreed reasonable well with literature data. Best separation between malignant and benign lesions was obtained by the ratio KPS/F (0.35 +/- 0.17 vs. 1.23 +/- 0.65). The functional imaging technique presented appears promising to quantitatively characterize tumor pathophysiology. Its impact on diagnosis and therapy management of breast tumors, however, has to be evaluated in larger patient studies.