Gunnar Brix

Publications of Gunnar Brix

• Functional computed tomography imaging.

  Authors: Christian Fink, Gunnar Brix, Sandra Simon Halliburton, Sebastian Schindera, Vicky Goh

  Investigative radiology. 01/2012; 47(1):1.

• Radiation dose at coronary CT angiography: second-generation dual-source CT versus single-source 64-MDCT and first-generation dual-source CT.

  Authors: Christian Fink, Radko Krissak, Thomas Henzler, Ursula Lechel, Gunnar Brix, Richard A P Takx, John W Nance, Joseph A Abro, Stefan O Schoenberg, U Joseph Schoepf

  AJR. American journal of roentgenology. 05/2011; 196(5):W550-7.

  The purpose of this study was to assess the radiation doses of different coronary CTA (CTA) protocols: second-generation dual-source 128-MDCT, first-generation dual-source 64-MDCT, and single-sourceThe purpose of this study was to assess the radiation doses of different coronary CTA (CTA) protocols: second-generation dual-source 128-MDCT, first-generation dual-source 64-MDCT, and single-source 64-MDCT. Thermoluminescent dosimetry was used to determine scanner-specific dose coefficients for standard coronary CTA of an anthropomorphic phantom. These coefficients were used to estimate the effective doses (EDs) of retrospectively gated, prospectively triggered, and prospectively triggered high pitch coronary CTA performed at 100 and 120 kV. The coronary CTA protocols used in imaging of 43 patients undergoing dual-source 128-MDCT were analyzed for ED, image quality, and signal-to-noise ratio. Regardless of coronary CTA protocol and CT system, imaging at 100 kV lowered the ED 40-50%. In retrospectively gated 120-kV coronary CTA, the ED ranged from 5.7 to 10.7 mSv and was approximately 50% lower with single-source 64-MDCT than with either DSCT protocol. In prospectively triggered 120-kV coronary CTA, the ED ranged from 3.8 to 4.0 mSv. The lowest ED of all protocols (1.3 mSv) was observed in prospectively triggered high-pitch 100-kV coronary CTA performed with dual-source 128-MDCT. Patient measurements showed similar dose reductions for prospective triggering and low voltage settings without an influence on signal-to-noise ratio or image quality. A combination of prospective triggering with low voltage settings is an effective measure for reducing the ED of coronary CTA to values of 2-4 mSv independent of scanner system. Further dose reduction to nearly 1 mSv can be achieved with high-pitch prospectively triggered coronary CTA.

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

  Authors: Gunnar Brix, Mona Salehi Ravesh, Stefan Zwick, Jürgen Griebel, Stefan Delorme

  Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB). 04/2011;

  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), characterizingConcentration-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.

• Phenotyping of tumor biology in patients by multimodality multiparametric imaging: relationship of microcirculation, alphavbeta3 expression, and glucose metabolism.

  Authors: Stephan Metz, Carl Ganter, Sylvie Lorenzen, Sandra van Marwick, Ken Herrmann, Florian Lordick, Stephan G Nekolla, Ernst J Rummeny, Hans-Jürgen Wester, Gunnar Brix, Markus Schwaiger, Ambros J Beer

  Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 10/2010; 51(11):1691-8.

  Both dynamic contrast-enhanced (DCE) MRI and PET provide quantitative information on tumor biology in living organisms. However, imaging biomarkers often neglect tissue heterogeneity by focusing onBoth dynamic contrast-enhanced (DCE) MRI and PET provide quantitative information on tumor biology in living organisms. However, imaging biomarkers often neglect tissue heterogeneity by focusing on distributional summary statistics. We analyzed the spatial relationship of α(v)β(3) expression, glucose metabolism, and perfusion by PET and DCE MRI, focusing on tumor heterogeneity. Thirteen patients with primary or metastasized cancer (non-small cell lung cancer, n = 9; others, n = 4) were examined with DCE MRI and with PET using (18)F-galacto-RGD and (18)F-FDG. Twenty-three different regions of interest were defined by cluster analysis based on the heterogeneity of tracer uptake. In these regions, the initial area under the gadopentetate dimeglumine concentration-time curve (IAUGC), as well as the regional blood volume (rBV) and regional blood flow (rBF), were estimated from DCE MRI and correlated with standardized uptake values from PET. Regions with simultaneously high uptake of (18)F-galacto-RGD and (18)F-FDG showed higher functional MRI data (IAUGC, 0.35 ± 0.04 mM·s; rBF, 70.2 ± 12.7 mL/min/100 g; rBV, 23.3 ± 2.7 mL/100 g) than did areas with low uptake of both tracers (IAUGC, 0.15 ± 0.04 mM·s [P < 0.01]; rBF, 28.3 ± 10.8 mL/min/100 g; rBV, 9.9 ± 1.9 mL/100 g [P < 0.01]). There was a weak to moderate correlation between the functional MRI parameters and (18)F-galacto-RGD (r = 0.30-0.62) and also (18)F-FDG (r = 0.44-0.52); these correlations were significant (P < 0.05), except for (18)F-galacto-RGD versus rBF (P = 0.17). These data show that multiparametric assessment of tumor heterogeneity is feasible by combining PET and MRI. Perfusion is highest in tumor areas with simultaneously high α(v)β(3) expression and high glucose metabolism and restricted in areas with both low α(v)β(3) expression and low glucose metabolism. The current limitations resulting from imaging with separate scanners might be overcome by future hybrid PET/MRI scanners.

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

  Authors: Gunnar Brix, Stefan Zwick, Jürgen Griebel, Christian Fink, Fabian Kiessling

  European radiology. 09/2010; 20(9):2166-75.

  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 theTissue 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. 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. 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. 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.

• Dynamic contrast-enhanced CT studies: balancing patient exposure and image noise.

  Authors: Gunnar Brix, Ursula Lechel, Markus Petersheim, Radko Krissak, Christian Fink

  Investigative radiology. 09/2010; 46(1):64-70.

  To establish the essential basis for balancing the dose versus noise trade-off in dynamic contrast-enhanced (DCE) CT by means of a phantom study. Measurements were performed at a 64-sectionTo establish the essential basis for balancing the dose versus noise trade-off in dynamic contrast-enhanced (DCE) CT by means of a phantom study. Measurements were performed at a 64-section dual-source system, using the default protocols for DCE imaging (40 scans) of the trunk (current-time product per scan, 100 mAs; voltage, 120 kVp; pixel size, 0.9 × 0.9 × 8 mm3; CTDIvol per examination, 264 mGy) and head (270 mAs, 80 kVp, 0.45 × 0.45 × 8 mm3, 429 mGy). For 3 representative sections of an anthropomorphic phantom (head, upper abdomen, pelvis) transaxial dose distributions were measured by thermoluminescent dosimeters. The image noise was determined for 5 values of the current-time product (but otherwise identical parameter settings) and 4 pixel resolutions at a water-filled trunk and head phantom. Highest exposures occurred at the periphery of the trunk and head with maximum skin entrance doses of about 300 mGy. Effective doses related to the 3 exposure scenarios were between 4 and 20 mSv, but were not at all predictive of local exposure levels. The image noise was inversely proportional to the square root of the current-time product and, with restrictions, to the pixel size. Noise levels determined for the standard settings were 13.8 HU (trunk) and 4.4 HU (head) and thus comparable with the contrast enhancement typically detected in tumors and ischemic brain tissues, respectively. The opposing requirements of risk and noise limitation in DCE-CT cannot be balanced without substantially reducing the spatial resolution. But even so, local radiation exposures are rather high for a diagnostic procedure. Indications to perform a DCE examination should thus be strictly limited to patients who really benefit from it.

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

  Authors: Gunnar Brix, Jürgen Griebel, Fabian Kiessling, Frederik Wenz

  European journal of nuclear medicine and molecular imaging. 08/2010; 37 Suppl 1:S30-51.

  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) imagingTechnical 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. 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. 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. 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.

• Simulation-based comparison of two approaches frequently used for dynamic contrast-enhanced MRI.

  Authors: Stefan Zwick, Gunnar Brix, Paul Tofts, Ralph Strecker, Annette Kopp-Schneider, Hendrik Laue, Wolfhard Semmler, Fabian Kiessling

  European radiology. 10/2009;

  PURPOSE: The purpose was to compare two approaches for the acquisition and analysis of dynamic-contrast-enhanced MRI data with respect to differences in the modelling of the arterial input-functionPURPOSE: The purpose was to compare two approaches for the acquisition and analysis of dynamic-contrast-enhanced MRI data with respect to differences in the modelling of the arterial input-function (AIF), the dependency of the model parameters on physiological parameters and their numerical stability. Eight hundred tissue concentration curves were simulated for different combinations of perfusion, permeability, interstitial volume and plasma volume based on two measured AIFs and analysed according to the two commonly used approaches. The transfer constants (Approach 1) K (trans) and (Approach 2) k (ep) were correlated with all tissue parameters. K (trans) showed a stronger dependency on perfusion, and k (ep) on permeability. The volume parameters (Approach 1) v (e) and (Approach 2) A were mainly influenced by the interstitial and plasma volume. Both approaches allow only rough characterisation of tissue microcirculation and microvasculature. Approach 2 seems to be somewhat more robust than 1, mainly due to the different methods of CA administration.

• Static magnetic fields impair angiogenesis and growth of solid tumors in vivo.

  Authors: Donata Strelczyk, Martin Eichhorn, Siiri Luedemann, Gunnar Brix, Marc Dellian, Alexander Berghaus, Sebastian Strieth

  Cancer biology & therapy. 10/2009; 8(18).

  Exposure to static magnetic fields (SMFs) results in a reduced blood flow in tumor vessels as well as in activation and adherence of platelets. Whether this phenomenon may have a significantExposure to static magnetic fields (SMFs) results in a reduced blood flow in tumor vessels as well as in activation and adherence of platelets. Whether this phenomenon may have a significant functional impact on tumors has not been investigated as yet. The aim of our study was to evaluate the effects of prolonged exposure to SMFs on tumor angiogenesis and growth. Experiments were performed in dorsal skinfold chamber preparations of Syrian Golden hamsters bearing syngenic A-Mel-3 melanomas. On three days following tumor cell implantation one group of animals was immobilized and exposed to a SMF of 586 mT for three hours. Control animals were immobilized for the same duration without SMF exposure. Using in vivo-fluorescence microscopy the field effects on tumor angiogenesis and microcirculation were analyzed for seven days. Tumor growth was assessed by repeated planimetry of the tumor area during the observation period. Exposure to SMFs resulted in a significant retardation of tumor growth ( approximately 30%). Furthermore, histological analysis showed an increased peri- and intratumoral edema in tumors exposed to SMFs. Analysis of microcirculatory parameters revealed a significant reduction of functional vessel density, vessel diameters and red blood cell velocity in tumors after exposure to SMFs compared to control tumors. These changes reflect retarded vessel maturation by antiangiogenesis. The increased edema after SMF exposure indicates an increased tumor microvessel leakiness possibly enhancing drug-uptake. Hence, SMF therapy appears as a promising new anticancer strategy-as an inhibitor of tumor growth and angiogenesis and as a potential sensitizer to chemotherapy.

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

  Authors: Gunnar Brix, Stefan Zwick, Fabian Kiessling, Jürgen Griebel

  Medical physics. 08/2009; 36(7):2923-33.

  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 realisticThe 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.

  Authors: Gunnar Brix, Elke Nekolla, Dietmar Nosske, Jürgen Griebel

  European journal of nuclear medicine and molecular imaging. 01/2009;

  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 diagnosisINTRODUCTION: 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?

  Authors: Gunnar Brix, Sven Nissen-Meyer, Ursula Lechel, Johannes Nissen-Meyer, Jürgen Griebel, Elke A Nekolla, Christoph Becker, Maximilian Reiser

  European journal of radiology. 09/2008;

  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 forX-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 8.6mSv (prostate cancer) and 68.8mSv (pancreas cancer). Due to an increasing use of CT scans, the mean annual effective dose per patient increased from 13.6 to 18.2mSv 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.

• Static Magnetic Fields Induce Blood Flow Decrease and Platelet Adherence in Tumor Microvessels.

  Authors: Sebastian Strieth, Donata Strelczyk, Martin Eichhorn, Marc Dellian, Siiri Luedemann, Jürgen Griebel, Matthias Bellemann, Alexander Berghaus, Gunnar Brix

  Cancer biology & therapy. 03/2008; 7(6).

  Red blood cell flow in capillaries is reduced during exposure to strong static magnetic fields (SMFs). Intratumoral microcirculation is characterized by tortuous microvessels with chaoticRed 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 (V(RBC)) and segmental blood flow in tumor microvessels. At the maximum strength of 587 mT, a reversible reduction of V(RBC) ( 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 plateletendothelial 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.

• [Radiation risk associated with mammography screening examinations for women younger than 50 years of age]

  Authors: Elke A Nekolla, Jürgen Griebel, Gunnar Brix

  Zeitschrift für medizinische Physik. 02/2008; 18(3):170-9.

  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 areThe 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 affect capillary flow of red blood cells in striated skin muscle.

  Authors: Gunnar Brix, Sebastian Strieth, Donata Strelczyk, Marc Dellian, Jürgen Griebel, Martin E Eichhorn, Wilfried Andrā, Matthias E Bellemann

  Microcirculation (New York, N.Y. : 1994). 01/2008; 15(1):15-26.

  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 aBlood 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.

• Regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE).

  Authors: Friedemann J Gückel, Gunnar Brix, Michael Hennerici, Robert Lucht, Christine Ueltzhöffer, Wolfgang Neff

  European radiology. 11/2007; 17(10):2483-90.

  The aim of the present study was a detailed analysis of the regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE) by means of functionalThe aim of the present study was a detailed analysis of the regional cerebral blood flow and blood volume in patients with subcortical arteriosclerotic encephalopathy (SAE) by means of functional magnetic resonance imaging (MRI). A group of 26 patients with SAE and a group of 16 age-matched healthy volunteers were examined. Using a well-established dynamic susceptibility contrast-enhanced MRI method, the regional cerebral blood flow (rCBF) and blood volume (rCBV) were quantified for each subject in 12 different regions in the brain parenchyma. As compared to healthy volunteers, patients with SAE showed significantly reduced rCBF and rCBV values in white matter regions and in the occipital cortex. Regions containing predominantly grey matter show almost normal rCBF and rCBV values. In conclusion, quantitative analysis of rCBF and rCBV values demonstrates clearly that SAE is a disease that is associated with a reduced microcirculation predominantly in white matter.

• Non-invasive assessment of vessel morphology and function in tumors by magnetic resonance imaging.

  Authors: Fabian Kiessling, Manfred Jugold, Eva C Woenne, Gunnar Brix

  European radiology. 09/2007; 17(8):2136-48.

  The switch to an angiogenic phenotype is an important precondition for tumor growth, invasion and spread. Since newly formed vessels are characterized by structural, functional and molecularThe switch to an angiogenic phenotype is an important precondition for tumor growth, invasion and spread. Since newly formed vessels are characterized by structural, functional and molecular abnormalities, they offer promising targets for tumor diagnosis and therapy. Previous studies indicate that MRI is valuable to assess vessel morphology and function. It can be used to distinguish between benign and malignant lesions and to improve delineation of proliferating areas within heterogeneous tumors. In addition, tracer kinetic analysis of contrast-enhanced image series allows the estimation of well-defined physiological parameters such as blood volume, blood flow and vessel permeability. Frequently, changes of these parameters during cytostatic, anti-angiogenic and radiation therapy precede tumor volume reduction. Moreover, target-specific MRI techniques can be used to elucidate the expression of angiogenic markers at the molecular level. This review summarizes strategies for non-invasive characterization of tumor vascularization by functional and molecular MRI, hereby introducing representative preclinical and clinical applications.

• Assessment of hepatic perfusion in transplanted livers by pharmacokinetic analysis of dynamic magnetic resonance measurements.

  Authors: Johann Scharf, Andre Kemmling, Thomas Hess, Arianeb Mehrabi, Guenter Kauffmann, Christoph Groden, Gunnar Brix

  Investigative radiology. 05/2007; 42(4):224-9.

  OBJECTIVE: The purpose of this study was to validate the assessment of hepatic perfusion by pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance image series. MATERIALS ANDOBJECTIVE: The purpose of this study was to validate the assessment of hepatic perfusion by pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance image series. MATERIALS AND METHODS: Dynamic measurements were performed with a saturation recovery turbo fast low angle shot (ie, FLASH) sequence over the course of approximately 4 minutes in 17 patients with transplanted livers. By pharmacokinetic analysis using an open 2-compartment model, we estimated and correlated an amplitude of signal enhancement, A, and the perfusion rate, kp, with invasive perfusion measurements from implanted thermo-diffusion probes (FTDP). RESULTS: Data analysis for segment IV of the transplanted livers yielded a mean blood flow of 81 +/- 19 mL/min/100g and a mean perfusion rate of 13 +/- 6 minutes. There was a significant correlation between FTDP and kp (rS = 0.64, P = 0.01) but not with A. CONCLUSIONS: Although our open 2-compartment model oversimplifies the complexity of hepatic perfusion, it allows a numerically robust estimation of regional blood flow per unit of blood volume. Thus, dynamic magnetic resonance imaging represents a noninvasive method to assess hepatic perfusion rate which can be visualized in color coded images.

• Impact of stroma on the growth, microcirculation, and metabolism of experimental prostate tumors.

  Authors: Christian M Zechmann, Eva C Woenne, Gunnar Brix, Nicole Radzwill, Martin Ilg, Peter Bachert, Peter Peschke, Stefan Kirsch, Hans-Ulrich Kauczor, Stefan Delorme, Wolfhard Semmler, Fabian Kiessling

  Neoplasia (New York, N.Y.). 02/2007; 9(1):57-67.

  In prostate cancers (PCa), the formation of malignant stroma may substantially influence tumor phenotype and aggressiveness. Thus, the impact of the orthotopic and subcutaneous implantations ofIn prostate cancers (PCa), the formation of malignant stroma may substantially influence tumor phenotype and aggressiveness. Thus, the impact of the orthotopic and subcutaneous implantations of hormone-sensitive (H), hormone-insensitive (HI), and anaplastic (AT1) Dunning PCa in rats on growth, microcirculation, and metabolism was investigated. For this purpose, dynamic contrast-enhanced magnetic resonance imaging and (1)H magnetic resonance spectroscopy ([(1)H]MRS) were applied in combination with histology. Consistent observations revealed that orthotopic H tumors grew significantly slower compared to subcutaneous ones, whereas the growth of HI and AT1 tumors was comparable at both locations. Histologic analysis indicated that glandular differentiation and a close interaction of tumor cells and smooth muscle cells (SMC) were associated with slow tumor growth. Furthermore, there was a significantly lower SMC density in subcutaneous H tumors than in orthotopic H tumors. Perfusion was observed to be significantly lower in orthotopic H tumors than in subcutaneous H tumors. Regional blood volume and permeability-surface area product showed no significant differences between tumor models and their implantation sites. Differences in growth between subcutaneous and orthotopic H tumors can be attributed to tumor-stroma interaction and perfusion. Here, SMC, may stabilize glandular structures and contribute to the maintenance of differentiated phenotype.

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

  Authors: Gunnar Brix, Robert Lucht, Jürgen Griebel

  Biomedizinische Technik. Biomedical engineering. 02/2006; 51(5-6):325-30.

  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 statusRapid 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.