BACKGROUND:Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium.METHODS:We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors and chemokine receptors of human bone marrow-derived Mesenchymal Stem Cells (MSC). Analyses included MSC functions in vitro, as well as homing and therapeutic efficacy in rodent models of central nervous system´s pathologies in vivo.FINDINGS:PEI treatment did not affect viability, immunomodulation or differentiation potential of MSC, but increased the CCR4 expression and functionally blocked their adhesion receptors, thus decreasing their adhesion capacity in vitro. Intravenously applied in a rat model of brain injury, the homing rate of PEI-MSC in the brain was highly increased with decreased numbers of adherent PEI-MSC in the lung vasculature. Moreover, in comparison to untreated MSC, PEI-MSC featured increased tumour directed migration in a mouse glioblastoma model, and superior therapeutic efficacy in a murine model of stroke.INTERPRETATION:Balanced stem cell adhesion and migration in different parts of the vasculature and tissues together with the local microenvironment impacts their therapeutic efficacy.FUNDING:Robert Bosch Stiftung, IZEPHA grant, EU grant 7 FP Health.

BACKGROUND:Stem cells` (SC) functional heterogeneity and its poorly understood aetiology impedes clinical development of cell-based therapies in regenerative medicine and oncology. Recent studies suggest a strong correlation between the SC migration potential and their therapeutic efficacy in humans. Designating SC migration as a denominator of functional SC heterogeneity, we sought to identify highly migrating subpopulations within different SC classes and evaluate their therapeutic properties in comparison to the parental non-selected cells.METHODS:We selected highly migrating subpopulations from mesenchymal and neural SC (sMSC and sNSC), characterized their features including but not limited to migratory potential, trophic factor release and transcriptomic signature. To assess lesion-targeted migration and therapeutic properties of isolated subpopulations in vivo, surgical transplantation and intranasal administration of MSCs in mouse models of glioblastoma and Alzheimer's disease respectively were performed.FINDINGS:Comparison of parental non-selected cells with isolated subpopulations revealed superior motility and migratory potential of sMSC and sNSC in vitro. We identified podoplanin as a major regulator of migratory features of sMSC/sNSC. Podoplanin engineering improved oncovirolytic activity of virus-loaded NSC on distantly located glioblastoma cells. Finally, sMSC displayed more targeted migration to the tumour site in a mouse glioblastoma model and remarkably higher potency to reduce pathological hallmarks and memory deficits in transgenic Alzheimer's disease mice.INTERPRETATION:Functional heterogeneity of SC is associated with their motility and migration potential which can serve as predictors of SC therapeutic efficacy.FUNDING:This work was supported in part by the Robert Bosch Stiftung (Stuttgart, Germany) and by the IZEPHA grant.

The aim of the study was to evaluate the diagnostic accuracy of carotid ultrasound (CU) to predict coronary atherosclerosis in asymptomatic male marathon runners. A total of 49 male marathon runners older than 45 years (mean age 53.3 ± 7.2 years, range 45‐74 years) received CU and cardiac CT angiography (CTA) including calcium scoring (CS). Results of CU and CTA were classified binary: 1. Absence of atherosclerosis and 2. Presence of atherosclerosis. The extent of atherosclerosis was not primary end point of the study. Mean PROCAM score was 2.3% (SD 2.2, range 0.44%‐12.34%). One person had to be excluded from analysis (one missing CT‐scan). From the remaining 48 marathon runners, 17 (35.4%) had carotid atherosclerosis and 22 (45.8%) coronary atherosclerosis. Atherosclerosis in either exam was diagnosed in 27/48 (56.3%) marathon runners. Diagnostic accuracy of CU to predict coronary atherosclerosis was: sensitivity 54.55% (95% CI 32.2‐75.6), specificity 80.8% (CI 60.6‐93.4), positive predictive value 70.6 (CI 44.1‐89.9), negative predictive value 67.7 (CI 48.6‐83.3) with a positive likelihood ratio of 2.84 (CI 1.18‐6.82) and a negative likelihood ratio of 0.56 (CI 0.34‐0.92). Coronary and/or carotid atherosclerosis can be detected in more than 50% of male marathon runners aged older than 45 years. The diagnostic value of carotid ultrasound to predict coronary atherosclerosis is low but higher than the accuracy of rest‐ or stress‐ECG. As outcome studies in sportsmen are still missing, the routine evaluation of the carotid arteries by ultrasound or even cardiac CT cannot be recommended at present. Furthermore, the incidence of atherosclerosis by our method in normal population is not known.

PURPOSE:The impact of preoperative MRI on re-excisions and mastectomy rate is discussed controversially in the literature. Aim of this study was to evaluate the effect of preoperative breast MRI on the surgical procedure and rate of repeated surgeries. MATERIAL AND METHODS:A total of 991 consecutive patients in the years 2009 and 2010 with 1036 primary breast cancers were retrospectively analyzed. Sixty percent (599 patients with 626 cancers) received preoperative breast MRI. Planned surgical procedures before and after MRI and numbers of repeated surgeries in patients with (MR+ ) and without preoperative MRI (MR-) were compared. RESULTS:The result of preoperative MRI changed the surgical procedure in 25% (157/626) of the cases. In 81% (127/157), MRI was beneficial for the patients, as otherwise occult carcinomas were removed (n=122) or further biopsy could be prevented (n=5). Mastectomy rates did not differ between MR+ and MR- group (39% vs. 39%). On multiple regression analysis, the MR+ group had a lower chance for repeated surgery (p<0.05). CONCLUSION:Preoperative MRI could lower the chance for repeated surgery in patients with primary breast cancer. The rate of mastectomy did not differ between patients undergoing preoperative MRI and those who did not.

Purpose: To evaluate the potential of gadolinium (Gd) as contrast material (CM) in second generation dual energy computed tomography (DECT).Material and methods: In a phantom model, DECT post-processing was used to increase Gd attenuation using advanced monoenergetic extrapolation (MEI), to create virtual non-contrast images (Gd-VNC) and Gd maps and to quantify Gd content. Dilutions of Gd and iodinated CM (7-296 HU) were filled in syringes, placed in an attenuation phantom and scanned with standard DECT protocols (80 &100/Sn140 kV). MEI (40-190 keV) and VNC images as well as Gd maps were computed. The amount of Gd Was quantified and the accuracy was compared to iodine images. Linear regression models were calculated to evaluate Gd attenuation of equivolume CM doses and clinical MRI doses.Results: Applying monoenergetic reconstructions and using Gd as contrast agent (Gd MEI 40 keV) doubled Hounsfield-Units (HU) and 90% of the SNR (averaged: 225 HU, SNR3.1) are achievable, as compared to iodinated CM at 120 kV (averaged:110 HU, SNR3.5), at Gd doses of 1.0 mmol/kg BW. The accuracies of Gd-VNC (deviation, 6 12 HU) images and Gd quantification (measurement error, 17%) were not significantly different to those of iodine enhanced images (VNC:deviation, 2 11 HU; measurement error,14%).Conclusion: Using monoenergetic extrapolation at 40 keV, it is possible to increase Gd-CM attenuation significantly. Thus, equivalent HU and half the SNR in comparison to a standard dose of ICM at 120 kV can be expected at a Gd-CM dose of 0.5 mmol/kg BW. Post-processing features of iodine based DECT like monoenergetic or VNC images, iodine maps or quantification of CM are feasible with the use of Gd-CM. (C) 2017 Elsevier Inc. All rights reserved.

The aim of this cohort study was to assess the risk of developing cancer, specifically leukaemia, tumours of the central nervous system and lymphoma, before the age of 15 years in children previously exposed to computed tomography (CT) in Germany. Data for children with at least one CT between 1980 and 2010 were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010 were identified by stochastic linkage with the German Childhood Cancer Registry (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed to assess the underlying medical conditions at time of the CT. Cases were only included if diagnosis occurred at least 2 years after the first CT and no signs of cancer were recorded in the radiology reports. Standardised incidence ratios (SIR) using incidence rates from the general population were estimated. The cohort included information on 71,073 CT examinations in 44,584 children contributing 161,407 person-years at risk with 46 cases initially identified through linkage with the GCCR. Seven cases had to be excluded due to signs possibly suggestive of cancer at the time of first CT. Overall, more cancer cases were observed (O) than expected (E), but this was mainly driven by unexpected and possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was 1.72 (95 % CI 0.89–3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI 0.54–2.78, O = 7). Despite careful examination of the medical information, confounding by indication or reverse causation cannot be ruled out completely and may explain parts of the excess. Furthermore, the CT exposure may have been underestimated as only data from the participating clinics were available. This should be taken into account when interpreting risk estimates.

OBJECTIVES The aim of our study was to evaluate the feasibility of detecting coronary artery lesions using a new computed tomography (CT) scanner with 16 detectors and faster gantry rotation. BACKGROUND Computed tomography angiography of the coronaries permits assessment of the coronaries; however, image quality is still impaired by motion artifacts and calcifications. METHODS Sixty patients scheduled for conventional coronary angiography (CCA) were additionally studied by multislice spiral computed tomography (MSCT). Calcium scores and a contrastenhanced visualization of the coronaries were performed and analyzed regarding evaluability, presence of coronary artery lesions, and correct clinical diagnosis. RESULTS Calcium scoring was successful in all patients; 58 of 60 patients had a diagnostic contrast-enhanced scan. Mean calcium score was 506 743 Agatston score equivalent (ASE); 13 of 58 (22%) patients had an ASE 1,000, 46 of 58 (78%) patients 1,000. In 763 coronary segments, CCA detected a total of 75 lesions 50%. The MSCT correctly assessed 54 of these. Twenty-one lesions were missed or incorrectly underestimated. Sensitivity was 72%, specificity 97%. When restricting analysis to patients with an ASE 1,000, 40 significant lesions 50% were seen on CCA, and MSCT correctly detected 39 lesions (sensitivity 98%, specificity 98%). Regardless of any threshold, the correct clinical diagnosis could be obtained in 58 of 60 (97%) of all patients. CONCLUSIONS In individuals with low-to-moderate amounts of coronary artery calcium, 16-detector CT coronary angiography has high sensitivity and specificity for the diagnosis of significant coronary artery stenosis. (J Am Coll Cardiol 2004;44:1230–7) © 2004 by the American College of Cardiology Foundation

Ziel dieser Studie war es herauszufinden, ob sich bei Prädiabetikern Zusammenhänge zwischen der Ausprägung verschiedener Fettkompartimente und ektoper Fetteinlagerungen sowie der systemischen Low-Grade-Inflammation und Insulinsensitivität feststellen lassen.

Background Previous studies have shown a benefit of magnetic resonance (MR)-diffusion-weighted imaging (DWI) for follow-up after liver radiofrequency (RF) ablation. However, no data are available concerning acute changes of DWI characteristics immediately after RF ablation. Purpose To analyze and compare the MR-diffusion characteristics of pre-interventional hepatic malignancies and the ablation zone during successful MR-guided RF ablation. Material and Methods This retrospective study was conducted in accordance with the guidelines of the local institutional review board. Forty-seven patients with 29 HCC (24 patients) and 30 hepatic metastases (23 patients) underwent MR-guided radiofrequency ablation including DWI before and immediately after ablation (b = 50, 400, 800 s/mm2). Two reviewers (A and B) analyzed DWI with focus on detectability of the tumor before ablation and characteristics of the coagulative area after treatment. Mean apparent diffusion coefficient (ADC) was compared between liver, untreated tumor, and hyperintense areas in post-ablative DWI (b = 800 s/mm2) with the paired Student’s t-test. Results Pre-ablative: the reviewers classified 19/29 (A) and 23/29 (B) HCC and 25/30 (A and B) metastases as detectable in DWI. Post-ablative: a hyperintense rim surrounding the ablation zone was observed in 28/29 treated HCC and 30/30 treated metastases (A and B). A homogenous hypointense central ablation zone was found in 18/29 (A) and 20/29 (B) treated HCC and 17/30 (A & B) treated metastases in DWI. ADC of the rim was significantly lower than ADC of the liver ( P < 0.001). Conclusion DWI enables visualization of the target tumor in MR-guided liver radiofrequency ablation in most cases. A common post-ablative DWI finding is a hyperintense rim with decreased ADC surrounding the ablation zone.

Objective: This prospective study assesses volume changes of the Achilles tendon in case of chronic tendinopathy (TEN), using an automated contour detection algorithm in submillimeter isotropic 3-dimensional magnetic resonance imaging data sets, recorded at 3 T.Methods: Forty-one subjects (median age, 40 years; range, 19-68 years) were included in this prospective study and underwent nonenhanced magnetic resonance imaging of both Achilles tendons at 3 T, deploying a T2-weighted 3-dimensional Fast-Spin-Echo sequence with submillimeter resolution of 0.8mm. Of the 41 subjects, 13 were classified as patients with TEN and 28 were healthy volunteers and served as control group. Of the 13 patients, 10 had unilateral TEN and 3 had bilateral TEN. Achilles tendons were automatically segmented in the T2-weighted magnetic resonance data sets for the evaluation of the tendon volume (0-3 cm proximal to the cranial border of the calcaneal bone). The total volume (length, 3 cm) was divided in 3 subvolumes of 1 cm length, named volume (0-1 cm), volume (12 cm), and volume (2-3 cm). Minimum and maximum tendon cross-sectional area within the total volume was processed. A standardized pain questionnaire was obtained from all patients.Results: The automated contour detection algorithm worked reliably in all cases. The TEN group showed a significantly increased tendon volume compared to the control group (mean volume, 2.94 vs 2.43 mm(3); P < 0.05). The difference was most obvious concerning volume (2-3 cm) (P < 0.0001). Evaluation of clinical severity revealed a moderate correlation between VISA-score and tendon volume (2-3 cm) as well as the maximum/minimum tendon area (rho = -0.44, rho = -0.48, and rho = -0.41). In case of unilateral TEN, the symptomatic side showed an increased tendon volume (2-3 cm) and increased minimum area (P < 0.05).Conclusions: Tendon volume and size are adequate surrogate parameters to differentiate patients with chronic TEN from healthy subjects, and may discriminate symptomatic TEN from asymptomatic "silent" TEN in patients with unilateral symptoms.

OBJECTIVE. Dual-energy CT (DECT) enables subtraction of calcium, facilitating the visualization of bone marrow (BM) in the axial skeleton. The purpose of this study was to assess whether DECT BM images have the potential to improve the detection of multifocal and diffuse BM infiltration in multiple myeloma (MM) in comparison with regular CT with MRI as the reference standard. SUBJECTS AND METHODS. This study included 32 consecutive patients who had known MM or presented with monoclonal gammopathy of unknown significance and underwent DECT and MRI of the axial skeleton. The degrees (none, n = 14; moderate, n = 10; and high, n = 8) and patterns (diffuse, n = 10 or multifocal, n = 8) of infiltration were assessed on MR images. Attenuation in BM and CT images in known uninvolved and involved areas was measured. Cutoff values of attenuation in BM images for infiltration in lytic and nonlytic lesions were established by ROC analysis. At least 120 days later, sensitivity and specificity for reading CT images alone and when using additional BM images were evaluated. RESULTS. ROC analysis revealed larger AUC in BM images than in CT images; cutoff values for marrow invasion in BM images were 4 and -3 HU in lytic and nonlytic lesions, respectively. In the blinded reading session, BM images improved the sensitivity for the detection of diffuse infiltration from 0 to as much as 75% for cases with high-grade infiltration. In multifocal patterns, BM images did not significantly change the detection rate. CONCLUSION. BM images have the potential to improve the sensitivity for detection of diffuse BM involvement in comparison with regular CT.

Abstract Purpose: To evaluate the prevalence of coronary artery disease (CAD) in middle-aged, male marathon runners using coronary dual source CT angiography (DSCTA). Materials and Methods: 50 male marathon runners older than 45 years (mean age: 52.7, standard deviation: 5.9 years, range: 45 to 67 years) received DSCTA including calcium scoring (CS) in addition to standard pre-participation screening. Based on standard risk factors, the risk for coronary events was calculated using the PROCAM score. Coronary status was defined using the following system: 1. absence of CAD (CS zero, no coronary plaques) 2. mild coronary atherosclerosis (CS > 0, coronary plaques with luminal narrowing < 50 %), 3. moderate coronary atherosclerosis (CS > 0, luminal narrowing > 50 %), 4. significant CAD (CS > 0, luminal narrowing > 75 %). Results: The mean PROCAM score was 1.85 % (standard deviation = 1.56, range 0.39 to 8.47 %). 26/50 marathon runners had no atherosclerosis. 1 of the remaining 24 participants had significant CAD, 3 had moderate coronary atherosclerosis and 20 had mild coronary atherosclerosis. Treadmill exercise testing was unremarkable in terms of myocardial ischemia in all participants. Age, systolic blood pressure, personal minimum time, family history of cardiovascular disease and PROCAM score were factors associated with an increased risk for coronary atherosclerosis. Conclusion: Coronary atherosclerosis can be detected in almost 50 % of male marathon runners aged older than 45 years. In 24 % of the participants plaques were located in the proximal coronary system. However, only a minority of these persons have obstructive CAD. As expected, treadmill exercise testing failed to detect these persons that possibly have a higher risk for coronary events. Key points: • Coronary atherosclerosis can be detected in ~50 % of male marathon runners > 45 years • Only a minority of these persons have obstructive CAD • Treadmill exercise testing failed to detect these persons • Cardiac CT might help to identify athletes with elevated risk for coronary events, especially in persons with a family history of coronary artery disease Citation Format: • Tsiflikas I, Thomas C, Fallmann C et al. Prevalence of Subclinical Coronary Artery Disease in Middle-Aged, Male Marathon Runners Detected by Cardiac CT. Fortschr Röntgenstr 2015; 187: 561 – 568

Background Three-vessel coronary artery disease (CAD) comes along with globally reduced myocardial perfusion potentially restricting the demarcation of regional hypoperfusion in stress perfusion cardiac magnetic resonance imaging (MRI). Purpose To evaluate whether stress perfusion cardiac MRI is capable of detecting myocardial hypoperfusion in patients with 3-vessel CAD reliably. Material and Methods Two hundred and five patients with symptoms of CAD were included. The examination protocol comprised imaging of myocardial perfusion at stress (0.14 mg/kg/min adenosine for 4 min) using a 2D saturation recovery gradient echo sequence after administration of gadobutrol (0.1 mmol/kg body weight). Perfusion sequences were assessed qualitatively by two experienced observers. Coronary angiography served as standard of reference. Results Sensitivity and specificity for hemodynamically relevant stenoses in patients with 0-, 1-, 2-, 3-vessel coronary artery disease were 100%/91%, 91%/73%, 90%/71%, 92%/64%; positive/negative predictive value, 67%/100%, 91%/73%, 83%/81%, 93%/58%; diagnostic accuracy, 93%/87%/83%/87%, respectively. The negative predictive value in patients with 3-vessel CAD was lower than in patients with 0- and 2-vessel CAD and the specificity lower than in patients with no CAD whereas the positive predictive value was higher than in patients with no CAD. The other proportions did not differ significantly between the groups. Conclusion The diagnostic value of stress perfusion cardiac MRI in patients with 3-vessel CAD is comparable to results in patients with 1- or 2-vessel CAD. In the rare event that stress perfusion images do not depict regional hypoperfusion in patients with severe 3-vessel CAD, myocardial ischemia could be identified by reduced semi-quantitative perfusion parameters.

Rationale and Objectives: Automatic bone and plaque subtraction (BPS) in computed tomographic angiographic (CTA) examinations using dual-energy CT (DECT) remains challenging because of beam-hardening artifacts in the shoulder region and close proximity of the internal carotid artery to the base of the skull. The selection of the tube voltage combination in dual-source CT influences the spectral separation and the susceptibility for artifacts. The purpose of this study was to assess which tube voltage combination leads to an optimal image quality of head and neck DECT angiograms after bone subtraction.Materials and Methods: Fifty-one patients received tin-filter-enhanced DECT angiograms of the-supra-aortic arteries using two voltage protocols: 24 patients were studied using 80/Sn140 kV and 27 using a 100/Sn140 kV protocol, both protocols with an additional tin filter. A commercially available DE-CTA BPS algorithm was used. Artificial vessel erosions in BPS maximum intensity projections (four-level Likert scale with CTA source data as reference) and vessel signal-to-noise ratio (SNR) were assessed in the level of the shoulders and the base of the skull in each patient and compared.Results: At the level of the shoulder, 100/Sn140 kV achieved higher SNR (23.4 +/- 6.4 at 80/Sn140 kV vs. 35.1 +/- 11.8 at 100/Sn140 kV; P < .0001) with less erosions (erosion score 3.9 +/- 0.4 in 80/Sn140 kV vs. 2.1 +/- 1.3 in 100/Sn140 kV; P < .0001) than 80/Sn140 kV. At the level-of the skull base, erosion scores and objective image quality of arterial segments were comparable with both protocols (P = .14).Conclusions: The 100/Sn140 kV protocol achieved more favorable results for BPS of the supra-aortic arteries than the 80/Sn140 kV protocol.

Direct stem cell therapies for functionally impaired tissue require a sufficient number of cells in the target region and a method for verifying the fate of the cells in the subsequent time course. In vivo MRI of iron labeled mesenchymal stem cells has been suggested to comply with these requirements. The study was conducted to evaluate proliferation, migration, differentiation and adhesion effects as well as the obtained iron load of an iron labeling strategy for mesenchymal stem cells. After injection into the porcine urethral sphincter, the labeled cells were monitored for up to six months using MRI.Mesenchymal stem cells were labeled with ferucarbotran (60/100/200 µg/mL) and ferumoxide (200 µg/mL) for the analysis of migration and viability. Phantom MR measurements were made to evaluate effects of iron labeling. For short and long term studies, the iron labeled cells were injected into the porcine urethral sphincter and monitored by MRI. High resolution anatomical images of the porcine urethral sphincter were applied for detection of the iron particles with a turbo‐spin‐echo sequence and a gradient‐echo sequence with multiple TE values. The MR images were then compared with histological staining.The analysis of cell function after iron labeling showed no effects on proliferation or differentiation of the cells. Although the adherence increases with higher iron dose, the ability to migrate decreases as a presumed effect of iron labeling.The iron labeled mesenchymal stem cells were detectable in vivo in MRI and histological staining even six months after injection.Labeling with iron particles and subsequent evaluation with highly resolved three dimensional data acquisition allows sensitive tracking of cells injected into the porcine urethral sphincter for several months without substantial biological effects on mesenchymal stem cells. Copyright © 2015 John Wiley & Sons, Ltd.

Unter multiparametrischer Bildgebung versteht man die Akquisition mehrerer Bilddatensatze unterschiedlichen Informationsinhaltes innerhalbeiner einzelnen Untersuchung.

Die MR/PET ermöglicht als Hybridverfahren die Akquisition einer Vielzahl von Parametern während einer einzelnen Untersuchung. Dazu gehören die Darstellung der Anatomie, aber auch funktioneller und metabolischer Informationen, etwa zu Perfusion, Diffusion und Stoffwechsel.

Deep venous thrombosis (DVT) can be difficult to detect using CT due to poor and heterogeneous contrast. Dual-energy CT (DECT) allows iodine contrast optimization using noise-optimized monoenergetic extrapolations (MEIs) and iodine maps (IMs). Our aim was to assess whether MEI and IM could improve the delineation of thrombotic material within iodine-enhanced blood compared to single-energy CT (SECT).