Intratumoral heterogeneity after targeted therapy in murine cancer models with differing degrees of malignancy.

INTRODUCTION: Conventional morphologic and volumetric assessment of treatment response is not suitable for adequately assessing responses to targeted cancer therapy. The aim of this study was to evaluate changes in tumor composition after targeted therapy in murine models of breast cancer with differing degrees of malignancy via non-invasive magnetic resonance imaging (MRI). MATERIALS AND METHODS: Mice bearing highly malignant 4T1 tumors or low malignant 67NR tumors were treated with either a combination of two immune checkpoint inhibitors (ICI, anti-PD1 and anti-CTLA-4) or the multi-tyrosine kinase inhibitor sorafenib, following experiments with macrophage-depleting clodronate-loaded liposomes and vessel-stabilizing angiopoietin-1. Mice were imaged on a 9.4 T small animal MRI system with a multiparametric (mp) protocol, comprising T1 and T2 mapping and diffusion-weighted imaging. Tumors were analyzed ex vivo with histology. RESULTS AND DISCUSSIONS: All treatments led to an increase in non-viable areas, but therapy-induced intratumoral changes differed between the two tumor models and the different targeted treatments. While ICI treatment led to intratumoral hemorrhage, sorafenib treatment mainly induced intratumoral necrosis. Treated 4T1 tumors showed increasing and extensive areas of necrosis, in comparison to 67NR tumors with only small, but also increasing, necrotic areas. After either of the applied treatments, intratumoral heterogeneity, was increased in both tumor models, and confirmed ex vivo by histology. Apparent diffusion coefficient with subsequent histogram analysis proved to be the most sensitive MRI sequence. In conclusion, mp MRI enables to assess dedicated therapy-related intratumoral changes and may serve as a biomarker for treatment response assessment.

Sex-specifics of ECT outcome.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. METHODS: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). RESULTS: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. CONCLUSION: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

Forensic age assessment by 3.0 T MRI of the wrist: adaption of the Vieth classification.

OBJECTIVES: In order to find a reliable method to correctly assess majority in both sexes by MRI, a study was conducted to evaluate the applicability of the recently presented Vieth classification in wrist MRI, after it had originally been proposed for knee MRI. METHODS: After receiving a positive vote by the ethics committee, the left-hand wrists of 347 male and 348 female volunteers of German nationality in the age bracket 12-24 years were scanned. Before conducting the prospective, cross-sectional examinations, an informed consent was obtained from each volunteer. A 3.0 T MRI scanner was used, acquiring a T1 turbo spin-echo sequence (TSE) and a T2 TSE sequence with fat suppression by spectral presaturation with inversion recovery (SPIR). The images were assessed by applying the Vieth classification. Minimum, maximum, mean ± standard deviation, and median with lower and upper quartiles were defined. Intra- and interobserver agreements were determined by calculating the kappa coefficients. Differences between the sexes were analyzed using the Mann-Whitney U test. RESULTS: By applying the unmodified Vieth classification with corresponding schematics, it was possible to assess majority in both sexes via the epiphyseal-diaphyseal fusion of the distal radius and in males also via the epiphyseal-diaphyseal fusion of the distal ulna. The Mann-Whitney U test implied significant sex-related differences for all stages. For both epiphyses, the intra- and interobserver agreement levels were very good (κ > 0.8). CONCLUSION: If confirmed by further studies, it would be possible to determine the completion of the 18th year of life in both sexes by 3.0 T MRI of the wrist and using the Vieth classification. KEY POINTS: • The Vieth classification allows determining majority in males and females alike based on the distal radius' epiphysis by 3.0 T MRI of the wrist. • The Vieth classification also allows determining majority in males based on the distal ulna's epiphysis by 3.0 T MRI of the wrist, but not in females. • The presented data can be deemed referential within certain discussed boundaries.

Biventricular myocardial strain analysis using cardiac magnetic resonance feature tracking (CMR-FT) in patients with distinct types of right ventricular diseases comparing arrhythmogenic right ventricular cardiomyopathy (ARVC), right ventricular outflow-tract tachycardia (RVOT-VT), and Brugada syndrome (BrS).

OBJECTIVES: As underlying heart diseases of right ventricular tachyarrhythmias, ARVC causes wall-motion abnormalities based on fibrofatty myocardial degeneration, while RVOT-VT and BrS are thought to lack phenotypic MR characteristics. To examine whether cardiac magnetic resonance (CMR) feature tracking (FT) in addition to ARVC objectively facilitates detection of myocardial functional impairments in RVOT-VT and BrS. METHODS: Cine MR datasets of four retrospectively enrolled, age-matched study groups [n = 65; 16 ARVC, 26 RVOT-VT, 9 BrS, 14 healthy volunteers (HV)] were independently assessed by two distinctly experienced investigators regarding myocardial function using CMR-FT. Global strain (%) and strainrate (s-1) in radial and longitudinal orientation were assessed at RVOT as well as for left (LV) and right (RV) ventricle at a basal, medial and apical section with the addition of a biventricular circumferential orientation. RESULTS: RV longitudinal and radial basal strain (%) in ARVC (- 12.9 ± 4.2; 11.4 ± 5.1) were significantly impaired compared to RVOT-VT (- 18.0 ± 2.5, p ≤ 0.005; 16.4 ± 5.2, p ≤ 0.05). Synergistically, RVOT endocardial radial strain (%) in ARVC (33.8 ± 22.7) was significantly lower (p ≤ 0.05) than in RVOT-VT (54.3 ± 14.5). For differentiation against BrS, RV basal and medial radial strain values (%) (13.3 ± 6.1; 11.8 ± 2.9) were significantly reduced when compared to HV (21.0 ± 6.9, p ≤ 0.05; 20.1 ± 6.6, p ≤ 0.005), even in case of a normal RV ejection fraction (EF) (> 45%; n = 6) (12.0 ± 2.7 vs. 20.1 ± 6.6, p ≤ 0.05). CONCLUSIONS: CMR-FT facilitates relevant differentiation in patients with right ventricular tachyarrhythmias: between ARVC against RVOT-VT and HV as well as between BrS with even a preserved EF against HV.

Low rates of recanalization for wide-necked aneurysms treated with stenting after balloon-assisted coiling: combination of techniques delivers stable and improved results during follow-up.

PURPOSE: In the treatment of wide-necked aneurysms, stenting may be required after balloon-assisted coiling (BAC) for reconstructing the lumen/flow of the parent artery in cases of coil herniation. The potential benefits and complications of both techniques remain unclear when used together. Our aim was to assess the safety and long-term angiographic outcomes of stenting after BAC. METHODS: Retrospective review of 87 unruptured wide necked aneurysms (in 80 patients) treated with BAC and requiring stent placement at the final stage of the procedure due to coil prolapse. Aneurysm characteristics, technical issues, clinical records, and MR results were assessed. Post-treatment and follow-up angiograms were evaluated by two independent reviewers and categorized as "stable," "further thrombosis," or "recanalization." RESULTS: The mean maximum diameter was 9.1 ± 4.7 mm and aspect ratio 1.20 ± 0.47. Complete and near-complete initial occlusion were observed in 53 (60.9%) and 28 (32.2%) of all treated aneurysms, respectively. Angiographic follow-up (80 aneurysms; mean, 34.68 ± 25.26 months) revealed stability and further thrombosis in 92.4% (74/80). Recanalization was observed in six cases (7.5%, 6/83), four of which were retreated. No significantly different outcomes were found in terms of aneurysm size (p = 0.641). Transient and reversible procedure-related complications occurred in eight (9.2%), minor permanent deficits in 2.3%, and major deficits, including death, in four cases (4.6%). CONCLUSION: Our results suggest that treatment of wide-necked aneuryms with stent placement after BAC yields low recanalization rates and enhanced angiographic outcomes in long-term follow-up.

[Impact of anamnestic information and neurological deficits on the detection rate of secondary headaches]. / Einfluss von Anamnese und neurologischer Untersuchung auf die Detektionsrate sekundärer Kopfschmerzursachen.

PURPOSE: Headaches are a very common symptom and imaging is important to rule out symptomatic causes. For clinical differentiation between primary and secondary headaches an exact anamnesis and neurological examination are important. The aim of this study is therefore to identify anamnestic and neurological information that is associated with secondary headaches. Moreover, this study gives an overview of the causes and differential diagnoses of secondary headaches. METHODS: We performed a retrospective analysis of 239 patients ≥18 years with headaches who had undergone computed tomography or magnetic resonance imaging. The impact of basic characteristics such as age and gender as well as anamnestic (pain intensity, thromboembolic risk profile) and clinical information (neurological deficit, papilledema, reduced vigilance) was tested by χ2 test at the significance level p < 0.05. RESULTS: In all, 27 of the included patients (11.3%) showed intracranial pathologies that required treatment. The most frequent pathologies were intracranial hypertension (9 patients), cerebral mass lesions (7 patients) and thrombosis of the cranial sinus/veins (3 patients). There was a significant association of a pathologic imaging finding and neurological deficits (p = 0.001) and a papilledema (p < 0.001). Reduced vigilance, pain intensity and thromboembolic risk factors as well as age and gender showed no significant association. CONCLUSIONS: A neurological deficit and especially papilledema are hints towards secondary headaches and should result in computed tomography or magnetic resonance imaging. Other factors such as reduced vigilance, pain intensity, age and gender have no relevant impact on the occurrence of intracranial pathologies.

Magnetic resonance imaging-based evaluation of ossification of the medial clavicular epiphysis in forensic age assessment.

Evaluation of the degree of ossification of the medial clavicular epiphysis plays a crucial role in determining with an adequate degree of probability whether legally relevant age boundaries after the age of 17 have been crossed. In view of the need to avoid unnecessary radiation exposure, establishing non-X-ray methods for investigating the clavicle has long been a key objective in forensic age assessment research. Based on magnetic resonance imaging examinations in a large sample of healthy subjects, the current study for the first time presents statistical measures which allow inferences to be drawn for forensic age assessment in both sexes. We undertook a prospective study of a reference sample of 334 female and 335 male German volunteers aged from 12 to 24 using a 3-T MRI scanner. A 3D FFE (fast field echo) T1-weighted sequence with fat saturation was acquired. To stage ossification of the medial clavicular epiphysis, we used the clavicular ossification staging systems described by Schmeling et al. and Kellinghaus et al. Ossification stage IIIc offers a means in both sexes of demonstrating that the age of 18 has been attained prior to complete ossification of the epiphyseal plate. In both sexes, if a subject has reached ossification stage IV, it can be stated that he or she has attained the age of 21. Magnetic resonance imaging is a valid diagnostic procedure for determining the ossification stage of the medial clavicular epiphysis.

The impact of lesion location on dysphagia incidence, pattern and complications in acute stroke. Part 2: Oropharyngeal residue, swallow and cough response, and pneumonia.

BACKGROUND AND PURPOSE: Dysphagia is a well-known complication of acute stroke. Given the complexity of cerebral swallowing control it is still difficult to predict which patients are likely to develop swallowing dysfunction based on their neuroimaging. In Part 2 of a comprehensive voxel-based imaging study, whether the location of a stroke lesion can be correlated with further dysfunctional swallowing patterns, pulmonary protective reflexes and pneumonia was evaluated. METHODS: In all, 200 acute stroke cases were investigated applying flexible endoscopic evaluation of swallowing within 96 h from admission. Lesions were mapped using patients' computed tomography/magnetic resonance images and these were registered to a standard space. The percentage of lesioned volume of 137 anatomically defined brain regions was determined on a voxel basis (FSL5.0). Region-specific odds ratios (ORs) were calculated with respect to the presence of oropharyngeal residue, delayed swallow response, insufficient cough reflex and occurrence of pneumonia during hospital stay. Colour-coded lesion location maps of brain regions with significant ORs were created (P < 0.05). RESULTS: Lesion maps for residue and impaired swallow response depicted parietal-temporal areas of the right hemisphere. Limbic structures in the right hemisphere and sensory regions on the left were associated with cough reflex disturbance. There was no overlap of lesion maps for impaired swallow response and insufficient cough reflex or pneumonia, but substantial overlap between the last two conditions. CONCLUSIONS: This study gives new insights on the cortical representation of single components of swallowing and airway protection behaviours. The lesion model may help to risk-stratify patients for dysphagia and pneumonia based on their brain scan.

Effects of electroconvulsive therapy on amygdala function in major depression - a longitudinal functional magnetic resonance imaging study.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, little is known regarding brain functional processes mediating ECT effects. METHOD: In a non-randomized prospective study, functional magnetic resonance imaging data during the automatic processing of subliminally presented emotional faces were obtained twice, about 6 weeks apart, in patients with major depressive disorder (MDD) before and after treatment with ECT (ECT, n = 24). Additionally, a control sample of MDD patients treated solely with pharmacotherapy (MED, n = 23) and a healthy control sample (HC, n = 22) were obtained. RESULTS: Before therapy, both patient groups equally showed elevated amygdala reactivity to sad faces compared with HC. After treatment, a decrease in amygdala activity to negative stimuli was discerned in both patient samples indicating a normalization of amygdala function, suggesting mechanisms potentially unspecific for ECT. Moreover, a decrease in amygdala activity to sad faces was associated with symptomatic improvements in the ECT sample (r spearman = -0.48, p = 0.044), and by tendency also for the MED sample (r spearman = -0.38, p = 0.098). However, we did not find any significant association between pre-treatment amygdala function to emotional stimuli and individual symptom improvement, neither for the ECT sample, nor for the MED sample. CONCLUSIONS: In sum, the present study provides first results regarding functional changes in emotion processing due to ECT treatment using a longitudinal design, thus validating and extending our knowledge gained from previous treatment studies. A limitation was that ECT patients received concurrent medication treatment.

Prefrontal gray matter volume mediates genetic risks for obesity.

Genetic and neuroimaging research has identified neurobiological correlates of obesity. However, evidence for an integrated model of genetic risk and brain structural alterations in the pathophysiology of obesity is still absent. Here we investigated the relationship between polygenic risk for obesity, gray matter structure and body mass index (BMI) by the use of univariate and multivariate analyses in two large, independent cohorts (n=330 and n=347). Higher BMI and higher polygenic risk for obesity were significantly associated with medial prefrontal gray matter decrease, and prefrontal gray matter was further shown to significantly mediate the effect of polygenic risk for obesity on BMI in both samples. Building on this, the successful individualized prediction of BMI by means of multivariate pattern classification algorithms trained on whole-brain imaging data and external validations in the second cohort points to potential clinical applications of this imaging trait marker.

Magnetic resonance imaging of the distal radial epiphysis: a new criterion of maturity for determining whether the age of 18 has been completed?

To improve the accuracy of forensic age estimation where there is no legal basis for carrying out x-ray examinations, it would be useful to establish non-x-ray imaging techniques. The objective of this study was to provide reference data for the magnetic resonance imaging-based evaluation of the ossification stage of the distal radius. Furthermore, we tested a new criterion of the maturity of the distal radial epiphysis for determining whether an individual has completed the age of 18. We investigated 668 MRI scans of the distal radial epiphysis from 333 female and 335 male subjects ranging in age from 12 to 24. To determine the ossification stage, we used the clavicular ossification staging systems described by Schmeling et al. and Kellinghaus et al. Ossification stage IV as described by Schmeling et al. was divided into two sub-stages, IVa and IVb, depending on whether or not it was possible to identify a triple-banded meta-epiphyseal zone of calcification. All study subjects were able to be assigned to an ossification stage without ambiguity. We present statistics relating to the distribution of ossification stages divided by sex. The age of the youngest female subject assessed as ossification stage IVb was 16.8, the age of the youngest male subject 18.6. The youngest age at which female subjects were assessed as ossification stage V was 22.3; for male subjects it was 23.1. Further independent studies should be carried out to determine whether ossification stage IVb can indeed be used to reliably determine whether a male subject has completed the age of 18.

TNF receptors 1 and 2 exert distinct region-specific effects on striatal and hippocampal grey matter volumes (VBM) in healthy adults.

Tumour necrosis factor alpha (TNFα) has been implicated in the pathophysiology of neurodegenerative and neuropsychiatric disease, with research highlighting a role for TNFα in hippocampal and striatal regulation. TNFα signals are primarily transduced by TNF receptors 1 and 2 (TNFR1 and TNFR2), encoded by TNFRSF1A and TNFRSF1B, which exert opposing effects on cell survival (TNFR1, neurodegenerative; TNFR2, neuroprotective). We therefore sought to explore the respective roles of TNFR1 and TNFR2 in the regulation of hippocampal and striatal morphology in an imaging genetics study. Voxel-based morphometry was used to analyse the associations between TNFRSF1A (rs4149576 and rs4149577) and TNFRSF1B (rs1061624) genotypes and grey matter structure. The final samples comprised a total of 505 subjects (mean age = 33.29, SD = 11.55 years; 285 females and 220 males) for morphometric analyses of rs1061624 and rs4149576, and 493 subjects for rs4149577 (mean age = 33.20, SD = 11.56 years; 281 females and 212 males). Analyses of TNFRSF1A single nucleotide polymorphisms (SNPs) rs4149576 and rs4149577 showed highly significant genotypic associations with striatal volume but not the hippocampus. Specifically, for rs4149576, G homozygotes were associated with reduced caudate nucleus volumes relative to A homozygotes and heterozygotes, whereas for rs4149577, reduced caudate volumes were observed in C homozygotes relative to T homozygotes and heterozygotes. Analysis of the TNFRSF1B SNP rs1061624 yielded a significant association with hippocampal but not with striatal volume, whereby G homozygotes were associated with increased volumes relative to A homozygotes and heterozygotes. Our findings indicate a role for TNFR1 in regulating striatal but not hippocampal morphology, as well as a complementary role for TNFR2 in hippocampal but not in striatal morphology.

Digital mammography screening: sensitivity of the programme dependent on breast density.

OBJECTIVES: To analyse the impact of breast density on the sensitivity of a population-based digital mammography screening programme (SP) as key evaluation parameter. METHODS: 25,576 examinations were prospectively stratified from ACR category 1 to 4 for increments of 25 % density during independent double reading. SP was calculated as number of screen-detected cancers divided by the sum of screen-detected plus interval cancers (24-months period) per ACR category, related to the first reading (a), second reading (b) and highest stratification if discrepant (c). Chi-square tests were used for comparison. RESULTS: Overall sensitivity of the programme was 79.9 %. SP in ACR 4 (a: 50 %, b: 50 %, c: 50 %) was significantly lower than in ACR 3 (a: 72.9 %, b: 79.4 %, c: 80.7 %, p < 0.001), ACR 2 (a: 83.9 %, b: 85.7 %, c: 83.2 %, p < 0.001) and ACR 1 (a: 100 %, b: 88.8 %, c: 100 %; p < 0.001). Frequencies of ACR 4 were a: 5.0 %, b: 4.3 %, c: 6.9 %. CONCLUSION: Digital mammography screening with independent double reading leads to a high overall SP. In the small group of women with breast density classified as ACR 4 SP is significantly reduced compared to all other ACR categories. KEY POINTS: • Overall sensitivity of a population-based digital mammography screening programme (SP) was 79.9 %. • In women with ACR 1, 2, or 3, SP ranged between 72.9 %-100 %. • ACR 4 was rare in participants (<7 %) and SP was only 50 %. • SP in ACR 4 differed significantly from ACR 3 (p < 0.001).

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Impact of the Implementation of Thrombectomy with Stent Retrievers on the Frequency of Hemicraniectomy in Patients with Acute Ischemic Stroke.

BACKGROUND: The increasing use of endovascular treatments has led to higher recanalization rates and better clinical outcomes compared with intravenous thrombolysis alone. Stent retrievers represent the latest development for recanalization of large vessel occlusions. Decompressive hemicraniectomy has proved beneficial in patients suffering from rising intracranial pressure after malignant stroke. AIMS AND/OR HYPOTHESIS: We investigated the effect of the implementation of stent retriever treatment on the frequency of hemicraniectomy as a surrogate marker for infarct size and thus for poor neurological outcome. METHODS: Patients with acute ischemic stroke were retrospectively studied. We compared the frequency of hemicraniectomy following proximal artery occlusion of the internal carotid artery and middle cerebral artery main stem in the years before (2009 and 2010) and after (2012 and 2013) introducing stent retrievers. RESULTS: Overall, 497 patients with proximal arterial occlusion were included in the study. Of 253 patients admitted in the years 2009 and 2010 44 (17.4 %) and of 244 patients admitted in 2012 and 2013, 20 (8.2 %) received a hemicraniectomy. This decrease in the proportion of hemicraniectomies was statistically significant (p < 0.01). CONCLUSIONS: The findings in this study illustrate a significantly reduced rate of hemicraniectomies in patients with proximal artery occlusions after implementation of thrombectomy with stent retriever. Hereby, we could show a significant reduction of malignant infarctions after thrombectomy with stent retriever.

Pneumatic Distension of Ventricular Mural Architecture Validated Histologically.

Purpose: There are ongoing arguments as to how cardiomyocytes are aggregated together within the ventricular walls. We used pneumatic distension through the coronary arteries to exaggerate the gaps between the aggregated cardiomyocytes, analyzing the pattern revealed using computed tomography, and validating our findings by histology. Methods: We distended 10 porcine hearts, arresting 4 in diastole by infusion of cardioplegic solutions, and 4 in systole by injection of barium chloride. Mural architecture was revealed by computed tomography, measuring also the angulations of the long chains of cardiomyocytes. We prepared the remaining 2 hearts for histology by perfusion with formaldehyde. Results: Increasing pressures of pneumatic distension elongated the ventricular walls, but produced insignificant changes in mural thickness. The distension exaggerated the spaces between the aggregated cardiomyocytes, compartmenting the walls into epicardial, central, and endocardial regions, with a feathered arrangement of transitions between them. Marked variation was noted in the thicknesses of the parts in the different ventricular segments, with no visible anatomical boundaries between them. Measurements of angulations revealed intruding and extruding populations of cardiomyocytes that deviated from a surface-parallel alignment. Scrolling through the stacks of tomographic images revealed marked spiraling of the aggregated cardiomyocytes when traced from base to apex. Conclusion: Our findings call into question the current assumption that cardiomyocytes are uniformly aggregated together in a tangential fashion. There is marked heterogeneity in the architecture of the different ventricular segments, with the aggregated units never extending in a fully transmural fashion. Key Points: • Pneumographic computed tomography reveals an organized structure of the ventricular walls.• Aggregated cardiomyocytes form a structured continuum, with marked regional heterogeneity.• Global ventricular function results from antagonistic forces generated by aggregated cardiomyocytes. Citation Format: • Burg MC, Lunkenheimer P, Niederer P et al. Pneumatic Distension of Ventricular Mural Architecture Validated Histologically. Fortschr Röntgenstr 2016; 188: 1045 - 1053.

Undetected Dural Leaks Complicated by Accidental Drainage of Cerebrospinal Fluid (CSF) can Lead to Severe Neurological Deficits.

PURPOSE: Intracranial hypotension has been reported as a complication of accidental drainage after surgical treatment in several cases. Application of negative pressure systems (wound drains, VAC(®)-therapy, chest tube drainage) had typically led to severe intracranial hypotension including intracranial hemorrhage and tonsillar herniation. In the last year the authors observed 2 cases of accidental spinal drainage of CSF in patients with neurological deficits, regressing after reduction of the device suction. MATERIAL AND METHODS: We conducted a systematic PubMed-based research of the literature to study the variety and frequency of the reported symptoms from 1st of January 1980 until 1st of October 2015. RESULTS: Reviewing the literature 24 relevant citations including 27 reported cases of posttraumatic or postoperative loss of CSF leading to neurological symptoms were identified. All 15 reported cases in which a negative pressure suction device had been applied showed severe neurological and radiological symptoms such as coma or brain herniation and intracranial hemorrhage. In all cases patients recovered rapidly after removal of the suction device. Milder symptoms were observed in the patients without negative pressure suction, mainly only presenting with headaches or cranial nerve involvement.Additionally, we give an overview about current recommendations regarding cranial and spinal imaging to rule out dural laceration and cranial hypotension. CONCLUSION: Patients with dural laceration complicated by accidental drainage of CSF can present with life-threatening conditions. Increasing use of negative pressure suction devices makes the reported condition an important differential diagnosis. A precise radiological examination can help to rule out dural laceration and intracranial hypotension. KEY POINTS: • Undetected dural laceration complicated by negative pressure suction drains can induce life-threatening symptoms.• Increasing use of negative pressure suction devices makes the reported condition an important differential diagnosis for radiologists Citation Format: • Sporns PB, Schwindt W, Cnyrim CD et al. Undetected Dural Leaks Complicated by Accidental Drainage of Cerebrospinal Fluid (CSF) can Lead to Severe Neurological Deficits. Fortschr Röntgenstr 2016; 188: 451 - 458.

Reduction of Advanced Breast Cancer Stages at Subsequent Participation in Mammography Screening.

PURPOSE: The decline in advanced breast cancer stages is presumably the most relevant surrogate parameter in mammography screening. It represents the last step in the causal cascade that is expected to affect breast cancer-related mortality. To assess the effectiveness of population-based screening, we analyzed the 2-year incidence rates of advanced breast cancers between women participating in the initial and in the first subsequent round. MATERIALS AND METHODS: The study included data from 19,563 initial and 18,034 subsequent examinations of one digital screening unit (2008 - 2010). Data on tumor stages, detected by screening or within the following interval of two years (2-year incidence), were provided by the epidemiological cancer registry. Rates of all and combined UICC stages 2, 3 and 4 (advanced stages) were reported for a two-year period. Proportions were tested for significance by using chi-square tests (p < 0.001). RESULTS: The 2-year incidence rate of all stages was significantly lower in participants in subsequent screening than in initial screening (0.85 vs. 1.29 per 100 women (%); p < 0.0001). A significantly lower 2-year incidence of advanced stages was observed for subsequent screening compared to initial screening (0.26 % vs. 0.48 %; p = 0.0007). Among women aged 50 to 59 years, the incidence of advanced stages was less clearly different (0.21 % vs. 0.35 %; p = 0.07) than in women aged 60 to 69 years (0.31 % vs. 0.70 %; p = 0.0008). CONCLUSION: During the change from prevalent to incident phase mammography screening, a program impact is seen by a lower 2-year incidence of advanced breast cancers within subsequent compared to initial participants, predominately in women aged 60 to 69 years. KEY POINTS: • The incidence of advanced tumor stages represents the most relevant surrogate parameter for screening effectiveness. • For the first time the 2-year incidence of advanced breast cancer stages after subsequent mammography screening was analyzed. • We observed a significant effect of screening on the 2-year incidence of advanced stages, predominately in the age group 60 to 69 years.

Selective arterial Embolisation of Aneurysmal Bone Cysts of the Sacrum: a promising Alternative to Surgery.

PURPOSE: The sacrum is a rare but unfavourable location for Aneurysmal Bone Cysts (ABCs), surgical procedures aiming to achieve local tumour control can be mutilating. Aim of this study was to evaluate whether selective arterial embolisation (AE) of ABC of the sacrum is an effective treatment and might be an alternative to surgical treatment options. MATERIALS AND METHODS: Between 2007 and 2011 six patients (mean age 13.7 years, range 8 - 18 years) with an ABC of the sacrum were treated by AE. Follow-up was performed by MRI-scans as well as clinical examination (mean 36.5 months, range 14 - 56 months). RESULTS: No treatment related complications have been observed. AE resulted in devascularisation of ABC and led to local tumour control in all patients. A partial consolidation was noticed in three patients. Pain relief was achieved in five of six patients, neurological deficits dissolved. In two patients more than one embolization was necessary. In one of these patients due to exacerbation of pain a surgical decompression was performed. CONCLUSION: AE of sacral ABCs can serve as an effective and safe treatment option. Thus it might be an alternative to potentially harmful surgical procedures. In case of ongoing tumour growth or pain recurrence AE can be repeated. In case of treatment failure surgical interventions are still possible. KEY POINTS: • transarterial embolisation enables local tumour control in sacral ABCs. • transarterial embolisation of sacral ABCs is a safe procedure. • in case of tumour progression repetitive embolisations are possible and effective.