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Zusammenfassung  Verletzungen des Kniegelenkes sind häufig. Die „Ottawa knee rules“ bieten eine Entscheidungshilfe, ob Röntgenaufnahmen indiziert sind. Mittels Sonographie können Verletzungen der Streckapparates und des vorderen Kreuzbandes erkannt werden. Ebenso gelingt der Nachweis eines Lipohämarthros als indirektem Zeichen einer intraartikulären Fraktur. Bei komplexen Frakturen, z. B. Tibiaplateaufrakturen, ist eine weiterführende Diagnostik mittels CT (Computertomographie) zur Klassifizierung und präoperativen Planung notwendig. Die Multislice-CT mit gleichzeitiger CT-Angiographie ermöglicht die Anfertigung dreidimensionaler Rekonstruktionen und die Möglichkeit der nichtinvasiven Gefäßdarstellung. Die MRT (Magnetresonanztomographie) ist der Goldstandard zum Nachweis okkulter Frakturen und Verletzungen an Bändern und Menisken. Bei höheren Feldstärken verbessert sich die Diagnostik von Knorpelläsionen. Die virtuelle MR-Arthrographie ist insbesondere nach Meniskusoperation und bei Knorpelläsionen der konventionellen MRT überlegen. [ABSTRACT FROM AUTHOR]

Objective: Whole-body MRI (wb-MRI) is increasingly used in research and screening but little is known about the effects of incidental findings (IFs) on health service utilisation and costs. Such effects are particularly critical in an observational study. Our principal research question was therefore how participation in a wb-MRI examination with its resemblance to a population-based health screening is associated with outpatient service costs., Design: Prospective cohort study., Setting: General population Mecklenburg-Vorpommern, Germany., Participants: Analyses included 5019 participants of the Study of Health in Pomerania with statutory health insurance data. 2969 took part in a wb-MRI examination in addition to a clinical examination programme that was administered to all participants. MRI non-participants served as a quasi-experimental control group with propensity score weighting to account for baseline differences., Primary and Secondary Outcome Measures: Outpatient costs (total healthcare usage, primary care, specialist care, laboratory tests, imaging) during 24 months after the examination were retrieved from claims data. Two-part models were used to compute treatment effects., Results: In total, 1366 potentially relevant IFs were disclosed to 948 MRI participants (32% of all participants); most concerned masses and lesions (769 participants, 81%). Costs for outpatient care during the 2-year observation period amounted to an average of €2547 (95% CI 2424 to 2671) for MRI non-participants and to €2839 (95% CI 2741 to 2936) for MRI participants, indicating an increase of €295 (95% CI 134 to 456) per participant which corresponds to 11.6% (95% CI 5.2% to 17.9%). The cost increase was sustained rather than being a short-term spike. Imaging and specialist care related costs were the main contributors to the increase in costs., Conclusions: Communicated findings from population-based wb-MRI substantially impacted health service utilisation and costs. This introduced bias into the natural course of healthcare utilisation and should be taken care for in any longitudinal analyses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The Study of Health in Pomerania (SHIP), a population-based study from a rural state in northeastern Germany with a relatively poor life expectancy, supplemented its comprehensive examination program in 2008 with whole-body MR imaging at 1.5 T (SHIP-MR). We reviewed more than 100 publications that used the SHIP-MR data and analyzed which sequences already produced fruitful scientific outputs and which manuscripts have been referenced frequently. Upon reviewing the publications about imaging sequences, those that used T1-weighted structured imaging of the brain and a gradient-echo sequence for R2* mapping obtained the highest scientific output; regarding specific body parts examined, most scientific publications focused on MR sequences involving the brain and the (upper) abdomen. We conclude that population-based MR imaging in cohort studies should define more precise goals when allocating imaging time. In addition, quality control measures might include recording the number and impact of published work, preferably on a bi-annual basis and starting 2 years after initiation of the study. Structured teaching courses may enhance the desired output in areas that appear underrepresented.

Background: Self-reports of medical findings are indispensable in clinical practice and research but subject to recall bias. We analysed the recall accuracy of notifications about incidental findings (IFs) from a whole-body MRI examination and assessed determinants of recall error., Methods: Data from 3746 participants of a postal follow-up survey conducted on average 2.47 years after examination in the population-based Study of Health in Pomerania were analysed. Among those, 2185 (58.3%) underwent whole-body MRI at baseline, and findings of potential clinical relevance were disclosed in standardised postal letters. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated to determine the accuracy of self-reports. Poisson regression analysis was conducted to analyse predictors for false-positive and false-negative recall., Results: An IF was disclosed to 622 (28.5%) individuals; 81.5% had tumour relevance. The overall sensitivity and PPV of participants' self-reports were 80% and 60%, respectively. PPvs were higher among women, better educated and married participants and among those with good verbal memory. Among MRI participants, lower educational level was associated with a higher risk of false-positive recall (risk ratio (RR) 1.44, 95% CI 1.01 to 2.03), while increasing age was associated with a higher risk of false-negative recall (RR 1.64, 95% CI 1.33 to 2.01)., Conclusions: Most participants correctly recalled disclosed IFs. However, the probability of an event in case of a positive recall is barely above 50%. Therefore, relying on subjects' recall of disclosed IFs will lead to a relevant proportion of errors. Clinicians and researchers should be aware of this problem and of participants' characteristics which may moderate the probability of correct decisions based on recalled findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: The study aimed at investigating the correlation between ductoscopic and histopathological findings and clarify whether the former allow for accurate prediction of malignancy., Patients and Methods: The prospective national multi-center study covered a sample of 224 patients with pathologic nipple discharge. A total of 214 patients underwent ductoscopy with subsequent extirpation of the mammary duct. The ductoscopic findings were categorized according to shape, number, color and surface structure of lesions and vascularity and compared to the histological results and analyses., Results: Ductoscopy revealed lesions in 134 of 214 patients (62.2%). The criteria "multiple versus solitary lesion" differed significantly between malignant and benign lesions. All other criteria were not statistically significant. Malignant tumors were more frequently presented as multiple lesions, benign lesions or masses as solitary lesions (80% vs. 24.8%; p=0.018)., Conclusion: The ductoscopic criterion "solitary vs. multiple lesion" appears to have a low diagnostic prediction of malignancy or benignity., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Purpose: The main purpose of this work is to develop, apply, and evaluate an efficient approach for breast density estimation in magnetic resonance imaging data, which contain strong artifacts including intensity inhomogeneities., Methods: We present a pipeline for breast density estimation, which consists of intensity inhomogeneity correction, breast volume segmentation, nipple extraction, and fibroglandular tissue segmentation. For the segmentation steps, a well-known deep learning architecture is employed., Results: The average Dice coefficient for the breast parenchyma is [Formula: see text], which outperforms the classical state-of-the-art approach by a margin of [Formula: see text]., Conclusion: The proposed solution is accurate and highly efficient and has potential to be applied for big epidemiological data with thousands of participants.

Purpose: To provide population-based reference values for cervical spinal canal parameters and vertebral body (VB) width and to study their associations with sex, age, body height, body weight and body mass index (BMI) using MRI., Methods: Cross-sectional analyses included data from 2,453 participants, aged 21-89 years, of the population-based Study of Health in Pomerania (SHIP) who underwent whole-body MRI at 1.5 Tesla between July 2008 and March 2011. A standardised reading was performed for the C2-C7 cervical spine levels at sagittal T2 TSE weighted sequences., Results: Reference intervals for spinal canal parameters were similar in males and females, while VB width was on average 2.1-2.2 mm larger in males. Age effects were only substantial regarding VB width with a 0.5 mm per ten-year age increase. Body height effects were only substantial regarding the osseous spinal canal and VB width. Body weight and BMI effects are mostly not substantial., Conclusions: Our study provides MRI-based reference values for the cervical spinal canal parameters in an adult Caucasian population. Except for VB width, associations with sex, age and somatometric measures are mostly small and thus have only limited clinical implications. Some available cut-off values may need a revision because they likely overestimate risks., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: This study was supported by the commercial funder Siemens Healthcare. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Observational studies and intervention trials suggest that physical activity (PA) is beneficial for human brain morphology, especially in older individuals. Few population-based studies examined whether domain-specific PA is associated with brain volumes. Accordingly, we studied putative associations of PA during leisure time, sports and work with volumes of the hippocampus, the prefrontal cortex, the temporal lobe, gray matter (GM), white matter (WM) and total brain (TBV) after 5.9 years by applying volumetric analysis and voxel-based morphometry (VBM) with SPM 8/VBM 8 to brain magnetic resonance imaging data of 834 participants (447 women) aged 25 to 83 years from the population-based Study of Health in Pomerania. The Baecke questionnaire was used to assess domain-specific PA (Leisure time, Sport, and Work Index) at baseline. After correcting for multiple testing, volumetric analyses did not show any significant association of domain-specific PA and volumes of the hippocampus, the prefrontal cortex, the temporal lobe, GM, WM and TBV. Multivariable-adjusted VBM analyses of the associations between PA domains with GM and WM volumes did not reveal any statistically significant results. Region of interest analyses revealed a statistically significant cluster of increased GM volume in the bilateral anterior cingulate cortex in association with PA during sports. In conclusion, the overall results contrast with the findings from previous studies that found significant associations between PA and brain volumes. In addition, it remains unclear whether a differential association exists between domains of PA and brain volumes. Thus, future studies with larger sample size and prospective design are needed to investigate potential domain-specific associations of PA with brain volumes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10 -3 ) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Abdominal obesity is a major driver for adverse medical conditions. While an interaction between adipose tissue and thyroid function is thought to exist, to our knowledge, no study has examined the effect of thyroid-stimulating hormone (TSH) on visceral adipose tissue (VAT) in a population-based context., Objective: We determined an association between serum TSH levels and VAT., Methods: A sample of 1,021 female and 956 male adults aged 20-79 years was drawn from registry offices in the cross-sectional, population-based Study of Health in Pomerania Trend (SHIP Trend) in Northeast Germany from 2008 to 2012. Our main exposure was serum TSH levels. Our main outcome was VAT measured using magnetic resonance imaging. The possibly mediating role of leptin on the TSH-VAT association was also assessed., Results: A total of 1,719 participants (87.9%) had serum TSH levels within the reference range. The mean volume of VAT was 5.33 liters for men and 2.83 liters for women. No association between TSH and VAT (β = 0.06, 95% CI: -0.02, 0.14) was observed, and there were no differences detected between sexes. VAT was strongly associated with leptin with a greater effect in women than in men. Leptin was strongly associated with TSH., Conclusions: No association between TSH and VAT was observed. Other biomarkers such as leptin may play a role in the relationship between thyroid function and metabolic risk.

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r g =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.

Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρ genetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

The clinical relevance of scaphoid bone fractures is reflected by their high incidence, accounting for approximately 60 % among carpal fractures and for 2-3 % of all fractures. With adequate therapy most scaphoid bone fractures heal completely without complications. Insufficient immobilization or undiagnosed fractures increase the risk of nonunion and the development of pseudarthrosis.X-ray examination enables initial diagnosis of scaphoid fracture in 70-80 % of cases. Positive clinical symptoms by negative x‑ray results require further diagnostics by multi-slice spiral CT (MSCT) or MRI to exclude or confirm a fracture. In addition to the diagnosis and description of fractures MSCT is helpful for determining the stage of nonunion. Contrast enhanced MRI is the best method to assess the vitality of scaphoid fragments.

Background and Purpose: The presence of the apolipoprotein E ε4 allele is the strongest sporadic Alzheimer disease genetic risk factor. We hypothesized that apolipoprotein E ε4 carriers and noncarriers may already differ in imaging patterns in midlife. We therefore sought to identify the effect of apolipoprotein E genotype on brain atrophy across almost the entire adult age span by using advanced MR imaging-based pattern analysis., Materials and Methods: We analyzed MR imaging scans of 1472 participants from the Study of Health in Pomerania (22-90 years of age). We studied the association among age, apolipoprotein E ε4 carrier status, and brain atrophy, which was quantified by using 2 MR imaging-based indices: Spatial Pattern of Atrophy for Recognition of Brain Aging (summarizing age-related brain atrophy) and Spatial Pattern of Abnormality for Recognition of Early Alzheimer Disease (summarizing Alzheimer disease-like brain atrophy patterns), as well as the gray matter volumes in several Alzheimer disease- and apolipoprotein E-related ROIs (lateral frontal, lateral temporal, medial frontal, and hippocampus)., Results: No significant association was found between apolipoprotein E ε4 carrier status and the studied ROIs or the MR imaging-based indices in linear regression models adjusted for age, sex, and education, including an interaction term between apolipoprotein E and age., Conclusions: Our study indicates that measurable apolipoprotein E-related brain atrophy does not occur in early adulthood and midlife and suggests that such atrophy may only occur more proximal to the onset of clinical symptoms of dementia., Competing Interests: The authors declare no competing interests, (© 2016 by American Journal of Neuroradiology.)

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20-90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q<0.001). ABA patterns of atrophy were partially overlapping with, but notably deviating from those typically found in AD. Subjects with ABA had higher SPARE-AD values; largely due to the partial spatial overlap of associated patterns in temporal regions. The AD polygenic risk score was significantly associated with SPARE-AD but not with SPARE-BA. Our findings suggest that ABA is likely characterized by pathophysiologic mechanisms that are distinct from, or only partially overlapping with those of AD.

White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE-AD variance. Multivariable regression showed significant relationship between white matter hyperintensities volume and hypertension (P = 0.001), diabetes mellitus (P = 0.023), smoking (P = 0.002) and education level (P = 0.003). The only significant association with cognitive tests was with the immediate recall of the California verbal and learning memory test. No significant association was present with the APOE genotype. These results support the hypothesis that white matter hyperintensities contribute to patterns of brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer's disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: To generate reference values for thoracic and abdominal aortic diameters determined by magnetic resonance imaging (MRI) and analyse their association with cardiovascular risk factors in the general population., Methods: Data from participants (n = 1759) of the Study of Health in Pomerania were used for analysis in this study. MRI measurement of thoracic and abdominal aortic diameters was performed. Parameters for calculation of reference values according to age and sex analysis were provided. Multivariable linear regression models were used for determination of aortic diameter-related risk factors, including smoking, blood pressure (BP), high-density lipoprotein cholesterol (HDL-C)., Results: For the ascending aorta (β = -0.049, p < 0.001), the aortic arch (β = -0.061, p < 0.001) and the subphrenic aorta (β = -0.018, p = 0.004), the body surface area (BSA)-adjusted diameters were lower in men. Multivariable-adjusted models revealed significant increases in BSA-adjusted diameters with age for all six aortic segments (p < 0.001). Consistent results for all segments were observed for the positive associations of diastolic BP (β = 0.001; 0.004) and HDL (β = 0.035; 0.087) with BSA-adjusted aortic diameters and for an inverse association of systolic BP (β = -0.001)., Conclusions: Some BSA-adjusted median aortic diameters are smaller in men than in women. All diameters increase with age, diastolic blood pressure and HDL-C and decrease as systolic BP increases., Key Points: • Median aortic diameter increases with age and diastolic blood pressure. • Median aortic diameter is larger in men than in women. • Some BSA-adjusted median aortic diameters are smaller in men than in women.

Objective: The FKBP5 gene codes for a co-chaperone that regulates glucocorticoid receptor sensitivity and thereby impacts the reactivity of the hypothalamic-pituitary-adrenal (HPA)-axis. Evidence suggested that subjects exposed to childhood abuse and carrying the TT genotype of the FKBP5 gene single nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to stress-related disorders., Method: The hypothesis that abused TT genotype carriers show changes in gray matter (GM) volumes in affect-processing brain areas was investigated. About 1,826 Caucasian subjects (age ≤ 65 years) from the general population [Study of Health in Pomerania (SHIP)] in Germany were investigated. The interaction between rs1360780 and child abuse (Childhood Trauma Questionnaire) and its effect on GM were analyzed., Results: Voxel-based whole-brain interaction analysis revealed three large clusters (FWE-corrected) of reduced GM volumes comprising the bilateral insula, the superior and middle temporal gyrus, the bilateral hippocampus, the right amygdala, and the bilateral anterior cingulate cortex in abused TT carriers. These results were not confounded by major depressive disorders. In region of interest analyses, highly significant volume reductions in the right hippocampus/parahippocampus, the bilateral anterior and middle cingulate cortex, the insula, and the amygdala were confirmed in abused TT carriers compared with abused CT/CC carriers., Conclusion: The results supported the hypothesis that the FKBP5 rs1360780 TT genotype predisposes subjects who have experienced childhood abuse to widespread structural brain changes in the subcortical and cortical emotion-processing brain areas. Those brain changes might contribute to an increased vulnerability of stress-related disorders in TT genotype carriers., (© 2016 Wiley Periodicals, Inc.)

Intensity inhomogeneity (bias field) is a common artefact in magnetic resonance (MR) images, which hinders successful automatic segmentation. In this work, a novel algorithm for simultaneous segmentation and bias field correction is presented. The proposed energy functional allows for explicit regularization of the bias field term, making the model more flexible, which is crucial in presence of strong inhomogeneities. An efficient minimization procedure, attempting to find the global minimum, is applied to the energy functional. The algorithm is evaluated qualitatively and quantitatively using a synthetic example and real MR images of different organs. Comparisons with several state-of-the-art methods demonstrate the superior performance of the proposed technique. Desirable results are obtained even for images with strong and complicated inhomogeneity fields and sparse tissue structures., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Unlabelled: Chronic back pain (CBP) is associated with circumscribed atrophy in gray matter (GM) predominantly localized in areas of the so-called pain matrix and the prefrontal cortex (PFC). Previous studies applying voxel-based morphometry (VBM) for identifying structural brain alterations related to CBP have reported inconsistent results, were limited to small sample sizes, and often did not control for medication. We therefore used VBM for high-resolution magnetic resonance images to investigate the association of CBP and regional GM volume in 111 individuals with CBP and 432 pain-free controls derived from the representative Study of Health in Pomerania, controlling for effects of medication. CBP was associated with decreased regional GM in the ventrolateral PFC and dorsolateral PFC, both the ventral and dorsal medial PFC, and the anterior insula. Pain intensity showed a weak negative correlation with GM volume in the left dorsolateral PFC, ventrolateral PFC, and anterior cingulate cortex. The CBP sample showed alterations in regions commonly associated with pain processing and emotional demands. To our knowledge, this is the first VBM study reporting decreased regional GM volume in the medial PFC in a CBP sample. We were unable to confirm alterations in regions other than the dorsolateral PFC and the insula., Perspective: Previous studies reported inconsistent results for brain areas altered in chronic pain conditions, which may be in part attributable to small sample sizes, medication use, or emotional comorbidities. This study in a large and representative cohort helps to clarify these issues., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)

This study examined the long-term impact of whole-body MRI and the disclosure of incidental findings on quality of life (QoL) and depressive symptoms in a general population cohort. Analyses were conducted among 4420 participants of the Study of Health in Pomerania SHIP-Trend cohort, of which 2188 received a whole-body MRI examination. A 2.5-year postal follow-up of SHIP-Trend (response: 86%) included the Short Form Health Survey (SF-12), based on which the Mental Health Component Summary Score (MCS), and Physical Health Component Summary Score (PCS) were computed. The Patient Health Questionnaire (PHQ-9) was applied to assess depressive symptoms. Generalized estimation equation models were used to assess intervention effects, and statistical weights were applied to account for selective attrition. MRI participants had higher levels of education and employment than nonparticipants. Mean QoL indicators differed little at baseline between MRI participants and nonparticipants. Intervention effects per year on depression and QoL were negligible in (1) MRI participants versus nonparticipants [PCS: unstandardized β = -0.06 (95% CI -0.30 to 0.18);, Mcs: β = -0.01 (95% CI -0.29 to 0.29); PHQ-9: 0.08 (-0.03 to 0.18)], and (2) MRI participants with a disclosed incidental finding versus those without [PCS: β = -0.03 (-0.39 to 0.33);, Mcs: β = -0.26 (95% CI -0.65 to 0.13); PHQ-9: 0.03 (-0.10 to 0.15)]. The body site of the finding had only minor effects on the course of our studied outcomes. Whole-body MRI can be implemented in a population-based study without long-term effects on QoL indicators and depressive symptoms. This does not exclude the possibility of effects on more subtle psychosocial outcomes, such as health concerns or health behaviour, all of which require further attention.

Epidemiological studies comprise heterogeneous data about a subject group to define disease-specific risk factors. These data contain information (features) about a subject's lifestyle, medical status as well as medical image data. Statistical regression analysis is used to evaluate these features and to identify feature combinations indicating a disease (the target feature). We propose an analysis approach of epidemiological data sets by incorporating all features in an exhaustive regression-based analysis. This approach combines all independent features w.r.t. a target feature. It provides a visualization that reveals insights into the data by highlighting relationships. The 3D Regression Heat Map, a novel 3D visual encoding, acts as an overview of the whole data set. It shows all combinations of two to three independent features with a specific target disease. Slicing through the 3D Regression Heat Map allows for the detailed analysis of the underlying relationships. Expert knowledge about disease-specific hypotheses can be included into the analysis by adjusting the regression model formulas. Furthermore, the influences of features can be assessed using a difference view comparing different calculation results. We applied our 3D Regression Heat Map method to a hepatic steatosis data set to reproduce results from a data mining-driven analysis. A qualitative analysis was conducted on a breast density data set. We were able to derive new hypotheses about relations between breast density and breast lesions with breast cancer. With the 3D Regression Heat Map, we present a visual overview of epidemiological data that allows for the first time an interactive regression-based analysis of large feature sets with respect to a disease.

Background: Tension pneumothorax is one of the leading causes of preventable death in both military and civilian trauma patients. Needle decompression is recommended in trauma guidelines as an emergency procedure to relieve increased intrapleural pressure. The main reason for decompression failure is reported to be insufficient needle length in proportion to the chest wall thickness (CWT). So far, population-based epidemiologic data on CWT are missing. Therefore, it was the aim of this work to investigate the CWT in the second intercostal space, midclavicular line, based on magnetic resonance imaging data of a large population-based sample. The second aim of this study was to explore the potential risk of iatrogenic lesions caused by the proximity of the intended puncture track to the internal mammary artery., Methods: A total of 2,574 healthy volunteers (mean [SD] age, 53.3 [13.9] years; range, 21-89 years) from the population-based cohort Study of Health in Pomerania (SHIP) were enrolled. CWT and the distance from the intended puncture track to the internal mammary artery were investigated with the chest sequences of a standardized 1.5-T whole-body magnetic resonance imaging., Results: For all 5,148 measured sites in 2,574 volunteers, the mean (SD) CWT was 5.1 (1.4) cm. The mean body mass index was determined to be 27.7 kg/m. The CWT correlated significantly with body weight and body mass index. The internal mammary artery was located medial to the intended puncture site in all participants; the mean (SD) distance was 5.7 (0.7) cm on the right and 5.5 (0.7) cm on the left side., Conclusion: Based on the population-based epidemiologic data presented in this study, the use of a needle of 7 cm in length is recommended to decompress a tension pneumothorax in the second intercostal space in the midclavicular line, which might successfully decompress more than 90% of the participants in this study. When using this anterior approach at the anatomically correct puncture site, safety margin to the internal mammary artery is sufficient so that the risk of iatrogenic lesion of the internal mammary artery should be minimal., Level of Evidence: Therapeutic/care management study, level IV.

We analyzed the putative association between abdominal obesity (measured in waist circumference) and gray matter volume (Study of Health in Pomerania: SHIP-2, N=758) adjusted for age and gender by applying volumetric analysis and voxel-based morphometry (VBM) with VBM8 to brain magnetic resonance (MR) imaging. We sought replication in a second, independent population sample (SHIP-TREND, N=1586). In a combined analysis (SHIP-2 and SHIP-TREND) we investigated the impact of hypertension, type II diabetes and blood lipids on the association between waist circumference and gray matter. Volumetric analysis revealed a significant inverse association between waist circumference and gray matter volume. VBM in SHIP-2 indicated distinct inverse associations in the following structures for both hemispheres: frontal lobe, temporal lobes, pre- and postcentral gyrus, supplementary motor area, supramarginal gyrus, insula, cingulate gyrus, caudate nucleus, olfactory sulcus, para-/hippocampus, gyrus rectus, amygdala, globus pallidus, putamen, cerebellum, fusiform and lingual gyrus, (pre-) cuneus and thalamus. These areas were replicated in SHIP-TREND. More than 76% of the voxels with significant gray matter volume reduction in SHIP-2 were also distinct in TREND. These brain areas are involved in cognition, attention to interoceptive signals as satiety or reward and control food intake. Due to our cross-sectional design we cannot clarify the causal direction of the association. However, previous studies described an association between subjects with higher waist circumference and future cognitive decline suggesting a progressive brain alteration in obese subjects. Pathomechanisms may involve chronic inflammation, increased oxidative stress or cellular autophagy associated with obesity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To detail the rationale, design, and future perspective of implementing whole-body magnetic resonance (MR) imaging in the German National Cohort, a large multicentric population-based study., Materials and Methods: All institutional review boards approved the study, and informed consent is obtained before study enrollment. Participants are enrolled from a random sample of the general population at five dedicated imaging sites among 18 recruitment centers. MR imaging facilities are equipped with identical 3.0-T imager technology and use uniform MR protocols. Imager-specific hardware and software settings remained constant over the study period. On-site and centralized measures of image quality enable monitoring of completeness of the acquisitions and quality of each of the MR sequences. Certified radiologists read all MR imaging studies for presence of incidental findings according to predefined algorithms., Results: Over a 4-year period, six participants per day are examined at each center, totaling a final imaging cohort of approximately 30 000 participants. The MR imaging protocol is identical for each site and comprises a set of 12 native series to cover neurologic, cardiovascular, thoracoabdominal, and musculoskeletal imaging phenotypes totaling approximately 1 hour of imaging time. A dedicated analysis platform as part of a central imaging core incorporates a thin client-based integrative and modular data handling platform to enable multicentric off-site image reading for incidental findings. Scientific analysis will be pursued on a per-project hypothesis-driven basis., Conclusion: Population-based whole-body MR imaging as part of the German National Cohort will serve to compile a comprehensive image repository, will provide insight into physiologic variants and subclinical disease burden, and has the potential to enable identification of novel imaging biomarkers of risk., ((©) RSNA, 2015 Online supplemental material is available for this article.)

Purpose: To determine the relationship between pancreatic fat content and type 2 diabetes and prediabetes., Materials and Methods: From the prospective population-based Study of Health in Pomerania (SHIP), 1367 volunteers (563 men, 678 women; median age, 50 years) underwent whole-body magnetic resonance (MR) imaging at 1.5 T, which included multiecho chemical shift-encoded acquisition of the abdomen. SHIP was approved by the institutional review board, and written informed consent was obtained from all participants. The proton density fat fraction (PDFF) was calculated after correction for T1 bias, T2* bias, multipeak spectral complexity of fat, and noise bias. On the basis of oral glucose tolerance test results, participants were grouped into those with normal glucose tolerance (n = 740), those with prediabetes (n = 431), and those with confirmed type 2 diabetes but without medication (n = 70). PDFF was assessed in the pancreatic head, body, and tail. Multivariable regression analysis was conducted to investigate possible relationships of PDFF with demographic factors, behavioral factors, and laboratory data associated with the metabolic syndrome., Results: In all subjects, the mean unadjusted pancreatic fat content was 4.4% (head, 4.6%; body, 4.9%; tail, 3.9%; being unequally distributed, P < .001). There was no significant difference in pancreatic PDFF among subjects with normal glucose tolerance, prediabetes, and type 2 diabetes (P = .980). Pancreatic PDFF showed a positive association with age and body mass index and a negative association with serum lipase activity (P < .001)., Conclusion: The presence of pancreatic fat is not related to prediabetes or diabetes, which suggests that it has little clinical relevance for an individual's glycemic status.

Background: Body mass index (BMI) and serum 25-hydroxy vitamin D3 (25OHD) concentrations are inversely related. As BMI contains only limited information regarding body fat distribution, we aimed to analyze the cross-sectional associations of abdominal visceral or subcutaneous adipose tissue, next to common adiposity measures, with the 25OHD concentration., Methods: Data were obtained from three cohorts of two large epidemiological studies in the northeast of Germany (Study of Health in Pomerania, SHIP-1 and SHIP-Trend), and in Denmark (Health2006). The study populations included adult men and women from the general population (N = 3072 SHIP-1, N = 803 SHIP-Trend, N = 3195 Health2006). Visceral and subcutaneous adipose tissue were quantified by magnetic resonance imagining (SHIP-Trend) or ultrasound (Health2006). Common adiposity measures, including BMI, waist circumference, waist-to-hip ratio, waist-to-height ratio, body surface area, and body fat percentage were determined by standardized methods in SHIP-1 and Health2006., Results: The average study participant was overweight (median BMI 27.4, 26.6, and 25.2 kg/m(2) in SHIP-1, SHIP-Trend, and Health2006, respectively). Visceral and subcutaneous adipose tissue as well as the common adiposity measures were inversely associated with serum 25OHD concentrations in linear regression models adjusted for age, sex, alcohol consumption, physical activity, smoking status, and month of blood sampling., Conclusions: Next to common adiposity measures, also abdominal visceral or subcutaneous adipose tissue are inversely associated with serum 25OHD concentrations in the general adult population.

The neuropeptide neurokinin 3 (NK3) and its receptor modulate cholinergic activity of the basal forebrain (BF) and are implicated in learning and memory. In Alzheimer's disease, the rs2765 single-nucleotide polymorphism (SNP) of the NK3 receptor-coding gene TACR3 was correlated with the right hippocampus volume. Here, we studied the association of the rs2765 SNP with magnetic resonance imaging-based volumes of the BF and hippocampus in a population-based sample of 1967 participants between 21 and 90 years of age. The rs2765 SNP was significantly associated with the most anterior BF volume corresponding to the medial septum/diagonal band, and with a significantly steeper age-related volume decline. The rs2765 SNP was not associated with other BF subvolumes or hippocampus volumes. Apolipoprotein E ε4 showed no correlation with any brain volume or global cognition. Our findings in a large population-based sample suggest an association of an NK3 receptor SNP with age-related decline of rostral cholinergic BF volume., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the association of cardiovascular risk factors with wall thickness of the ascending and descending thoracic aorta in the general population., Materials and Methods: The study included 1,176 individuals (523 women) 21-83 years old from the Study of Health in Pomerania without history of stroke or myocardial infarction. Aortic wall thickness (AWT) was determined by cine magnetic resonance imaging. The associations of AWT with the cardiovascular risk factors male sex, age, smoking, body mass index (BMI), systolic and diastolic blood pressure, hemoglobin A1c, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were assessed by multivariable linear regression models, and interaction effects were tested., Results: Male sex (β = .086, P < .001), age (β = .006, P < .001), and BMI (β = .013, P < .001) were positively associated with the AWT of the ascending aorta. Male sex (β = .105, P < .001), age (β = .006, P < .001), current smoker (β = .044, P = .010), BMI (β = .013, P < .001), and HDL-C (β = .057, P = .008) revealed a positive association with AWT of the descending aorta. LDL-C (β = -.024, P = .009; β = -.018, P = .010) was inversely associated with the AWT of the ascending and descending aorta, respectively. Triglyceride levels (β = .024, P = .027; β = .018, P = .024) showed a positive association with the AWT of the ascending and descending aorta, respectively, in men, but not in women., Conclusions: Established cardiovascular risk factors, including male sex, older age, smoking, high BMI, and high triglyceride levels, were associated with increasing thoracic AWT of the ascending and descending aorta. High HDL-C and low LDL-C levels were correlated with AWT., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Clinical/methodical Issue: Fatty liver disease plays an important role in the development of type 2 diabetes. Accurate techniques for detection and quantification of liver fat are essential for clinical diagnostics., Standard Radiological Methods: Chemical shift-encoded magnetic resonance imaging (MRI) is a simple approach to quantify liver fat content., Methodical Innovations: Liver fat quantification using chemical shift-encoded MRI is influenced by several bias factors, such as T2* decay, T1 recovery and the multispectral complexity of fat., Performance: The confounder corrected proton density fat fraction is a simple approach to quantify liver fat with comparable results independent of the software and hardware used., Achievements: The proton density fat fraction is an accurate biomarker for assessment of liver fat., Practical Recommendations: An accurate and reproducible quantification of liver fat using chemical shift-encoded MRI requires a calculation of the proton density fat fraction.

Background: The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies., Methods and Results: We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16)., Conclusions: We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms., (© 2015 American Heart Association, Inc.)

In two large genome-wide association studies, an intergenic single-nucleotide polymorphism (SNP; rs7294919) involved in TESC gene regulation has been associated with hippocampus volume. Further characterization of neurobiological effects of the TESC gene is warranted using multimodal brain-wide structural and functional imaging. Voxel-based morphometry (VBM8) was used in two large, well-characterized samples of healthy individuals of West-European ancestry (Münster sample, N=503; SHIP-TREND, N=721) to analyze associations between rs7294919 and local gray matter volume. In subsamples, white matter fiber structure was investigated using diffusion tensor imaging (DTI) and limbic responsiveness was measured by means of functional magnetic resonance imaging (fMRI) during facial emotion processing (N=220 and N=264, respectively). Furthermore, gene x environment (G × E) interaction and gene x gene interaction with SNPs from genes previously found to be associated with hippocampal size (FKBP5, Reelin, IL-6, TNF-α, BDNF and 5-HTTLPR/rs25531) were explored. We demonstrated highly significant effects of rs7294919 on hippocampal gray matter volumes in both samples. In whole-brain analyses, no other brain areas except the hippocampal formation and adjacent temporal structures were associated with rs7294919. There were no genotype effects on DTI and fMRI results, including functional connectivity measures. No G × E interaction with childhood maltreatment was found in both samples. However, an interaction between rs7294919 and rs2299403 in the Reelin gene was found that withstood correction for multiple comparisons. We conclude that rs7294919 exerts highly robust and regionally specific effects on hippocampal gray matter structures, but not on other neuropsychiatrically relevant imaging markers. The biological interaction between TESC and RELN pointing to a neurodevelopmental origin of the observed findings warrants further mechanistic investigations.

Snake bites are rare events in Germany and are not life-threatening with usually only mild clinical symptoms. The most widespread venomous snake is the common European adder (Vipera berus). Here we present the case of a 53-year-old woman who was bitten by a common adder. Although the patient was initially in stable condition she developed edematous swelling of the complete lower limb, subcutaneous bleeding, and rhabdomyolysis. The aim of this report is to raise awareness that even in a central European country like Germany snake bites with a life-threatening course can occur and need immediate attention and medical care.

The genetic determinants of cerebral asymmetries are unknown. Sex differences in asymmetry of the planum temporale (PT), that overlaps Wernicke's classical language area, have been inconsistently reported. Meta-analysis of previous studies has suggested that publication bias established this sex difference in the literature. Using probabilistic definitions of cortical regions we screened over the cerebral cortex for sexual dimorphisms of asymmetry in 2337 healthy subjects, and found the PT to show the strongest sex-linked asymmetry of all regions, which was supported by two further datasets, and also by analysis with the FreeSurfer package that performs automated parcellation of cerebral cortical regions. We performed a genome-wide association scan (GWAS) meta-analysis of PT asymmetry in a pooled sample of 3095 subjects, followed by a candidate-driven approach which measured a significant enrichment of association in genes of the 'steroid hormone receptor activity' and 'steroid metabolic process' pathways. Variants in the genes and pathways identified may affect the role of the PT in language cognition., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Epidemiological population studies impose information about a set of subjects (a cohort) to characterize disease-specific risk factors. Cohort studies comprise heterogenous variables describing the medical condition as well as demographic and lifestyle factors and, more recently, medical image data. We propose an Interactive Visual Analysis (IVA) approach that enables epidemiologists to rapidly investigate the entire data pool for hypothesis validation and generation. We incorporate image data, which involves shape-based object detection and the derivation of attributes describing the object shape. The concurrent investigation of image-based and non-image data is realized in a web-based multiple coordinated view system, comprising standard views from information visualization and epidemiological data representations such as pivot tables. The views are equipped with brushing facilities and augmented by 3D shape renderings of the segmented objects, e.g., each bar in a histogram is overlaid with a mean shape of the associated subgroup of the cohort. We integrate an overview visualization, clustering of variables and object shape for data-driven subgroup definition and statistical key figures for measuring the association between variables. We demonstrate the IVA approach by validating and generating hypotheses related to lower back pain as part of a qualitative evaluation.

Alexithymia is perceived as a personality construct involving deficits in the cognitive processing of emotion. Brain areas that process emotions might be structurally altered in affected people. Subjects from the Study of Health in Pomerania who underwent whole body magnetic resonance imaging were investigated. After quality control procedures 2,589 subjects with Toronto Alexithymia Scale 20 (TAS-20) data and interview-based information on major depressive disorder (MDD) were available. After exclusion of study participants who were older than 65 years or had MDD in their lifetime, 1,685 subjects were included in the voxel-based morphometric (VBM 8) analyses. In whole-brain analyses, the TAS-20 total score was associated with less gray matter (GM) volumes of the bilateral dorsal anterior cingulate cortex (dACC). The TAS-20 factor scale difficulty identifying feelings (DIF) was associated with less GM volume in three clusters: dACC, left middle and inferior temporal gyrus, left fusiform gyrus and cerebellum. The lower GM volume in the left fusiform gyrus was specific for females. Absolute GM volume analyses also revealed associations between the factor scales difficulty describing feelings, external orientated thinking and the dACC. Adjustment for current symptoms of anxiety and depression did not change the effects sizes substantially. In conclusion, lower GM volume in the dACC represents the major structural correlate of alexithymia. Associations with DIF suggest a prominent involvement of left temporal areas. These areas represent language and semantic processing and might be involved in the cognitive processing of emotions and the conscious identification of feelings., (© 2014 Wiley Periodicals, Inc.)

Breast density is a risk factor associated with the development of breast cancer. Usually, breast density is assessed on two dimensional (2D) mammograms using the American College of Radiology (ACR) classification. Magnetic resonance imaging (MRI) is a non-radiation based examination method, which offers a three dimensional (3D) alternative to classical 2D mammograms. We propose a new framework for automated breast density calculation on MRI data. Our framework consists of three steps. First, a recently developed method for simultaneous intensity inhomogeneity correction and breast tissue and parenchyma segmentation is applied. Second, the obtained breast component is extracted, and the breast-air and breast-body boundaries are refined. Finally, the fibroglandular/parenchymal tissue volume is extracted from the breast volume. The framework was tested on 37 randomly selected MR mammographies. All images were acquired on a 1.5T MR scanner using an axial, T1-weighted time-resolved angiography with stochastic trajectories sequence. The results were compared to manually obtained groundtruth. Dice's Similarity Coefficient (DSC) as well as Bland-Altman plots were used as the main tools for evaluation of similarity between automatic and manual segmentations. The average Dice's Similarity Coefficient values were 0.96±0.0172 and 0.83±0.0636 for breast and parenchymal volumes, respectively. Bland-Altman plots showed the mean bias (%) ± standard deviation equal 5.36±3.9 for breast volumes and -6.9±13.14 for parenchyma volumes. The automated framework produced sufficient results and has the potential to be applied for the analysis of breast volume and breast density of numerous data in clinical and research settings.

The hippocampus--crucial for memory formation, recall and mood regulation--is involved in the pathophysiology of dementia and depressive disorders. Recent genome-wide association studies (GWAS) have identified five genetic loci associated with hippocampal volume (HV). Previous studies have described psychosocial and clinical factors (for example, smoking, type 2 diabetes and hypertension) to have an impact on HV. However, the interplay between genetic, psychosocial and clinical factors on the HV remains unclear. Still, it is likely that genetic variants and clinical or psychosocial factors jointly act in modifying HV; it might be possible they even interact. Knowledge of these factors might help to quantify ones individual risk of or rather resilience against HV loss. We investigated subjects (N=2463; 55.7% women; mean age 53 years) from the Study of Health in Pomerania (SHIP-2; SHIP-TREND-0) who underwent whole-body magnetic resonance imaging (MRI) and genotyping. HVs were estimated with FreeSurfer. For optimal nonlinear model fitting, we used regression analyses with restricted cubic splines. Genetic variants and associated psychosocial or clinical factors were jointly assessed for potential two-way interactions. We observed associations between HV and gender (P<0.0001), age (P<0.0001), body height (P<0.0001), education (P=0.0053), smoking (P=0.0058), diastolic blood pressure (P=0.0211), rs7294919 (P=0.0065), rs17178006 (P=0.0002), rs6581612 (P=0.0036), rs6741949 (P=0.0112) and rs7852872 (P=0.0451). In addition, we found three significant interactions: between rs7294919 and smoking (P=0.0473), rs7294919 and diastolic blood pressure (P=0.0447) and between rs7852872 and rs6581612 (P=0.0114). We suggest that these factors might have a role in the individual susceptibility to hippocampus-associated disorders.

Nicotine modulates prefrontal processing when tested with functional imaging. Previous studies on changes in regional brain volumes in small samples, reporting different life-time exposure to nicotine, identified reduced volume in smokers in prefrontal areas but reported controversial results for other areas. We investigated the association of cigarette smoking and regional gray and white matter volume by using voxel-based morphometry (VBM) for T1-weighted high-resolution magnetic resonance imaging in 315 current-smokers and 659 never-smokers from the representative Study of Health in Pomerania (SHIP). Our study showed that in current-smokers smoking is significantly associated with gray matter volume loss in the prefrontal cortex, the anterior cingulate cortex, the insula, and the olfactory gyrus. White matter volumes were not relevantly reduced in current-smokers. In current-smokers, we found associations of gray matter loss and smoking exposure (pack-years) in the prefrontal cortex, the anterior and middle cingulate cortex, and the superior temporal and angular gyrus, which however did not stand corrections for multiple testing. We confirmed associations between smoking and gray matter differences in the prefrontal cortex, the anterior cingulate cortex and the insula in the general population of Pomerania (Germany). For the first time, we identified differences in brain volumes in the olfactory gyrus. Other cerebral regions did not show significant differences when correcting for multiple comparisons within the whole brain. The regions of structural deficits might be involved in addictive behavior and withdrawal symptoms, whereas further investigations have to show if the observed atrophies were caused by smoking itself or are preexisting differences between smoking and non-smoking individuals.

Objectives: To provide age- and sex-specific reference values for MRI-derived wall thickness of the ascending and descending aorta in the general population., Materials and Methods: Data of 753 subjects (311 females) aged 21-81 years were analysed. MRI was used to determine the aortic wall thickness (AWT). Equations for reference value calculation according to age were established for females and males., Results: Median wall thickness of the ascending aorta was 1.46 mm (5th-95th range: 1.15-1.88 mm) for females and 1.56 mm (1.22-1.99 mm) for males. Median wall thickness of the descending aorta was 1.26 mm (0.97-1.58 mm) in females and 1.36 mm (1.04-1.75 mm) in males. While median and 5th and 95th percentiles for the ascending and descending aorta increased with age in both sexes, the association between age and median AWT was stronger in males than in females for both the ascending and descending aorta., Conclusions: Reference values for the ascending and descending AWT are provided. In a healthy sample from the general population, the wall of the ascending aorta is thicker than the wall of the descending aorta, and both walls are thicker in males than females. The increase in wall thickness with age is greater in males., Key Points: Ascending aortic wall thickness is greater than descending aortic wall thickness. Ascending and descending aortic wall thickness is greater in males. Thoracic aortic wall thickness increases with age in both sexes. The age-related increase in aortic wall thickness is stronger in males.

Heschl's gyrus (HG) is a core region of the auditory cortex whose morphology is highly variable across individuals. This variability has been linked to sound perception ability in both speech and music domains. Previous studies show that variations in morphological features of HG, such as cortical surface area and thickness, are heritable. To identify genetic variants that affect HG morphology, we conducted a genome-wide association scan (GWAS) meta-analysis in 3054 healthy individuals using HG surface area and thickness as quantitative traits. None of the single nucleotide polymorphisms (SNPs) showed association P values that would survive correction for multiple testing over the genome. The most significant association was found between right HG area and SNP rs72932726 close to gene DCBLD2 (3q12.1; P=2.77 × 10(-7) ). This SNP was also associated with other regions involved in speech processing. The SNP rs333332 within gene KALRN (3q21.2; P=2.27 × 10(-6) ) and rs143000161 near gene COBLL1 (2q24.3; P=2.40 × 10(-6) ) were associated with the area and thickness of left HG, respectively. Both genes are involved in the development of the nervous system. The SNP rs7062395 close to the X-linked deafness gene POU3F4 was associated with right HG thickness (Xq21.1; P=2.38 × 10(-6) ). This is the first molecular genetic analysis of variability in HG morphology., (© 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Functional and anatomical asymmetries are prevalent features of the human brain, linked to gender, handedness, and cognition. However, little is known about the neurodevelopmental processes involved. In zebrafish, asymmetries arise in the diencephalon before extending within the central nervous system. We aimed to identify genes involved in the development of subtle, left-right volumetric asymmetries of human subcortical structures using large datasets. We first tested the feasibility of measuring left-right volume differences in such large-scale samples, as assessed by two automated methods of subcortical segmentation (FSL|FIRST and FreeSurfer), using data from 235 subjects who had undergone MRI twice. We tested the agreement between the first and second scan, and the agreement between the segmentation methods, for measures of bilateral volumes of six subcortical structures and the hippocampus, and their volumetric asymmetries. We also tested whether there were biases introduced by left-right differences in the regional atlases used by the methods, by analyzing left-right flipped images. While many bilateral volumes were measured well (scan-rescan r = 0.6-0.8), most asymmetries, with the exception of the caudate nucleus, showed lower repeatabilites. We meta-analyzed genome-wide association scan results for caudate nucleus asymmetry in a combined sample of 3,028 adult subjects but did not detect associations at genome-wide significance (P < 5 × 10(-8) ). There was no enrichment of genetic association in genes involved in left-right patterning of the viscera. Our results provide important information for researchers who are currently aiming to carry out large-scale genome-wide studies of subcortical and hippocampal volumes, and their asymmetries., (Copyright © 2013 Wiley Periodicals, Inc.)

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

Objectives: To evaluate body weight-tailored contrast medium (CM) administration for computed tomography angiography (CTA) of the craniocervical vessels., Methods: Institutional review board approval was obtained, and all patients gave written informed consent. Sixty patients were consecutively assigned to one of three dose groups (20 patients per group) with CM doses of Visipaque 270® (iodixanol 270 mg/ml) tailored to body weight at doses of 1.5, 1.0, or 0.5 ml/kg. Region-of-interest (ROI) analysis of maximum enhancement (ME) was conducted, and signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were calculated. Retrospective comparison was performed with three matched control groups examined with a standard CM dose (80 ml of Visipaque 270®). Image quality was rated by two neuroradiologists blinded to the CM dose used. Interrater reliability was calculated using kappa statistics., Results: Body weight/BMI and ME were inversely correlated in the three control groups receiving the standard dose (r = -0.544/-0.597/-0.542/r = -0.358/r = -0.424/r = -0.280). Compared to standard dose, 1.5 ml/kg produced higher ME, SNR, and CNR in the anterior circulation (p≤0.038), 1.0 ml/kg had higher ME in cervical and medium-sized cerebral arteries (p≤0.034), and 0.5 ml/kg had lower ME, SNR and CNR for medium-sized cerebral arteries (p≤0.049). ME, SNR, and CNR were the same for 1.5 ml/kg and 1.0 ml/kg (p≥0.24), and both had higher values compared to 0.5 ml/kg (p≤0.043/p≤0.028). In patients with BMI>25, 1.5 ml/kg and 1.0 ml/kg produced higher ME than standard dose (p<0.001/p = 0.008), but ME in patients with BMI>25 did not differ between group 1 and group 2 (p = 0.673). In patients with BMI≤25, 1.5 ml/kg and 1.0 ml/kg produced ME comparable to standard dose (p = 0.132/p = 0.403). Regardless of patient weight, 0.5 ml/kg yielded lower ME than standard dose (p = 0.019/0.002)., Conclusions: Craniocervical CTA with a body weight-tailored CM dose of 1.0 ml/kg (270 mg iodine/ml) reduces iodine load in patients weighing <80 kg while producing ME similar to standard dose and improves ME in patients with BMI>25.