Effects of whole-body MRI on outpatient health service costs: a general-population prospective cohort study in Mecklenburg-Vorpommern, Germany.

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.

SHIP-MR and Radiology: 12 Years of Whole-Body Magnetic Resonance Imaging in a Single Center.

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.

Recall accuracy of notifications about incidental findings from an MRI examination: results from a population-based study.

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.

Correlation of Ductoscopic and Histopathological Findings and Their Relevance as Predictors for Malignancy: A German Multicenter Study.

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.

Reference values for the cervical spinal canal and the vertebral bodies by MRI in a general population.

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.

A deep learning framework for efficient analysis of breast volume and fibroglandular tissue using MR data with strong artifacts.

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.

Association between Serum Thyroid-Stimulating Hormone Levels and Visceral Adipose Tissue: A Population-Based Study in Northeast Germany.

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 (ß = 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.

Domains of physical activity and brain volumes: A population-based study.

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.

Childhood adversity impacts on brain subcortical structures relevant to depression.

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.

White matter hyperintensities and imaging patterns of brain ageing in the general population.

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.

Effect of the interaction between childhood abuse and rs1360780 of the FKBP5 gene on gray matter volume in a general population sample.

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.

An efficient level set method for simultaneous intensity inhomogeneity correction and segmentation of MR images.

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.

Chronic Back Pain Is Associated With Decreased Prefrontal and Anterior Insular Gray Matter: Results From a Population-Based Cohort Study.

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.

3D Regression Heat Map Analysis of Population Study Data.

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.

Impact of whole-body MRI in a general population study.

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 ß = -0.06 (95% CI -0.30 to 0.18); MCS: ß = -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: ß = -0.03 (-0.39 to 0.33); MCS: ß = -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.

Needle decompression of tension pneumothorax: Population-based epidemiologic approach to adequate needle length in healthy volunteers in Northeast Germany.

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.

Thoracic and abdominal aortic diameters in a general population: MRI-based reference values and association with age and cardiovascular risk factors.

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 (ß = -0.049, p < 0.001), the aortic arch (ß = -0.061, p < 0.001) and the subphrenic aorta (ß = -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 (ß = 0.001; 0.004) and HDL (ß = 0.035; 0.087) with BSA-adjusted aortic diameters and for an inverse association of systolic BP (ß = -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.

Association between waist circumference and gray matter volume in 2344 individuals from two adult community-based samples.

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.

Whole-Body MR Imaging in the German National Cohort: Rationale, Design, and Technical Background.

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.

Association of a neurokinin 3 receptor polymorphism with the anterior basal forebrain.

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.