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.

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.

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.

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.

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.

Pancreatic Steatosis Demonstrated at MR Imaging in the General Population: Clinical Relevance.

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.

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.

Cardiovascular risk factors and thoracic aortic wall thickness in a general population.

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 (ß = .086, P < .001), age (ß = .006, P < .001), and BMI (ß = .013, P < .001) were positively associated with the AWT of the ascending aorta. Male sex (ß = .105, P < .001), age (ß = .006, P < .001), current smoker (ß = .044, P = .010), BMI (ß = .013, P < .001), and HDL-C (ß = .057, P = .008) revealed a positive association with AWT of the descending aorta. LDL-C (ß = -.024, P = .009; ß = -.018, P = .010) was inversely associated with the AWT of the ascending and descending aorta, respectively. Triglyceride levels (ß = .024, P = .027; ß = .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.

A genome-wide association study identifies five loci influencing facial morphology in Europeans.

Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs) and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes--PRDM16, PAX3, TP63, C5orf50, and COL17A1--in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications.

Alexithymia and brain gray matter volumes in a general population sample.

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.

Measurement and genetics of human subcortical and hippocampal asymmetries in large datasets.

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.

MRI-based determination of reference values of thoracic aortic wall thickness in a general population.

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.

Normal breast parenchyma: contrast enhancement kinetics at dynamic MR mammography--influence of anthropometric measures and menopausal status.

PURPOSE: To study T1 baseline signal intensity (SI) and contrast material enhancement kinetics of normal breast parenchyma by using dynamic contrast-enhanced (DCE) magnetic resonance (MR) mammography and to determine the influence of anthropometric measures and menopausal status on the variability of these features. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Between June 2008 and September 2011, 345 women (age range, 26-81 years; mean age, 51.3 years ± 11.6 [standard deviation]) underwent DCE MR mammography, with T1-weighted three-dimensional MR images (repetition time msec/echo time msec, 8.86/4.51; flip angle, 25°) acquired with a 1.5-T whole-body MR unit before and 1, 2, 3, 4, and 5 minutes after a gadobutrol bolus injection of 0.1 mmol per kilogram of body weight. Regions of interest were traced manually, and T1 SI of parenchyma was recorded. The influence of different predictors of T1 baseline SI and contrast enhancement was studied by using random-effects models. RESULTS: T1 baseline SI varied considerably between women, with a mean of 167.7 ± 49.2 (71.4-424.7 [range]) and 175.9 ± 48.9 (51.8-458.3) in the right and the left breast, respectively (P < .01). T1 baseline SI increased linearly with age (P < .0001) and body weight (P < .0001). After contrast material delivery, relative percentage of enhancement was 8.1%, 13.8%, 18.2%, 22.1%, and 24.6% at 1, 2, 3, 4, and 5 minutes, respectively, but varied considerably between women. Contrast enhancement was 9.3% in the lowest quintile and 47.4% in the highest. Contrast enhancement increased with body weight (P < .01) but decreased in postmenopausal women (P < .01). Women with higher baseline T1 SI tended to have a higher contrast enhancement slope. CONCLUSION: Anthropometric measures and menopausal status contribute to a large variability in contrast enhancement of normal breast parenchyma. This might influence the interpretation of contrast enhancement kinetics of breast lesions and current strategies for determining contrast medium dose for breast MR imaging.

Potentially relevant incidental findings on research whole-body MRI in the general adult population: frequencies and management.

OBJECTIVES: To report the frequencies of potentially relevant incidental findings in the general adult population and to develop a protocol for their management in whole-body magnetic resonance imaging (wb-MRI). METHODS: A total of 2,500 adult subjects (1,271 women, 1,229 men; mean age 53 years) from the population-based Study of Health in Pomerania underwent standardised wb-MRI. Additionally, 1,129 participants received contrast-enhanced cardiac MRI, 619 men received MR angiography and 544 women received MR mammography. Two independent residents performed first-line reading. A third reader resolved disagreements. An interdisciplinary advisory board decided about disclosure. RESULTS: There were 1,330 incidental findings of potential clinical relevance in 904 subjects (36.2 %). Nine findings (0.4 %) required immediate referral. In total, 1,052 findings (79.1 %) were confirmed by the advisory board and disclosed to 787 participants (31.5 %). The abdominal organs (6.8 %), the urinary tract (6.8 %) and the skeletal system (6.0 %) were affected most often. While 383 findings (36.4 %) were indicated as benign and 62 (5.9 %) as malignant, most abnormalities, 607 (57.7 %), were of an unclear nature. CONCLUSIONS: Potentially relevant incidental findings are very common in wb-MRI research but the nature of these findings remains unclear in most cases. This requires dedicated management to protect subjects' welfare and research integrity.

Psychosocial consequences and severity of disclosed incidental findings from whole-body MRI in a general population study.

OBJECTIVES: Little is known about the psychosocial impact and subjective interpretation of communicated incide ntal findings from whole-body magnetic resonance imaging (wb-MRI). This was addressed with this general population study. METHODS: Data was based on the Study of Health in Pomerania (SHIP), Germany. SHIP comprised a 1.5-T wb-MRI examination. A postal survey was conducted among the first 471 participants, aged 23-84 years, who received a notification about incidental findings (response 86.0 %, n = 405). The severity of incidental findings was assessed from the participants' and radiologists' perspective. RESULTS: In total, 394 participants (97.3 %) wanted to learn about their health by undergoing wb-MRI. Strong distress while waiting for a potential notification of an incidental finding was reported by 40 participants (9.9 %), whereas 116 (28.6 %) reported moderate to severe psychological distress thereafter. Strong disagreement was noted between the subjective and radiological evaluation of the findings' severity (kappa = 0.02). Almost all participants (n = 389, 96.0 %) were very satisfied with their examination. CONCLUSIONS: Despite the high satisfaction of most participants, there were numerous adverse consequences concerning the communication of incidental findings and false expectations about the likely potential benefits of whole-body-MRI. KEY POINTS: • Disclosed incidental findings from MRI may lead to substantial psychosocial distress. • Subjective and radiological evaluations of incidental findings' severity differ strongly. • Disclosing incidental findings is strongly endorsed by study volunteers. • Study volunteers tend to have false expectations about potential benefits from MRI. • Minimizing stress in study volunteers should be a key aim in MRI research.

Nipple discharge: role of ductoscopy in comparison with standard diagnostic tests.

BACKGROUND: This study aims to assess the role of ductoscopy for detecting intraductal anomalies in patients with nipple discharge in comparison to conventional tests and to find an effective combination of both approaches. MATERIALS AND METHODS: Prior to duct excision, ductoscopy was performed in 97 women. Histologic and all other diagnostic results were compared. Sensitivity, specificity, and efficiency were calculated for all methods. These parameters were also calculated for all possible test combinations in 12 patients who had completed all tests. RESULTS: Breast sonography reached the highest sensitivity (64.1%) and efficiency (64%); mammography had the highest specificity (100%). The sensitivity of ductoscopy was 53.2%, its specificity 60%, and its efficiency 55.1%. Among combinations of all methods, the combination ductoscopy + galactography was the most sensitive (80%). Mammography, magnetic resonance imaging, and ductoscopy were each 100% specific. Ductoscopy was the most efficient (75%) single method. CONCLUSION: Ductoscopy is a valuable test for diagnosing intraductal lesions in patients with nipple discharge. It is more efficient than conventional tests in patients undergoing all tests.

Contrast enhancement kinetics of normal breast parenchyma in dynamic MR mammography: effects of menopausal status, oral contraceptives, and postmenopausal hormone therapy.

OBJECTIVES: To investigate effects of menopausal status, oral contraceptives (OC), and postmenopausal hormone therapy (HT) on normal breast parenchymal contrast enhancement (CE) and non-mass-like enhancing areas in magnetic resonance mammography (MRM). METHODS: A total of 459 female volunteers (mean age 49.1 ± 12.5 years) underwent T1-weighted 3D MRM 1-5 min after bolus injection of gadobutrol. Quantitative analysis was performed in normal breast parenchyma by manually tracing regions of interest and calculating percentage CE. Semiquantitative analysis was performed in non-mass-like enhancing areas, and signal intensity changes were characterised by five predefined kinetic curve types. The influence of OC (n = 69) and HT (n = 24) on CE was studied using random effects models. RESULTS: Breast parenchymal enhancement was significantly higher in premenopausal than in postmenopausal women (P < 0.001). CE decreased significantly with the use of OC (P = 0.01), while HT had negligible effects (P = 0.52). Prevalence of kinetic curve types of non-mass-like enhancement differed strongly between pre- and postmenopausal women (P < 0.0001), but was similar in OC users and non-OC users (P = 0.61) as well as HT users and non-HT users (P = 0.77). CONCLUSIONS: Normal breast parenchymal enhancement and non-mass-like enhancing areas were strongly affected by menopausal status, while they were not affected by HT use and only moderately by OC use. KEY POINTS: Breast parenchymal enhancement at MR mammography is stronger in premenopausal than postmenopausal women. The prevalence of strong enhancing non-mass-like areas is greater before menopause. Such enhancing non-mass-like areas may impair lesion detection in premenopausal women. Breast parenchymal enhancement is only marginally affected by hormone use. Discontinuation of hormone use before MR mammography may be unnecessary.

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.

Spontaneous haemoptysis as a late complication of plombage in a tuberculosis patient.

The endemic spread of tuberculosis after World War II and the deficiency of appropriate antituberculous drugs had led to a renaissance of the surgical tuberculosis therapy until the early 1950s. Late complications of plombage performed decades before are rare and are mainly related to infection and/or migration of the inserted foreign material and are scarcely recognized today. We report on a 73-year-old male patient, who was admitted to the emergency room of our hospital with acute massive haemoptysis for four days. On physical examination the patient presented with decreased breath sounds over the left lung and an old left-sided thoracotomy scar. Radiological findings and bronchoscopy revealed an empyema and a fistula as late complications 53 years after collapse therapy with insertion of a plombage for the treatment of pulmonary tuberculosis. The endobronchial nylon threads in the left bronchial tree and the fistula ending in the left lower bronchus confirmed our diagnosis. The patient was successfully treated by resection of the affected lower lobe. The present casuistic demonstrates a rare cause of spontaneous haemoptysis: late complications after extrapleural pneumolysis and plombage for cavitary tuberculosis over 50 years after the initial operation.