Establishing Normative Values for Acromion Anatomy: A Comprehensive MRI-Based Study in a Healthy Population of 996 Participants.

Shoulder pain is a common issue often linked to conditions such as subacromial impingement or rotator cuff lesions. The role of the acromion in these symptoms remains a subject of debate. This study aims to establish standardized values for commonly used acromion dimensions based on whole-body MRI scans of a large and healthy population and to investigate potential correlations between acromion shape and influencing factors such as sex, age, BMI, dominant hand, and shoulder pain. The study used whole-body MRI scans from the Study of Health in Pomerania, a German population-based study. Acromion index, acromion tilt, and acromion slope were measured. Interrater variability was tested with two independent, trained viewers on 100 MRI sequences before actual measurements started. Descriptive statistics and logistic regression were used to evaluate the results. We could define reference values based on a shoulder-healthy population for each acromion parameter within the 2.5 to 97.5 percentile. No significant differences were found in acromion slope, tilt, and index between male and female participants. No significant correlations were observed between acromion morphology and anthropometric parameters such as height, weight, or BMI. No significant differences were observed in acromion parameters between dominant and non-dominant hands or stated pain intensity. This study provides valuable reference values for acromion-related parameters, offering insight into the anatomy of a healthy shoulder. The findings indicate no significant differences in acromion morphology based on sex, weight, BMI, or dominant hand. Further research is necessary to ascertain the clinical implications of these reference values. The establishment of standardized reference values opens new possibilities for enhancing clinical decision making regarding surgical interventions, such as acromioplasty.

The neck-shaft angle: an update on reference values and associated factors.

Background and purpose - The neck-shaft angle (NSA) is valuable for diagnostics and therapy of the hip, but current reference values derive mostly from studies on anatomic specimens, small cohorts, or are hospital-based. Moreover, associated factors such as age, sex, or anthropometric data have rarely been considered. Therefore, we determined associated factors for NSA and reassessed the historical reference values in a general adult population.Methods - NSAs on both sides of 3,226 volunteers from the population-based Study of Health in Pomerania (SHIP) were measured with MRI. SHIP drew a representative sample of the population of Pomerania (northeastern Germany). NSAs were compared with sex, age, and anthropometric data by bivariable linear regression models. Reference values were assessed by quantile regressions for 2.5th and 97.5th percentiles.Results - The mean NSA was 127° (SD 7), while men had a lower NSA than women (95% confidence interval [CI] 0.4°-1.4°). The reference range was 114°-140°. Age was inversely associated with NSA (CI -0.2 to -0.1). Body height was positively associated with the NSA, while BMI and waist circumference showed a negative association. There was no association between body weight and NSA.Interpretation - The historical lower limit of 120° might be too high, so the radiological prevalence of hip pathology might have been overestimated. The previously reported influence of age, sex, and body height on the NSA has been confirmed.

What Are the Reference Values and Associated Factors for Center-edge Angle and Alpha Angle? A Population-based Study.

BACKGROUND: The available evidence regarding normal ranges for the center-edge angle and the alpha angle derives from a few small studies, and associated factors such as sex and anthropometric factors have not been well evaluated. Knowing more about normal values for these parameters is critical, because this can inform decisions about when to perform elective hip preservation surgery. Population-level studies would provide considerable clarity on these issues, but to our knowledge, no such studies are available. QUESTIONS/PURPOSES: The purposes of this study were (1) to use MRI in patients of a population-based study to establish normal values for the alpha and center-edge angles in the normal adult hip; and (2) to determine whether age, sex, or anthropometric variables were associated with differences in these values. METHODS: We used MRI images (1.5 T) of 3226 participants of the Study of Health in Pomerania (SHIP). SHIP is a population-based study that started with 4308 participants in 1997. Participants were recruited randomly from official inhabitant data files as a stratified cluster sample of the population from a defined region in northeastern Germany. To ensure a representative epidemiologic cohort, stratification variables were sex, age, and city of residence. Between 2008 and 2012, 1094 of these participants underwent whole-body MRI with pelvic sequences in the second followup. In parallel, the next cohort, SHIP-Trend, started with the same protocol in which 2132 participants underwent MRI examination. Reference values were calculated by quantile regressions for the 2.5 and 97.5 percentiles. Associations with the demographic features sex, age, weight, height, body mass index (BMI), and waist circumference were analyzed by bivariate linear regression models. RESULTS: The mean center-edge angle was 31° (± 7°) with a corresponding calculated normal range of 17° to 45°. The mean alpha angle was 55° (± 8°) with a corresponding calculated normal range between 39° and 71°. Men (30° ± 7°) had a lower center-edge angle than women (32° ± 8°) (p < 0.001, ß = 1.4°; 95% confidence interval [CI], 0.9°-1.9°) and a higher alpha angle (57° ± 8° versus 52° ± 7°, p < 0.001, ß = 5.7°; 95% CI, 5.2°-6.3°). Moreover, a higher center-edge angle for the left side was found (33° ± 8° versus 30° ± 8°, p < 0.001, ß =3.2°; 95% CI, 3.0°-3.4°). In addition to sex, we found that age, height, waist circumference, and BMI affected both center-edge angle and alpha angle. Weight was associated with the alpha angle as well. Because of these associations, age- and sex-adjusted reference values with belonging formulas were calculated. CONCLUSIONS: The range of normal center-edge and alpha angles is quite wide. Therefore, only markedly abnormal angles may be associated with pathology. Moreover, center-edge angle and alpha angle are associated with age, sex, and anthropometric factors, which have to be taken into account for better interpretation. CLINICAL RELEVANCE: The association of abnormal radiographic values with true clinical hip pathology is tenuous at best. Assuming that a patient with an abnormal radiograph requires treatment is unwise. The clinical picture has to be substantial for therapeutic decisions.

Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation.

Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10-8; false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.

Preliminary findings of cerebral responses on transcutaneous vagal nerve stimulation on experimental heat pain.

Transcutaneous vagal nerve stimulation (TVNS) is a promising complementary method of pain relief. However, the neural networks associated with its analgesic effects are still to be elucidated. Therefore, we conducted two functional magnetic resonance imaging (fMRI) sessions, in a randomized order, with twenty healthy subjects who were exposed to experimental heat pain stimulation applied to the right forearm using a Contact Heat-Evoked Potential Stimulator. While in one session TVNS was administered bilaterally to the concha auriculae with maximal, non-painful intensity, the stimulation device was switched off in the other session (placebo condition). Pain thresholds were measured before and after each session. Heat stimulation elicited fMRI activation in cerebral pain processing regions. Activation magnitude in the secondary somatosensory cortex, posterior insula, anterior cingulate and caudate nucleus was associated with heat stimulation without TVNS. During TVNS, this association was only seen for the right anterior insula. TVNS decreased fMRI signals in the anterior cingulate cortex in comparison with the placebo condition; however, there was no relevant pain reducing effect over the group as a whole. In contrast, TVNS compared to the placebo condition showed an increased activation in the primary motor cortex, contralateral to the site of heat stimulation, and in the right amygdala. In conclusion, in the protocol used here, TVNS specifically modulated the cerebral response to heat pain, without having a direct effect on pain thresholds.

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.

Fully Automated Renal Tissue Volumetry in MR Volume Data Using Prior-Shape-Based Segmentation in Subject-Specific Probability Maps.

Organ segmentation in magnetic resonance (MR) volume data is of increasing interest in epidemiological studies and clinical practice. Especially in large-scale population-based studies, organ volumetry is highly relevant requiring exact organ segmentation. Since manual segmentation is time consuming and prone to reader variability, large-scale studies need automatic methods to perform organ segmentation. In this paper, we present an automated framework for renal tissue segmentation that computes renal parenchyma, cortex, and medulla volumetry in native MR volume data without any user interaction. We introduce a novel strategy of subject-specific probability map computation for renal tissue types, which takes inter- and intra-MR-intensity variability into account. Several kinds of tissue-related 2-D and 3-D prior-shape knowledge are incorporated in modularized framework parts to segment renal parenchyma in a final level set segmentation strategy. Subject-specific probabilities for medulla and cortex tissue are applied in a fuzzy clustering technique to delineate cortex and medulla tissue inside segmented parenchyma regions. The novel subject-specific computation approach provides clearly improved tissue probability map quality than existing methods. Comparing to existing methods, the framework provides improved results for parenchyma segmentation. Furthermore, cortex and medulla segmentation qualities are very promising but cannot be compared to existing methods since state-of-the art methods for automated cortex and medulla segmentation in native MR volume data are still missing.

Translating pharmacological findings from hypothyroid rodents to euthyroid humans: is there a functional role of endogenous 3,5-T2?

BACKGROUND: During the last two decades, it has become obvious that 3,5-diiodothyronine (3,5-T2), a well-known endogenous metabolite of the thyroid hormones thyroxine (T4) or triiodothyronine (T3), not only represents a simple degradation intermediate of the former but also exhibits specific metabolic activities. Administration of 3,5-T2 to hypothyroid rodents rapidly stimulated their basal metabolic rate, prevented high-fat diet-induced obesity as well as steatosis, and increased oxidation of long-chain fatty acids. OBJECTIVE: The aim of the present study was to analyze associations between circulating 3,5-T2 in human serum and different epidemiological parameters, including age, sex, or smoking, as well as measures of anthropometry, glucose, and lipid metabolism. METHODS: 3,5-T2 concentrations were measured by a recently developed immunoassay in sera of 761 euthyroid participants of the population-based Study of Health in Pomerania. Subsequently, analysis of variance and multivariate linear regression analysis were performed. RESULTS: Serum 3,5-T2 concentrations exhibited a right-skewed distribution, resulting in a median serum concentration of 0.24 nM (1st quartile: 0.20 nM; 3rd quartile: 0.37 nM). Significant associations between 3,5-T2 and serum fasting glucose, thyrotropin (TSH), as well as leptin concentrations were detected (p<0.05). Interestingly, the association to leptin concentrations seemed to be mediated by TSH. Age, sex, smoking, and blood lipid profile parameters did not show significant associations with circulating 3,5-T2. CONCLUSION: Our findings from a healthy euthyroid population may point toward a physiological link between circulating 3,5-T2 and glucose metabolism.

A level set based framework for quantitative evaluation of breast tissue density from MRI data.

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.

Transcutaneous vagal nerve stimulation may elicit anti- and pro-nociceptive effects under experimentally-induced pain - a crossover placebo-controlled investigation.

Vagal nerve stimulation is a promising method for the treatment of pain. The aim was to investigate the effect of non-invasive transcutaneous vagal nerve stimulation (TVNS) on the experimental pain threshold (PT) and to compare it with placebo. PT of standardized electrical stimulation was measured in 22 healthy male volunteers during two study sessions. TVNS was applied to the auricular concha bilaterally for 35min using 2Hz/100Hz bursts with the intensity, which was individually maximal but non-painful. During the placebo session, the volunteers received no stimulation. PT, heart rate and blood pressure were registered as outcome measures. There were no differences in PT values between TVNS and placebo conditions in the group analysis. Fifteen volunteers (responders) reacted with an increase in PT during TVNS (p<0.01 vs. baseline) but not during the placebo session. Another six participants reported decreased PT during and after TVNS (p<0.05 vs. baseline), but not during the placebo session. Heart rate and blood pressure did not change during the study. Transcutaneous vagal nerve stimulation may produce both anti- and pro-nociceptive effects in healthy volunteers. The individual sensitivity and TVNS parameters might play a role.

Proton-density fat fraction and simultaneous R2* estimation as an MRI tool for assessment of osteoporosis.

OBJECTIVE: To investigate multi-echo chemical shift-encoded MRI-based mapping of proton density fat fraction (PDFF) and fat-corrected R2* in bone marrow as biomarkers for osteoporosis assessment. METHODS: Fifty-one patients (28 female; mean age 69.7 ± 9.0 years) underwent dual energy X-ray absorptiometry (DXA). On the basis of the t score, 173 valid vertebrae bodies were divided into three groups (healthy, osteopenic and osteoporotic). Three echo chemical shift-encoded MRI sequences were acquired at 3 T. PDFF and R2* with correction for multiple-peak fat (R2*MP) were measured for each vertebral body. Kruskal-Wallis test and post hoc analysis were performed to evaluate differences between groups. Further, the area under the curve (AUC) for each technique was calculated using logistic regression analysis. RESULTS: On the basis of DXA, 92 samples were normal (53 %), 47 osteopenic (27 %) and 34 osteoporotic (20 %). PDFF was increased in osteoporosis compared with healthy (P = 0.007). R2*MP showed significant differences between normal and osteopenia (P = 0.004), and between normal and osteoporosis (P < 0.001). AUC to differentiate between normal and osteoporosis was 0.698 for R2*MP, 0.656 for PDFF and 0.74 for both combined. CONCLUSION: PDFF and R2*MP are moderate biomarkers for osteoporosis. PDFF and R2*MP combination might improve the prediction in differentiating healthy subjects from those with osteoporosis.

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.

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.

Prior shape level set segmentation on multistep generated probability maps of MR datasets for fully automatic kidney parenchyma volumetry.

Fully automatic 3-D segmentation techniques for clinical applications or epidemiological studies have proven to be a very challenging task in the domain of medical image analysis. 3-D organ segmentation on magnetic resonance (MR) datasets requires a well-designed segmentation strategy due to imaging artifacts, partial volume effects, and similar tissue properties of adjacent tissues. We developed a 3-D segmentation framework for fully automatic kidney parenchyma volumetry that uses Bayesian concepts for probability map generation. The probability map quality is improved in a multistep refinement approach. An extended prior shape level set segmentation method is then applied on the refined probability maps. The segmentation quality is improved by incorporating an exterior cortex edge alignment technique using cortex probability maps. In contrast to previous approaches, we combine several relevant kidney parenchyma features in a sequence of segmentation techniques for successful parenchyma delineation on native MR datasets. Furthermore, the proposed method is able to recognize and exclude parenchymal cysts from the parenchymal volume. We analyzed four different quality measures showing better results for right parenchymal tissue than for left parenchymal tissue due to an incorporated liver part removal in the segmentation framework. The results show that the outer cortex edge alignment approach successfully improves the quality measures.

A fast and accurate automatic lung segmentation and volumetry method for MR data used in epidemiological studies.

In modern epidemiological population-based studies a huge amount of magnetic resonance imaging (MRI) data is analysed. This requires reliable automatic methods for organ extraction. In the current paper, we propose a fast and accurate automatic method for lung segmentation and volumetry. Our approach follows a "coarse-to-fine" segmentation strategy. First, we extract the lungs and trachea excluding the main pulmonary vessels. This step is executed very fast and allows for measuring the volume of both structures. Thereafter, we start a refinement procedure that consists of three main stages: trachea extraction, lung separation, and filling the cavities on the final lung masks. After the trachea extraction step the volumes of both lungs without the main vessels can be measured. The final segmentation step results in the volumes of the left and right lungs including the vessels. The method has been tested by processing MR datasets from ten healthy participants. We compare our results with manually produced masks and obtain high agreement between the expert reading and our method: the True Positive Volume Fraction is more than 95%. The proposed automatic approach is fast and accurate enough to be applied in clinical routine for processing of thousands of participants.