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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., Competing Interests: TS and MK have consulted for Identitas Inc. and are on the SAB but without financial or other direct benefits. All other authors have declared that no competing interests exist.

Rationale and Objectives: This study evaluates the validity and reliability of measuring the diameters of the thoracic and abdominal aorta from plain volumetric interpolated breath-hold examination (VIBE) images., Materials and Methods: The study included 50 male subjects from the population-based Study of Health in Pomerania. They underwent imaging of the thoracic and abdominal aorta at 1.5 Tesla using a contrast-enhanced magnetic resonance angiography (CE-MRA) and plain VIBE sequence. Diameters were measured at five predefined anatomic sites from reformatted orthogonal CE-MRA images and axial plain VIBE images. The measurements were validated using Pearson correlation and Bland-Altman analysis. The Bland-Altman method was also used to assess reliability., Results: Comparison of the diameters measured from CE-MRA and VIBE images revealed strong correlation for the ascending, descending, suprarenal, and infrarenal aorta with r = 0.95 (P < .0001), r = 0.88 (P < .0001), 0.92 (P < .0001), and 0.87 (P < .0001), respectively. Measurement for the aortic arch was moderately correlated with r = 0.78 (P < .0001). Mean bias did not exceed 0.1 cm (6%). The 95% limits of agreement (LOA) were less than 0.5 cm (15%). Intra- and interobserver agreement showed a mean bias of less than 2%; the 95% LOA were less than 11%., Conclusions: Axial measurement of the diameters of the thoracic and abdominal aorta using a plain axial VIBE sequence is highly valid and reliable, making it suitable for use in epidemiologic research., (Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to determine the accuracy and reliability of Frankfort horizontal plane identification using displays of multi-planar reconstructed MRI images, and propose it as a sufficiently stable and standardized reference plane for craniofacial structures., Materials and Methods: MRI images of 43 subjects were obtained from the longitudinal population based cohort study SHIP-2 using a T1-weighted 3D sequence. Five examiners independently identified the three landmarks that form FH plane. Intra-examiner reproducibility and inter-examiner reliability, correlation coefficients (ICC), coefficient of variability and Bland-Altman plots were obtained for all landmarks coordinates to assess reproducibility. Intra-examiner reproducibility and inter-examiner reliability in terms of location and plane angulation were also assessed., Results: Intra- and inter-examiner reliabilities for X, Y and Z coordinates of all three landmarks were excellent with ICC values ranging from 0.914 to 0.998. Differences among examiners were more in X and Z than in Y dimensions. The Bland-Altman analysis demonstrated excellent intra- as well as inter-examiner agreement between examiners in all coordinates for all landmarks. Intra-examiner reproducibility and inter-examiner reliability of the three landmarks in terms of distance showed mean differences between 1.3 to 2.9 mm, Mean differences in plane angulation were between 1.0° to 1.5° among examiners., Conclusion: This study revealed excellent intra-examiner reproducibility and inter-examiner reliability of Frankfort Horizontal plane through 3D landmark identification in MRI. Sufficiently stable landmark-based reference plane could be used for different treatments and studies.

Background: The thickness and composition of the chest wall are important quantities in multiparametric trauma models for the assessment of injury severity due to blunt ballistic chest impact. While ballistic parameters of non-penetrating projectiles can routinely be measured with high accuracy, data on the thickness of the anterior chest wall is unreliable. Therefore, it is the aim of this work to provide data on the thickness and composition of the anterior chest wall based on MRI examinations of healthy volunteers and to compare these measurements with different empirical estimation rules for the chest wall thickness., Methods: The study encompassed consecutive male patients from an ongoing population-based cohort study. Each subject underwent standardized whole-body MRI (1.5Tesla). Thickness of total chest wall (CWT) and of adipose tissue (AT) were measured by two independent readers at ten anatomic locations on two cross-sectional planes over the centre of the left ventricle and over the tracheal bifurcation. For each subject, chest wall thickness was estimated based on ten different empirical estimation rules and percent errors were calculated., Results: The study encompassed 250 male volunteers (average age 55.5 years, range 21-84 years, SD 13.6 years). Mean intraclass correlation coefficient of the two readers was 0.90 (range 0.59-1.0, SD 0.08). Average CWT was 31.2mm (range 17.3-51.6mm, SD 5.8mm) while average thickness of AT was 13.1mm (range 3.6-26.7mm, SD 4.6mm). Relative adiposity was 0.41 on average (range 0.19-0.61, SD 0.09). There was significant correlation between CWT and body weight and between CWT and body mass index. Sturdivan's approximation formula showed strong correlation with the measured values (percent error 3.58%, SD 16.26%)., Conclusion: In this population, Sturdivan's equation formula which is based on the individual's body weight provides valid approximation values for the chest wall thickness and may be used for the optimal design of protective devices and personal body armor as well as for the development of anthropomorphic based test methodologies., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: In Germany, a mammography-screening program (MSP) was implemented on a national level. It complies with all criteria of the European guidelines for quality assurance in screening mammography; however, the attendance rate is 54%, falling short of the target attendance rate of 70%. The aim of this study was to investigate whether additional telephone counseling improves attendance among nonresponders and the level of satisfaction with telephone counseling., Design: In a prospective RCT, women identified as nonresponders in the MSP were randomized to a control group that received written reminders or to an intervention group that additionally received telephone counseling. In a follow-up, a subset of the intervention group was contacted by telephone regarding their satisfaction with telephone counseling., Setting/participants: In 2008, a total of 5477 women aged 50-69 years who were eligible for the German MSP but had not participated up to 6 weeks after the first invitation were included in the study., Interventions: Individual telephone counseling consisted of scripted calls from a trained counselor who provided information on MSP and answered the woman's questions., Main Outcome Measures: Report of mammography use provided by the screening unit 3 months after the reminder was sent., Results: Analysis was conducted in 2009. Comparison of screening attendance revealed a significantly higher attendance rate in the intervention group compared with controls (29.7% vs 26.1%, p=0.0035). When only women for whom telephone numbers were available were analyzed, attendance was even better (35.5% vs 29.7%, p=0.0004). In the follow-up, 278 of 404 women were actually surveyed. Of those, 33% stated that telephone counseling had influenced their decision, 56% stated that they had undergone screening mammography, and 77% agreed that personal telephone counseling should be used routinely to encourage nonresponders to go for screening., Conclusions: Individual telephone counseling for nonresponders to a national program for breast cancer screening was well accepted by participants and effective., Trial Registration: This study is registered at the Australian New Zealand Clinical Trials Registry ACTRN12611000645954., (Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To investigate the feasibility and handling of abdominal MRI-guided biopsies in a 3-T MRI system., Methods: Over a 1-year period, 50 biopsies were obtained in 47 patients with tumours of the upper abdominal organs guided by 3-T MRI with a large-bore diameter of 70 cm. Lesions in liver (47), spleen (1) and kidney (2) were biopsied with a coaxial technique using a 16-G biopsy needle guided by a T1-weighted three-dimensional gradient recalled echo volumetric interpolated breath-hold examination (T1w-3D-GRE-VIBE) sequence. Sensitivity, specificity, accuracy, complication rate, interventional complexity, room/intervention time and needle artefacts were determined., Results: A sensitivity of 0.93, specificity of 1.0 and accuracy of 0.94 were observed. Three patients required a rebiopsy. There was a minor complications rate of 13.6%, and no major complications were observed. Histopathology revealed 38 malignant lesions, and 3-month follow-up confirmed 9 benign lesions. Mean lesion diameter was 3.4 ± 3.1 cm (50% being smaller than 2 cm). Mean needle tract length was 10.8 ± 3.3 cm. Median room time was 42.0 ± 19.8 min and intervention time 9.3 ± 8.1 min. Needle artefact size was about 9-fold greater for perpendicular access versus access parallel to the main magnetic field., Conclusion: Biopsies of the upper abdomen can be performed with great technical success and easy handling because of the large-bore diameter. The MRI-guided biopsy needle had an acceptable susceptibility artefact at 3 T. However future research must aim to reduce the susceptibility effects of the biopsy systems.

Objective: The objective of our study was to use perfusion CT to prospectively monitor early vascular changes in tumor perfusion of pulmonary metastases after laser-induced thermotherapy (LITT) and to determine whether any of the perfusion parameters would predict technical success after therapy., Subjects and Methods: Twelve patients with histologically proven pulmonary metastases undergoing LITT were enrolled prospectively in this study. Perfusion CT was performed before treatment, 1 day after treatment, and 4-6 weeks after therapy, and tumor blood flow, tumor blood volume (TBV), mean transit time (MTT), and permeability of the capillary wall surface (capillary permeability-surface product) in 22 pulmonary metastases were calculated. Perfusion parameters at baseline and after LITT were compared. Measurement of tumor diameter on long-term follow-up CT was the gold standard with which perfusion CT results were compared for local control., Results: Median tumor blood flow, TBV, and capillary permeability-surface product had decreased significantly from baseline by 43%, 61%, and 73%, respectively, 1 day after LITT. Perfusion parameters obtained 4-6 weeks after treatment had not changed significantly compared with those obtained 1 day after therapy. There seems to be a good correlation between changes in perfusion CT parameters 1 day after therapy and local outcome, according to the Response Evaluation Criteria in Solid Tumors (RECIST), 1 year after therapy., Conclusion: Perfusion CT of pulmonary metastases has potential in the assessment of early vascular changes that result from LITT and predicting technical success immediately after treatment. Tumors with perfusion measurements that had not changed after therapy indicated progressive disease.

Objective: The purpose of this study was to investigate whether, at dynamic MRI of the upper abdominal organs, contrast enhancement with gadoxetic acid, a hepatobiliary contrast agent, is comparable with that achieved with an extracellular contrast agent., Subjects and Methods: Dynamic gadoxetic acid-enhanced MRI of the pancreas, spleen, kidney, liver, and abdominal aorta was performed on 50 patients; dynamic gadobutrol-enhanced MRI was performed on a control group of 50 patients; and the images were compared. Dynamic imaging with a T1-weighted volumetric interpolated breath-hold examination gradient-echo sequence (TR/TE, 3.35/1.35; flip angle, 12 degrees ) was performed before and 20 (arterial phase), 55 (portal venous phase), and 90 (hepatic venous phase) seconds after bolus injection of gadoxetic acid (0.25 mmol/mL) or gadobutrol (1.0 mmol/mL). Signal-to-noise ratios and enhancement indexes were calculated for each organ and time., Results: All MR images in both groups were of diagnostic quality. During the early dynamic phases, significantly lower mean enhancement indexes were found in the gadoxetic acid group than in the gadobutrol group in the pancreas (portal venous phase, 0.66, 1.39, p

Purpose: Approximately 4000 volunteers will undergo whole-body magnetic resonance imaging (WB-MRI) within the next 3 years in the population-based Study of Health in Pomerania (SHIP). Here we present a pilot study conducted (a) to determine the feasibility of adding a WB-MRI protocol to a large-scale population-based study, (b) to evaluate the reliability of standardized MRI interpretation, and (c) to establish an approach for handling pathological findings., Materials and Methods: The institutional review board approved the study, and oral and written informed consent was obtained from each participant. Two hundred healthy volunteers (99 women, 101 men; mean age 48.3 years) underwent a standardized WB-MRI protocol. The protocol was supplemented by contrast-enhanced cardiac MRI and magnetic resonance (MR) angiography in 61 men (60.4%) and cardiac MRI and MR mammography in 44 women (44.4%). MR scans were evaluated independently by two readers. Abnormalities were discussed by an advisory board and classified according to the need for further clinical work-up., Results: One hundred ninety-four (97.0%) WB-MRI examinations were successfully completed in a mean scan time per subject of 90 minutes. There were 431 pathological findings in 176 (88%) of the participants. Of those 45 (10.4%) required further clinical work-up and 386 (89.6%) characterized as benign lesions did not. The interobserver agreement for the detection of pathological findings was excellent (kappa = 0.799)., Conclusion: The preliminary results presented here indicate that a large prospective, population-based study using WB-MRI is feasible and that the results of image analysis are reproducible. A variety of positive findings provide valuable information regarding disease prevalence in a general adult population.

We report a 47-year-old women who presented to her general practitioner and our hospital with weight loss of unknown etiology. Eight years previously she had undergone a hemithyroidectomy for nodular goiter with one cold nodule. Laboratory results revealed hypercalcemia, evidence of primary hyperparathyroidism and computer tomography of the thorax showed bilateral pulmonary metastasis. After undergoing CT-guided biopsy of a metastasis, histology revealed an endocrine primary tumor with low parathyroid hormone expression. In view of the history, clinical and biochemical findings we diagnosed a recently metastasized functioning parathyroid carcinoma, which eight years previously has been labeled as a benign atypical thyroid adenoma. The patient underwent surgical resection of all detected metastases. Afterwards the serum calcium and parathyroid hormone levels normalized. Parathyroid carcinoma is an uncommon tumor. In the absence of pathognomonic diagnostic criteria a definitive pathological diagnosis of parathyroid carcinoma often is not possible. The treatment of parathyroid carcinoma is essentially surgical. Patients with parathyroid carcinoma mostly die from uncontrollable hypercalcemia rather than from other tumor-related complications.

Objective: Pulmonary metastatic lesions are present in 20-54% of all patients who die of cancer. Surgical studies have shown that local management of distant tumor metastasis as part of multimodal cancer therapy improves survival. Minimally invasive procedures such as thermal ablation are still to prove their clinical relevance. The aim of this study was to monitor therapeutic outcome and long-term results after percutaneous laser-induced thermal ablation., Subjects and Methods: Sixty-four patients with metastasis to the lung underwent laser-induced thermal ablation in an ongoing prospective study. A total of 129 percutaneous procedures were performed to manage a total of 108 lung lesions. The median tumor size was 2.0 cm (range, 0.4-8.5 cm). Adequate management of all known individual tumor correlates was critical for definitive patient therapy. The Kaplan-Meier method was used to calculate survival and recurrence rates., Results: Definitive management of initial pulmonary disease was achieved in 31 of 64 patients. The 1-, 2-, 3-, 4-, and 5-year survival rates after ablative therapy were 81%, 59%, 44%, 44%, and 27%. The median progression-free interval was 7.4 months. There were no therapy-related deaths. Pneumothorax occurred in 38% of the patients, necessitating periprocedural drainage in 5% of all cases. Parenchymal bleeding (13% of cases) always was self-limited., Conclusion: Laser ablative therapy for pulmonary metastasis is a promising option in multimodal cancer therapy. The procedure is safe and effective. The initial clinical outcome data strongly suggest that this technique has the potential to improve survival among selected patients.

Purpose: To determine technical success, technique effectiveness, complications, and survival after laser ablation of liver metastases from colorectal cancer., Materials and Methods: Eighty-seven consecutive patients (65 men and 22 women; mean age, 62.8 years) with 180 liver metastases from colorectal carcinoma were included between 1998 and 2005. They underwent laser ablation with magnetic resonance (MR) thermometry in 170 sessions. Indications for laser ablation were locally unresectable tumors (16.1%), metastases in both liver lobes (34.5%), and refusal of surgery and/or general contraindications to surgery (49.4%). Technical success, technique effectiveness, and complication and survival rates were evaluated retrospectively., Results: Technical success was achieved in 178 of 180 sessions (99%). Follow-up after 24-48 hours demonstrated an effectiveness rate of 85.6%. Local tumor progression rate was 10% after 6 months. Major complications included large pleural effusion, large subcapsular hematoma, abscess, large pneumothorax, pleuritis with fever, intrahepatic hemorrhage, and biloma. Mean survival from the time of diagnosis of the primary tumor was 50.6 months for all patients treated (95% CI, 44.9-56.3 months). Median survival time was 54 months and survival rates were 95.7% at 1 year, 86.2% at 2 years, 72.4% at 3 years, 50.1% at 4 years, and 33.4% at 5 years. The mean survival time after the first treatment was 31.1 months (95% CI, 26.9-35.3 months)., Conclusions: Laser ablation of liver metastases of colorectal cancer with MR thermometry appears safe and efficacious. Although the results are encouraging, direct comparison with other ablative modalities in a prospective clinical trial would be necessary to definitely show one modality is superior.

Purpose: To evaluate the use of three-dimensional (3D) gradient-echo (GRE) magnetic resonance imaging (MRI) for percutaneous MR-guided catheter placement for laser therapy of liver metastases., Materials and Methods: Thirty-four patients were included. A total of 122 MR-guided percutaneous punctures of 67 liver metastases were performed on a 1.5T scanner (Symphony and Sonata; Siemens, Erlangen, Germany) using a 5.5F microcatheter system and titanium needle (Monocath; MeoMedical, Augsburg, Germany). In 88 of 122 procedures, a 2D fast low-angle shot (FLASH) T1-weighted GRE breath-hold sequence was acquired in the axial plane and if necessary in a second plane. Sequences were acquired and reviewed using the panel in the control room. In 34 of 122 procedures a 3D FLASH T1-weighted fat-saturated GRE (volume-interpolated breath-hold examination (VIBE)) sequence was acquired in the axial plane only. Acquisition and 3D review were controlled under sterile conditions with a panel inside the examination room (Syngo; Siemens)., Results: The 3D FLASH sequence significantly decreased the mean number of acquisitions needed to place the microcatheter with the titanium needle in the metastasis compared to interventions with the 2D FLASH sequence (2.9 +/- 0.83 vs. 4.4 +/- 1.63). With 2D FLASH imaging, acquisition in a second plane was necessary in 78 instances (20% of acquired 2D sequences) to ensure adequate positioning of the device during the procedure. The artifact caused by the titanium needle was smaller with the 3D FLASH sequence. The conspicuity of liver metastases and morphology (liver edge and vessels) was acceptable with both sequences. The 3D FLASH sequence improved differentiation when two to four titanium needles were inserted, due to smaller susceptibility artifacts caused by the needles., Conclusion: 3D GRE imaging with the capability to perform multiplanar reconstruction (MPR) shortens the procedure by reducing the number of sequences needed. Improved visibility of the titanium needles allows more precise insertion of multiple needles into the metastasis., ((c) 2007 Wiley-Liss, Inc.)

Rationale: Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal (HPA) axis and immunity., Objectives: The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients., Methods: In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence. Nonalcoholic patients were included but only as a descriptive control. Perioperative intervention with low-dose ethanol (0.5 g/kg body weight per day), morphine (15 mug/kg body weight per hour), ketoconazole (200 mg four times daily), and placebo was started on the morning before surgery and continued for 3 d after surgery. Blood samples to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1, 3, and 7 after surgery., Measurements and Main Results: In long-term alcoholic patients, all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio. All interventions decreased the pneumonia rate from 39% to a median of 5.7% and shortened intensive care unit stay by 9 d (median) compared with the placebo-treated long-term alcoholic patients., Conclusions: Intervention at the level of the HPA axis altered the immune response to surgical stress. This resulted in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients.