Forensic age assessment by 3.0 T MRI of the wrist: adaption of the Vieth classification.

OBJECTIVES: In order to find a reliable method to correctly assess majority in both sexes by MRI, a study was conducted to evaluate the applicability of the recently presented Vieth classification in wrist MRI, after it had originally been proposed for knee MRI. METHODS: After receiving a positive vote by the ethics committee, the left-hand wrists of 347 male and 348 female volunteers of German nationality in the age bracket 12-24 years were scanned. Before conducting the prospective, cross-sectional examinations, an informed consent was obtained from each volunteer. A 3.0 T MRI scanner was used, acquiring a T1 turbo spin-echo sequence (TSE) and a T2 TSE sequence with fat suppression by spectral presaturation with inversion recovery (SPIR). The images were assessed by applying the Vieth classification. Minimum, maximum, mean ± standard deviation, and median with lower and upper quartiles were defined. Intra- and interobserver agreements were determined by calculating the kappa coefficients. Differences between the sexes were analyzed using the Mann-Whitney U test. RESULTS: By applying the unmodified Vieth classification with corresponding schematics, it was possible to assess majority in both sexes via the epiphyseal-diaphyseal fusion of the distal radius and in males also via the epiphyseal-diaphyseal fusion of the distal ulna. The Mann-Whitney U test implied significant sex-related differences for all stages. For both epiphyses, the intra- and interobserver agreement levels were very good (κ > 0.8). CONCLUSION: If confirmed by further studies, it would be possible to determine the completion of the 18th year of life in both sexes by 3.0 T MRI of the wrist and using the Vieth classification. KEY POINTS: • The Vieth classification allows determining majority in males and females alike based on the distal radius' epiphysis by 3.0 T MRI of the wrist. • The Vieth classification also allows determining majority in males based on the distal ulna's epiphysis by 3.0 T MRI of the wrist, but not in females. • The presented data can be deemed referential within certain discussed boundaries.

Prefrontal gray matter volume mediates genetic risks for obesity.

Genetic and neuroimaging research has identified neurobiological correlates of obesity. However, evidence for an integrated model of genetic risk and brain structural alterations in the pathophysiology of obesity is still absent. Here we investigated the relationship between polygenic risk for obesity, gray matter structure and body mass index (BMI) by the use of univariate and multivariate analyses in two large, independent cohorts (n=330 and n=347). Higher BMI and higher polygenic risk for obesity were significantly associated with medial prefrontal gray matter decrease, and prefrontal gray matter was further shown to significantly mediate the effect of polygenic risk for obesity on BMI in both samples. Building on this, the successful individualized prediction of BMI by means of multivariate pattern classification algorithms trained on whole-brain imaging data and external validations in the second cohort points to potential clinical applications of this imaging trait marker.

Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group.

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Low rates of recanalization for wide-necked aneurysms treated with stenting after balloon-assisted coiling: combination of techniques delivers stable and improved results during follow-up.

PURPOSE: In the treatment of wide-necked aneurysms, stenting may be required after balloon-assisted coiling (BAC) for reconstructing the lumen/flow of the parent artery in cases of coil herniation. The potential benefits and complications of both techniques remain unclear when used together. Our aim was to assess the safety and long-term angiographic outcomes of stenting after BAC. METHODS: Retrospective review of 87 unruptured wide necked aneurysms (in 80 patients) treated with BAC and requiring stent placement at the final stage of the procedure due to coil prolapse. Aneurysm characteristics, technical issues, clinical records, and MR results were assessed. Post-treatment and follow-up angiograms were evaluated by two independent reviewers and categorized as "stable," "further thrombosis," or "recanalization." RESULTS: The mean maximum diameter was 9.1 ± 4.7 mm and aspect ratio 1.20 ± 0.47. Complete and near-complete initial occlusion were observed in 53 (60.9%) and 28 (32.2%) of all treated aneurysms, respectively. Angiographic follow-up (80 aneurysms; mean, 34.68 ± 25.26 months) revealed stability and further thrombosis in 92.4% (74/80). Recanalization was observed in six cases (7.5%, 6/83), four of which were retreated. No significantly different outcomes were found in terms of aneurysm size (p = 0.641). Transient and reversible procedure-related complications occurred in eight (9.2%), minor permanent deficits in 2.3%, and major deficits, including death, in four cases (4.6%). CONCLUSION: Our results suggest that treatment of wide-necked aneuryms with stent placement after BAC yields low recanalization rates and enhanced angiographic outcomes in long-term follow-up.

[Impact of anamnestic information and neurological deficits on the detection rate of secondary headaches]. / Einfluss von Anamnese und neurologischer Untersuchung auf die Detektionsrate sekundärer Kopfschmerzursachen.

PURPOSE: Headaches are a very common symptom and imaging is important to rule out symptomatic causes. For clinical differentiation between primary and secondary headaches an exact anamnesis and neurological examination are important. The aim of this study is therefore to identify anamnestic and neurological information that is associated with secondary headaches. Moreover, this study gives an overview of the causes and differential diagnoses of secondary headaches. METHODS: We performed a retrospective analysis of 239 patients ≥18 years with headaches who had undergone computed tomography or magnetic resonance imaging. The impact of basic characteristics such as age and gender as well as anamnestic (pain intensity, thromboembolic risk profile) and clinical information (neurological deficit, papilledema, reduced vigilance) was tested by χ2 test at the significance level p < 0.05. RESULTS: In all, 27 of the included patients (11.3%) showed intracranial pathologies that required treatment. The most frequent pathologies were intracranial hypertension (9 patients), cerebral mass lesions (7 patients) and thrombosis of the cranial sinus/veins (3 patients). There was a significant association of a pathologic imaging finding and neurological deficits (p = 0.001) and a papilledema (p < 0.001). Reduced vigilance, pain intensity and thromboembolic risk factors as well as age and gender showed no significant association. CONCLUSIONS: A neurological deficit and especially papilledema are hints towards secondary headaches and should result in computed tomography or magnetic resonance imaging. Other factors such as reduced vigilance, pain intensity, age and gender have no relevant impact on the occurrence of intracranial pathologies.

Effects of electroconvulsive therapy on amygdala function in major depression - a longitudinal functional magnetic resonance imaging study.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, little is known regarding brain functional processes mediating ECT effects. METHOD: In a non-randomized prospective study, functional magnetic resonance imaging data during the automatic processing of subliminally presented emotional faces were obtained twice, about 6 weeks apart, in patients with major depressive disorder (MDD) before and after treatment with ECT (ECT, n = 24). Additionally, a control sample of MDD patients treated solely with pharmacotherapy (MED, n = 23) and a healthy control sample (HC, n = 22) were obtained. RESULTS: Before therapy, both patient groups equally showed elevated amygdala reactivity to sad faces compared with HC. After treatment, a decrease in amygdala activity to negative stimuli was discerned in both patient samples indicating a normalization of amygdala function, suggesting mechanisms potentially unspecific for ECT. Moreover, a decrease in amygdala activity to sad faces was associated with symptomatic improvements in the ECT sample (r spearman = -0.48, p = 0.044), and by tendency also for the MED sample (r spearman = -0.38, p = 0.098). However, we did not find any significant association between pre-treatment amygdala function to emotional stimuli and individual symptom improvement, neither for the ECT sample, nor for the MED sample. CONCLUSIONS: In sum, the present study provides first results regarding functional changes in emotion processing due to ECT treatment using a longitudinal design, thus validating and extending our knowledge gained from previous treatment studies. A limitation was that ECT patients received concurrent medication treatment.

Digital mammography screening: sensitivity of the programme dependent on breast density.

OBJECTIVES: To analyse the impact of breast density on the sensitivity of a population-based digital mammography screening programme (SP) as key evaluation parameter. METHODS: 25,576 examinations were prospectively stratified from ACR category 1 to 4 for increments of 25 % density during independent double reading. SP was calculated as number of screen-detected cancers divided by the sum of screen-detected plus interval cancers (24-months period) per ACR category, related to the first reading (a), second reading (b) and highest stratification if discrepant (c). Chi-square tests were used for comparison. RESULTS: Overall sensitivity of the programme was 79.9 %. SP in ACR 4 (a: 50 %, b: 50 %, c: 50 %) was significantly lower than in ACR 3 (a: 72.9 %, b: 79.4 %, c: 80.7 %, p < 0.001), ACR 2 (a: 83.9 %, b: 85.7 %, c: 83.2 %, p < 0.001) and ACR 1 (a: 100 %, b: 88.8 %, c: 100 %; p < 0.001). Frequencies of ACR 4 were a: 5.0 %, b: 4.3 %, c: 6.9 %. CONCLUSION: Digital mammography screening with independent double reading leads to a high overall SP. In the small group of women with breast density classified as ACR 4 SP is significantly reduced compared to all other ACR categories. KEY POINTS: • Overall sensitivity of a population-based digital mammography screening programme (SP) was 79.9 %. • In women with ACR 1, 2, or 3, SP ranged between 72.9 %-100 %. • ACR 4 was rare in participants (<7 %) and SP was only 50 %. • SP in ACR 4 differed significantly from ACR 3 (p < 0.001).

The impact of lesion location on dysphagia incidence, pattern and complications in acute stroke. Part 2: Oropharyngeal residue, swallow and cough response, and pneumonia.

BACKGROUND AND PURPOSE: Dysphagia is a well-known complication of acute stroke. Given the complexity of cerebral swallowing control it is still difficult to predict which patients are likely to develop swallowing dysfunction based on their neuroimaging. In Part 2 of a comprehensive voxel-based imaging study, whether the location of a stroke lesion can be correlated with further dysfunctional swallowing patterns, pulmonary protective reflexes and pneumonia was evaluated. METHODS: In all, 200 acute stroke cases were investigated applying flexible endoscopic evaluation of swallowing within 96 h from admission. Lesions were mapped using patients' computed tomography/magnetic resonance images and these were registered to a standard space. The percentage of lesioned volume of 137 anatomically defined brain regions was determined on a voxel basis (FSL5.0). Region-specific odds ratios (ORs) were calculated with respect to the presence of oropharyngeal residue, delayed swallow response, insufficient cough reflex and occurrence of pneumonia during hospital stay. Colour-coded lesion location maps of brain regions with significant ORs were created (P < 0.05). RESULTS: Lesion maps for residue and impaired swallow response depicted parietal-temporal areas of the right hemisphere. Limbic structures in the right hemisphere and sensory regions on the left were associated with cough reflex disturbance. There was no overlap of lesion maps for impaired swallow response and insufficient cough reflex or pneumonia, but substantial overlap between the last two conditions. CONCLUSIONS: This study gives new insights on the cortical representation of single components of swallowing and airway protection behaviours. The lesion model may help to risk-stratify patients for dysphagia and pneumonia based on their brain scan.

Magnetic resonance imaging-based evaluation of ossification of the medial clavicular epiphysis in forensic age assessment.

Evaluation of the degree of ossification of the medial clavicular epiphysis plays a crucial role in determining with an adequate degree of probability whether legally relevant age boundaries after the age of 17 have been crossed. In view of the need to avoid unnecessary radiation exposure, establishing non-X-ray methods for investigating the clavicle has long been a key objective in forensic age assessment research. Based on magnetic resonance imaging examinations in a large sample of healthy subjects, the current study for the first time presents statistical measures which allow inferences to be drawn for forensic age assessment in both sexes. We undertook a prospective study of a reference sample of 334 female and 335 male German volunteers aged from 12 to 24 using a 3-T MRI scanner. A 3D FFE (fast field echo) T1-weighted sequence with fat saturation was acquired. To stage ossification of the medial clavicular epiphysis, we used the clavicular ossification staging systems described by Schmeling et al. and Kellinghaus et al. Ossification stage IIIc offers a means in both sexes of demonstrating that the age of 18 has been attained prior to complete ossification of the epiphyseal plate. In both sexes, if a subject has reached ossification stage IV, it can be stated that he or she has attained the age of 21. Magnetic resonance imaging is a valid diagnostic procedure for determining the ossification stage of the medial clavicular epiphysis.

Magnetic resonance imaging of the distal radial epiphysis: a new criterion of maturity for determining whether the age of 18 has been completed?

To improve the accuracy of forensic age estimation where there is no legal basis for carrying out x-ray examinations, it would be useful to establish non-x-ray imaging techniques. The objective of this study was to provide reference data for the magnetic resonance imaging-based evaluation of the ossification stage of the distal radius. Furthermore, we tested a new criterion of the maturity of the distal radial epiphysis for determining whether an individual has completed the age of 18. We investigated 668 MRI scans of the distal radial epiphysis from 333 female and 335 male subjects ranging in age from 12 to 24. To determine the ossification stage, we used the clavicular ossification staging systems described by Schmeling et al. and Kellinghaus et al. Ossification stage IV as described by Schmeling et al. was divided into two sub-stages, IVa and IVb, depending on whether or not it was possible to identify a triple-banded meta-epiphyseal zone of calcification. All study subjects were able to be assigned to an ossification stage without ambiguity. We present statistics relating to the distribution of ossification stages divided by sex. The age of the youngest female subject assessed as ossification stage IVb was 16.8, the age of the youngest male subject 18.6. The youngest age at which female subjects were assessed as ossification stage V was 22.3; for male subjects it was 23.1. Further independent studies should be carried out to determine whether ossification stage IVb can indeed be used to reliably determine whether a male subject has completed the age of 18.

Differing brain structural correlates of familial and environmental risk for major depressive disorder revealed by a combined VBM/pattern recognition approach.

BACKGROUND: Neuroimaging traits of either familial or environmental risk for major depressive disorder (MDD) have been interpreted as possibly useful vulnerability markers. However, the simultaneous occurrence of familial and environmental risk might prove to be a major obstacle in the attempt of recent studies to confine the precise impact of each of these conditions on brain structure. Moreover, the exclusive use of group-level analyses does not permit prediction of individual illness risk which would be the basic requirement for the clinical application of imaging vulnerability markers. Hence, we aimed to distinguish between brain structural characteristics of familial predisposition and environmental stress by using both group- and individual-level analyses. METHOD: We investigated grey matter alterations between 20 healthy control subjects (HC) and 20 MDD patients; 16 healthy first-degree relatives of MDD patients (FH+) and 20 healthy subjects exposed to former childhood maltreatment (CM+) by using a combined VBM/pattern recognition approach. RESULTS: We found similar grey matter reductions in the insula and the orbitofrontal cortex in patients and FH+ subjects and in the hippocampus in patients and CM+ subjects. No direct overlap in grey matter alterations was found between FH+ and CM+ subjects. Pattern classification successfully detected subjects at risk for the disease even by strictly focusing on morphological traits of MDD. CONCLUSIONS: Familial and environmental risk factors for MDD are associated with differing morphometric anomalies. Pattern recognition might be a promising instrument in the search for and future application of vulnerability markers for MDD.

Multimodal imaging of a tescalcin (TESC)-regulating polymorphism (rs7294919)-specific effects on hippocampal gray matter structure.

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

Abdominal and pelvic CT: is positive enteric contrast still necessary? Results of a retrospective observational study.

PURPOSE: Evaluation of diagnostic accuracy of abdominal CT depending on the type of enteric contrast agent. METHODS AND MATERIALS: Multislice CTs of 2,008 patients with different types of oral preparation (positive with barium, n = 576; neutral with water, n = 716; and no enteric contrast, n = 716) were retrospectively evaluated by two radiologists including delineation of intestinal segments and influence on diagnosis and diagnostic reliability exerted by the enteric contrast, using a three-point scale. Furthermore, diagnostic reliability of the delineation of selected enteric pathologies was noted. CT data were assigned into groups: oncology, inflammation, vascular, pathology, trauma and gastrointestinal pathology. RESULTS: Delineation of the bowel was clearly practicable across all segments irrespective of the type of enteric contrast, though a slight impairment was observed without enteric contrast. Although delineation of intestinal pathologies was mostly classified "clearly delimitable" more difficulties occurred without oral contrast (neutral/positive/no contrast, 0.8 %/3.8 %/6.5 %). Compared to examinations without enteric contrast, there was a significant improvement in diagnosis that was even increased regarding the reader's diagnostic reliability. Positive opacification impaired detection of mucosal enhancement or intestinal bleeding. CONCLUSION: Water can replace positive enteric contrast agents in abdominal CTs. However, selected clinical questions require individual enteric contrast preparations. Pathology detection is noticeably impaired without any enteric contrast.

The impact of lesion location on dysphagia incidence, pattern and complications in acute stroke. Part 1: dysphagia incidence, severity and aspiration.

BACKGROUND AND PURPOSE: Although early identification of patients at risk for dysphagia is crucial in acute stroke care, predicting whether a particular patient is likely to have swallowing problems based on the brain scan is difficult because a comprehensive model of swallowing control is missing. In this study whether stroke location is associated with dysphagia incidence, severity and the occurrence of penetration or aspiration was systematically evaluated relying on a voxel-based imaging analysis approach. METHODS: Two hundred acute stroke patients were investigated applying fiberoptic endoscopic evaluation of swallowing within 96 h from admission. Lesion masks were obtained from each patient's brain scan and registered to standard space. The percentage of lesioned volume of 137 atlas-based brain regions was determined in each case. Region-specific odds ratios were afterwards calculated with respect to presence of dysphagia, its severity and occurrence of penetration or aspiration. RESULTS: In all, 165 patients were diagnosed with dysphagia, 80 of whom had severe swallow impairment. For each investigated item there were significant differences of regional percentage infarction in distinct brain areas between affected patients and those who did not present with that specific dysfunction. In particular, right hemispheric lesions of the pre- and post-central gyri, opercular region, supramarginal gyrus and respective subcortical white matter tracts were related to dysphagia, with post-central lesions being especially associated with severe swallowing impairment. CONCLUSIONS: Distinct brain lesion locations are related to the incidence, severity and pattern of swallowing dysfunction.

Comparison of manual and semi-automatic measuring techniques in MSCT scans of patients with lymphoma: a multicentre study.

OBJECTIVES: Multicentre evaluation of the precision of semi-automatic 2D/3D measurements in comparison to manual, linear measurements of lymph nodes regarding their inter-observer variability in multi-slice CT (MSCT) of patients with lymphoma. METHODS: MSCT data of 63 patients were interpreted before and after chemotherapy by one/two radiologists in five university hospitals. In 307 lymph nodes, short (SAD)/long (LAD) axis diameter and WHO area were determined manually and semi-automatically. Volume was solely calculated semi-automatically. To determine the precision of the individual parameters, a mean was calculated for every lymph node/parameter. Deviation of the measured parameters from this mean was evaluated separately. Statistical analysis entailed intraclass correlation coefficients (ICC) and Kruskal-Wallis tests. RESULTS: Median relative deviations of semi-automatic parameters were smaller than deviations of manually assessed parameters, e.g. semi-automatic SAD 5.3 vs. manual 6.5 %. Median variations among different study sites were smaller if the measurement was conducted semi-automatically, e. g. manual LAD 5.7/4.2 % vs. semi-automatic 3.4/3.4 %. Semi-automatic volumetry was superior to the other parameters (2.8 %). CONCLUSIONS: Semi-automatic determination of different lymph node parameters is (compared to manually assessed parameters) associated with a slightly greater precision and a marginally lower inter-observer variability. These results are with regard to the increasing mobility of patients among different medical centres and in relation to the quality management of multicentre trials of importance. KEY POINTS: • In a multicentre setting, semi-automatic measurements are more accurate than manual assessments. • Lymph node volumetry outperforms all other semi-automatically and manually performed measurements. • Use of semi-automatic lymph node analyses can reduce the inter-observer variability.

[Imaging diagnostics of bone sarcomas]. / Bildgebende Diagnostik der Knochensarkome.

BACKGROUND: Bone tumors and especially bone sarcomas are rare lesions of the skeletal system in comparison to the much more frequently occurring bone metastases. Despite the relative rarity they are important differential diagnoses of bone lesions. OBJECTIVE: The aim of this article is to give the reader an insight into the fundamentals of the primary imaging of bone sarcomas and to illustrate this with the help of two examples (e.g. osteosarcoma and chondrosarcoma). RESULTS: The foundation of the imaging of bone sarcomas is the radiograph in two planes. This method delivers important information on bone tumors. This information should be analyzed with the help of the Lodwick classification, the configuration of periosteal reactions and a possible reaction of the cortex. A possible tumor matrix and the localization within the skeleton or within long bones also provide important information for differential diagnostic delimitation. Magnetic resonance imaging (MRI) with specific adapted bone tumor sequences allows an exact local staging of a bone sarcoma. In addition to local imaging a compartmental MRI which illustrates the entire extent of tumor-bearing bone and the adjacent joints should be performed to rule out possible skip lesions. The most common distant metastases of osteosarcoma and chondrosarcoma occur in the lungs; therefore, a computed tomography (CT) of the chest is part of staging. Other imaging methods, such as CT of the tumor, positron emission tomography CT (PET-CT), bone scan and whole body MRI supplement the imaging depending on tumor type.

Intratumoral heterogeneity after targeted therapy in murine cancer models with differing degrees of malignancy.

INTRODUCTION: Conventional morphologic and volumetric assessment of treatment response is not suitable for adequately assessing responses to targeted cancer therapy. The aim of this study was to evaluate changes in tumor composition after targeted therapy in murine models of breast cancer with differing degrees of malignancy via non-invasive magnetic resonance imaging (MRI). MATERIALS AND METHODS: Mice bearing highly malignant 4T1 tumors or low malignant 67NR tumors were treated with either a combination of two immune checkpoint inhibitors (ICI, anti-PD1 and anti-CTLA-4) or the multi-tyrosine kinase inhibitor sorafenib, following experiments with macrophage-depleting clodronate-loaded liposomes and vessel-stabilizing angiopoietin-1. Mice were imaged on a 9.4 T small animal MRI system with a multiparametric (mp) protocol, comprising T1 and T2 mapping and diffusion-weighted imaging. Tumors were analyzed ex vivo with histology. RESULTS AND DISCUSSIONS: All treatments led to an increase in non-viable areas, but therapy-induced intratumoral changes differed between the two tumor models and the different targeted treatments. While ICI treatment led to intratumoral hemorrhage, sorafenib treatment mainly induced intratumoral necrosis. Treated 4T1 tumors showed increasing and extensive areas of necrosis, in comparison to 67NR tumors with only small, but also increasing, necrotic areas. After either of the applied treatments, intratumoral heterogeneity, was increased in both tumor models, and confirmed ex vivo by histology. Apparent diffusion coefficient with subsequent histogram analysis proved to be the most sensitive MRI sequence. In conclusion, mp MRI enables to assess dedicated therapy-related intratumoral changes and may serve as a biomarker for treatment response assessment.

Sex-specifics of ECT outcome.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. METHODS: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). RESULTS: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. CONCLUSION: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

Neuropeptide S receptor gene -- converging evidence for a role in panic disorder.

Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn¹°7Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case-control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli.

Diagnostic and radiological management of cystic pancreatic lesions: important features for radiologists.

Cystic pancreatic neoplasms are often an incidental finding, the frequency of which is increasing. The understanding of such lesions has increased in recent years, but the numerous types of lesions involved can hinder differential diagnosis. They include, in particular, intraductal papillary mucinous neoplasms (IPMN), serous cystic neoplasms (SCN), and mucinous cystic neoplasms (MCN). Knowledge of their histological and radiological structure, as well as distribution in terms of localization, age, and sex, helps to differentiate such tumours from common pancreatic pseudocysts. Several types of cystic pancreatic neoplasms can undergo malignant transformation and, therefore, require differentiated radiological management. This review aims to develop a broader understanding of the pathological and radiological characteristics of cystic pancreatic neoplasms, and provide a guideline for everyday practice based on current concepts in the radiological management of the given lesions.