Doctor's Orders-Why Radiologists Should Consider Adjusting Commercial Machine Learning Applications in Chest Radiography to Fit Their Specific Needs.

This retrospective study evaluated a commercial deep learning (DL) software for chest radiographs and explored its performance in different scenarios. A total of 477 patients (284 male, 193 female, mean age 61.4 (44.7-78.1) years) were included. For the reference standard, two radiologists performed independent readings on seven diseases, thus reporting 226 findings in 167 patients. An autonomous DL reading was performed separately and evaluated against the gold standard regarding accuracy, sensitivity and specificity using ROC analysis. The overall average AUC was 0.84 (95%-CI 0.76-0.92) with an optimized DL sensitivity of 85% and specificity of 75.4%. The best results were seen in pleural effusion with an AUC of 0.92 (0.885-0.955) and sensitivity and specificity of each 86.4%. The data also showed a significant influence of sex, age, and comorbidity on the level of agreement between gold standard and DL reading. About 40% of cases could be ruled out correctly when screening for only one specific disease with a sensitivity above 95% in the exploratory analysis. For the combined reading of all abnormalities at once, only marginal workload reduction could be achieved due to insufficient specificity. DL applications like this one bear the prospect of autonomous comprehensive reporting on chest radiographs but for now require human supervision. Radiologists need to consider possible bias in certain patient groups, e.g., elderly and women. By adjusting their threshold values, commercial DL applications could already be deployed for a variety of tasks, e.g., ruling out certain conditions in screening scenarios and offering high potential for workload reduction.

Is there a fast track ("Darmstrasse") for fluids in the small intestine? Evidence from magnetic resonance imaging.

BACKGROUND: The transit and distribution pattern of fluids in the small intestine is a key parameter for the dissolution and absorption of drugs. Although some information is known about the small intestinal water content after administration of fluid volumes and meals, the intestinal transit of orally ingested fluids and solutions has been barely investigated. The aim of this three-arm, cross-over, 9-subject human study was to investigate the transit of orally ingested water in the small intestine under fasting and postprandial conditions using MRI. To identify the ingested water, manganese gluconate, which can be identified with T1-weighted MRI sequences, was added as a marker. Using Horos (DICOM software), quantification of the distribution of Mn2+ ions in the gastrointestinal tract in fasted versus fed state (standard meal by FDA guidance and a light meal) was possible. The distribution and approximate wetted intestinal length was very similar in the fasting and postprandial states, suggesting rapid transport of water ingested after a meal through the chyme-filled small intestine in continuation of the "Magenstrasse" (stomach road). In some subjects, manganese gluconate reached deeper parts of the small intestine even more quickly in the postprandial state than in the fasting arm of the study. A deeper understanding of the behaviour of solutes in the gastrointestinal tract is fundamental to a mechanistic explanation for the kinetic interaction between food and drug intake (food effects).

Automated image quality assessment for selecting among multiple magnetic resonance image acquisitions in the German National Cohort study.

In magnetic resonance imaging (MRI), the perception of substandard image quality may prompt repetition of the respective image acquisition protocol. Subsequently selecting the preferred high-quality image data from a series of acquisitions can be challenging. An automated workflow may facilitate and improve this selection. We therefore aimed to investigate the applicability of an automated image quality assessment for the prediction of the subjectively preferred image acquisition. Our analysis included data from 11,347 participants with whole-body MRI examinations performed as part of the ongoing prospective multi-center German National Cohort (NAKO) study. Trained radiologic technologists repeated any of the twelve examination protocols due to induced setup errors and/or subjectively unsatisfactory image quality and chose a preferred acquisition from the resultant series. Up to 11 quantitative image quality parameters were automatically derived from all acquisitions. Regularized regression and standard estimates of diagnostic accuracy were calculated. Controlling for setup variations in 2342 series of two or more acquisitions, technologists preferred the repetition over the initial acquisition in 1116 of 1396 series in which the initial setup was retained (79.9%, range across protocols: 73-100%). Image quality parameters then commonly showed statistically significant differences between chosen and discarded acquisitions. In regularized regression across all protocols, 'structured noise maximum' was the strongest predictor for the technologists' choice, followed by 'N/2 ghosting average'. Combinations of the automatically derived parameters provided an area under the ROC curve between 0.51 and 0.74 for the prediction of the technologists' choice. It is concluded that automated image quality assessment can, despite considerable performance differences between protocols and anatomical regions, contribute substantially to identifying the subjective preference in a series of MRI acquisitions and thus provide effective decision support to readers.

The Effect of Cooling Fluid Composition on Ablation Size in Hepatic Laser Ablation: A Comparative Study in an Ex Vivo Bovine Setting.

PURPOSE: Hyperthermic ablation is a minimally invasive mode of tumour therapy which serves as a viable alternative to surgical intervention. However, one of the major drawbacks, besides the heat sink effect and the risk of damaging adjacent organs, is limited ablation size. The use of a cooling fluid during ablation has been shown to increase the ablation volume and decrease the carbonisation rate. The aim of this study was to investigate whether the composition of the cooling fluid has an effect on ablation size and carbonisation rate during hepatic laser ablation in an ex vivo bovine setting. METHOD: In this study bovine hepatic tissue was ablated in an ex vivo setting using an internally cooled laser applicator. A total of 45 tissue samples were assigned to three groups: 0.9% saline infusion (n = 15), distilled water infusion (n = 15) and a 50%/50% mixture of 0.9% saline and distilled water (n = 15). Ablation was conducted using a 1064 nm Nd:YAG laser at a wattage of 25 W and time interval of 10 min. The ablation volume and carbonisation rate were then measured and recorded through postprocedural MRI. One-way ANOVA and post-hoc testing were performed to assess the effect of the cooling fluid composition on the ablation volumes. RESULTS: We found that using a mixture of saline and distilled water as a cooling fluid during hyperthermic ablation resulted in a larger ablation volume (mean ± SD: 22.64 ± 0.99 cm3) when compared to saline infusion (21.08 ± 1.11 cm3) or distilled water infusion (20.92 ± 0.92 cm3). This difference was highly significant (p < 0.001). There was no significant difference in ablation size between the saline group and the distilled water group. The highest carbonisation rate occurred in the saline group (12/15), followed by the mixed infusion group (3/15) and the distilled water group (1/15). CONCLUSIONS: The results of this study suggest that cooling fluid composition during hepatic laser ablation affects ablation volume in an ex vivo bovine setting. There was no statistically significant difference when comparing ablation volumes during saline infusion and distilled water infusion, but the carbonisation rate was significantly higher when using saline. The combination of saline and distilled water in a 50%/50% mixture as cooling fluid appears to be an auspicious alternative, as ablation volumes created with it are larger when compared to saline and distilled water alone, while carbonisation rate remains low. This might improve patient outcome as well as patient eligibility for hyperthermic ablation.

Analysis of volume and topography of adipose tissue in the trunk: Results of MRI of 11,141 participants in the German National Cohort.

This research addresses the assessment of adipose tissue (AT) and spatial distribution of visceral (VAT) and subcutaneous fat (SAT) in the trunk from standardized magnetic resonance imaging at 3 T, thereby demonstrating the feasibility of deep learning (DL)-based image segmentation in a large population-based cohort in Germany (five sites). Volume and distribution of AT play an essential role in the pathogenesis of insulin resistance, a risk factor of developing metabolic/cardiovascular diseases. Cross-validated training of the DL-segmentation model led to a mean Dice similarity coefficient of >0.94, corresponding to a mean absolute volume deviation of about 22 ml. SAT is significantly increased in women compared to men, whereas VAT is increased in males. Spatial distribution shows age- and body mass index-related displacements. DL-based image segmentation provides robust and fast quantification of AT (≈15 s per dataset versus 3 to 4 hours for manual processing) and assessment of its spatial distribution from magnetic resonance images in large cohort studies.

Quantitative Diffusion-Weighted MRI of Neuroblastoma.

Neuroblastoma is the most common extracranial, malignant, solid tumor found in children. In more than one-third of cases, the tumor is in an advanced stage, with limited resectability. The treatment options include resection, with or without (neo-/) adjuvant therapy, and conservative therapy, the latter even with curative intent. Contrast-enhanced MRI is used for staging and therapy monitoring. Diffusion-weighted imaging (DWI) is often included. DWI allows for a calculation of the apparent diffusion coefficient (ADC) for quantitative assessment. Histological tumor characteristics can be derived from ADC maps. Monitoring the response to treatment is possible using ADC maps, with an increase in ADC values in cases of a response to therapy. Changes in the ADC value precede volume reduction. The usual criteria for determining the response to therapy can therefore be supplemented by ADC values. While these changes have been observed in neuroblastoma, early changes in the ADC value in response to therapy are less well described. In this study, we evaluated whether there is an early change in the ADC values in neuroblastoma under therapy; if this change depends on the form of therapy; and whether this change may serve as a prognostic marker. We retrospectively evaluated neuroblastoma cases treated in our institution between June 2007 and August 2014. The examinations were grouped as 'prestaging'; 'intermediate staging'; 'final staging'; and 'follow-up'. A classification of "progress", "stable disease", or "regress" was made. For the determination of ADC values, regions of interest were drawn along the borders of all tumor manifestations. To calculate ADC changes (∆ADC), the respective MRI of the prestaging was used as a reference point or, in the case of therapies that took place directly after previous therapies, the associated previous staging. In the follow-up examinations, the previous examination was used as a reference point. The ∆ADC were grouped into ∆ADCregress for regressive disease, ∆ADCstable for stable disease, and ∆ADC for progressive disease. In addition, examinations at 60 to 120 days from the baseline were grouped as er∆ADCregress, er∆ADCstable, and er∆ADCprogress. Any differences were tested for significance using the Mann-Whitney test (level of significance: p < 0.05). In total, 34 patients with 40 evaluable tumor manifestations and 121 diffusion-weighted MRI examinations were finally included. Twenty-seven patients had INSS stage IV neuroblastoma, and seven had INSS stage III neuroblastoma. A positive N-Myc expression was found in 11 tumor diseases, and 17 patients tested negative for N-Myc (with six cases having no information). 26 patients were assigned to the high-risk group according to INRG and eight patients to the intermediate-risk group. There was a significant difference in mean ADC values from the high-risk group compared to those from the intermediate-risk group, according to INRG. The differences between the mean ∆ADC values (absolute and percentage) according to the course of the disease were significant: between ∆ADCregress and ∆ADCstable, between ∆ADCprogress and ∆ADCstable, as well as between ∆ADCregress and ∆ADCprogress. The differences between the mean er∆ADC values (absolute and percentage) according to the course of the disease were significant: between er∆ADCregress and er∆ADCstable, as well as between er∆ADCregress and er∆ADCprogress. Forms of therapy, N-Myc status, and risk groups showed no further significant differences in mean ADC values and ∆ADC/er∆ADC. A clear connection between the ADC changes and the response to therapy could be demonstrated. This held true even within the first 120 days after the start of therapy: an increase in the ADC value corresponds to a probable response to therapy, while a decrease predicts progression. Minimal or no changes were seen in cases of stable disease.

Spacer-Supported Thermal Ablation to Prevent Carbonisation and Improve Ablation Size: A Proof of Concept Study.

Thermal ablation offers a minimally invasive alternative in the treatment of hepatic tumours. Several types of ablation are utilised with different methods and indications. However, to this day, ablation size remains limited due to the formation of a central non-conductive boundary layer. In thermal ablation, this boundary layer is formed by carbonisation. Our goal was to prevent or delay carbonisation, and subsequently increase ablation size. We used bovine liver to compare ablation diameter and volume, created by a stand-alone laser applicator, with those created when utilising a spacer between laser applicator and hepatic tissue. Two spacer variants were developed: one with a closed circulation of cooling fluid and one with an open circulation into hepatic tissue. We found that the presence of a spacer significantly increased ablation volume up to 75.3 cm3, an increase of a factor of 3.19 (closed spacer) and 3.02 (open spacer) when compared to the stand-alone applicator. Statistical significance between spacer variants was also present, with the closed spacer producing a significantly larger ablation volume (p < 0.001, MDiff = 3.053, 95% CI[1.612, 4.493]) and diameter (p < 0.001, MDiff = 4.467, 95% CI[2.648, 6.285]) than the open spacer. We conclude that the presence of a spacer has the potential to increase ablation size.

Trauma to the Eye: Diffusion Restriction on MRI as a Surrogate Marker for Blindness.

Traumatic optic nerve injury may lead to almost instantaneous blindness. We describe a case of sight loss after a perforating injury to the eye. The case is unusual in that the patient remained conscious and the trauma to the eye was isolated. A full ophthalmological examination was therefore possible within hours as well as early magnetic resonance imaging of the facial skull. High-quality T1-weighted, T2-weighted, and diffusion-weighted imaging could be acquired. The latter included apparent diffusion coefficient maps. There was a loss of the subarachnoid space of the optic nerve, fluid in the retrobulbar fat of the affected eye, and signal changes in the optic nerve. Previous work has been contradictory on the signal of the optic nerve on apparent diffusion coefficient maps in sight loss, with an increase seen by one group and a decrease seen by another. Signal loss on the apparent diffusion coefficient map was seen in the case described here. Signal loss on apparent diffusion coefficient maps may thus be used as a surrogate marker of sight loss in patients who are unconscious or otherwise unable to cooperate in ophthalmological exams.

Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI.

Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA methylation has received little attention. We investigated the association between white matter hyperintensity burden and DNA methylation in blood at ∼450 000 cytosine-phosphate-guanine (CpG) sites in 9732 middle-aged to older adults from 14 community-based studies. Single CpG and region-based association analyses were carried out. Functional annotation and integrative cross-omics analyses were performed to identify novel genes underlying the relationship between DNA methylation and white matter hyperintensities. We identified 12 single CpG and 46 region-based DNA methylation associations with white matter hyperintensity burden. Our top discovery single CpG, cg24202936 (P = 7.6 × 10-8), was associated with F2 expression in blood (P = 6.4 × 10-5) and co-localized with FOLH1 expression in brain (posterior probability = 0.75). Our top differentially methylated regions were in PRMT1 and in CCDC144NL-AS1, which were also represented in single CpG associations (cg17417856 and cg06809326, respectively). Through Mendelian randomization analyses cg06809326 was putatively associated with white matter hyperintensity burden (P = 0.03) and expression of CCDC144NL-AS1 possibly mediated this association. Differentially methylated region analysis, joint epigenetic association analysis and multi-omics co-localization analysis consistently identified a role of DNA methylation near SH3PXD2A, a locus previously identified in genome-wide association studies of white matter hyperintensities. Gene set enrichment analyses revealed functions of the identified DNA methylation loci in the blood-brain barrier and in the immune response. Integrative cross-omics analysis identified 19 key regulatory genes in two networks related to extracellular matrix organization, and lipid and lipoprotein metabolism. A drug-repositioning analysis indicated antihyperlipidaemic agents, more specifically peroxisome proliferator-activated receptor-alpha, as possible target drugs for white matter hyperintensities. Our epigenome-wide association study and integrative cross-omics analyses implicate novel genes influencing white matter hyperintensity burden, which converged on pathways related to the immune response and to a compromised blood-brain barrier possibly due to disrupted cell-cell and cell-extracellular matrix interactions. The results also suggest that antihyperlipidaemic therapy may contribute to lowering risk for white matter hyperintensities possibly through protection against blood-brain barrier disruption.

Do brachycephaly and nose size predict the severity of obstructive sleep apnea (OSA)? A sample-based geometric morphometric analysis of craniofacial variation in relation to OSA syndrome and the role of confounding factors.

Obstructive sleep apnea is a common disorder that leads to sleep fragmentation and is potentially bidirectionally related to a variety of comorbidities, including an increased risk of heart failure and stroke. It is often considered a consequence of anatomical abnormalities, especially in the head and neck, but its pathophysiology is likely to be multifactorial in origin. With geometric morphometrics, and a large sample of adults from the Study for Health in Pomerania, we explore the association of craniofacial morphology to the apnea-hypopnea index used as an estimate of obstructive sleep apnea severity. We show that craniofacial size and asymmetry, an aspect of morphological variation seldom analysed in obstructive sleep apnea research, are both uncorrelated to apnea-hypopnea index. In contrast, as in previous analyses, we find evidence that brachycephaly and larger nasal proportions might be associated to obstructive sleep apnea severity. However, this correlational signal is weak and completely disappears when age-related shape variation is statistically controlled for. Our findings suggest that previous work might need to be re-evaluated, and urge researchers to take into account the role of confounders to avoid potentially spurious findings in association studies.

Vitamin D deficit is associated with accelerated brain aging in the general population.

Vitamin D deficiency has been associated with reduced neurocognitive functioning and the neurodegenerative processes. However, existing evidence on brain structural correlates of vitamin D deficiency is controversial. We sought to investigate associations of vitamin D levels with imaging patterns of brain aging. In addition, we investigated whether low vitamin D levels were associated with gray matter volumes, whole brain volumes and hippocampus volumes. Structural MRI data and vitamin D levels were obtained in 1,865 subjects from the general population. Linear regressions were applied to investigate the association of vitamin D levels and vitamin D deficiency with imaging derived brain age, total brain, gray matter and hippocampal volumes. Different sets of covariates were included. Vitamin D deficiency was significantly associated with increased brain age. Also, linear vitamin D levels were significantly associated with total brain and gray matter volumes, while no significant association with hippocampal volume was found. Further interaction analyses showed that this association was only significant for male subjects. Our results support previous findings suggesting that vitamin D-deficient individuals have an accelerated brain aging. In addition, associations between vitamin D levels and total brain/ gray matter volumes suggest neuroprotective effects of vitamin D on the brain.

Epidemiological Factors Associated With Intraductal Papillary Mucinous Neoplasm of the Pancreas: A Dual Center Case-Control Study.

OBJECTIVE: The present study aimed to identify epidemiological factors associated with the development of intraductal papillary mucinous neoplasms (IPMN) of the pancreas comparing patients after IPMN resection with population-based controls. METHODS: Preoperative data of 811 patients undergoing pancreatic resection for IPMN were matched in a 1:1 ratio with a random sample of volunteers from the Study of Health in Pomerania, which showed no pancreatic cyst greater than 2 mm in magnetic resonance cholangiopancreaticography. RESULTS: A total of 811 controls with a mean age of 61.9 years (standard deviation, 8.4 years) were matched to cases with a mean age of 66.1 years (standard deviation, 9.3 years). A previous history of pancreatitis, endocrine pancreatic insufficiency was significantly more frequent in IPMN patients compared with controls (P = 0.001). Moreover, adjusted data revealed that urogenital cancer (P = 0.034), colorectal cancer (P = 0.021), as well as first-degree family history of colorectal cancer (P = 0.001) were significantly more frequent in IPMN patients. CONCLUSIONS: A history of urogenital and colorectal cancer often coincides with IPMN, which have an indication for surgery and are associated with preoperative episodes of pancreatitis and with endocrine insufficiency. Prospective studies are needed to investigate the role of these factors in IPMN development.

Insulin-Like Growth Factor, Inflammation, and MRI Markers of Alzheimer's Disease in Predominantly Middle-Aged Adults.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer's disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults. OBJECTIVE: To investigate the association of serum IGF-1 and IGF binding protein 3 (IGFBP-3) concentrations with MRI markers of Alzheimer's disease in predominantly middle-aged adults, and further assess moderation by chronic inflammation. METHODS: We included participants from the Framingham Heart Study (n = 1,852, mean age 46±8, 46% men) and the Study of Health in Pomerania (n = 674, mean age 50±13, 42% men) with available serum IGF-1, IFGBP-3, as well as brain MRI. IGF-1 and IFGBP-3 were related to MRI outcomes (i.e., total brain, cortical gray matter, white matter, white matter hyperintensities (WMH), and hippocampal volumes) using multivariable regression models adjusting for potential confounders. Subgroup analyses by C-reactive protein (CRP) concentrations were also performed. Cohort-specific summary statistics were meta-analyzed using random-effects models and corrected for multiple comparisons. RESULTS: Meta-analysis results revealed that higher IGF-1 concentrations were associated with lower WMH (estimate [ß] [95% CI], -0.05 [-0.09, -0.02], p = 0.006) and larger hippocampal volumes (0.07 [0.02, 0.12], p = 0.01), independent of vascular risk factors. These associations occurred predominantly in individuals with CRP concentrations < 75th percentile. We did not observe associations between IGFBP-3 and MRI outcomes. CONCLUSION: Our findings suggest that IGF-1-related signaling may be implicated in brain health as early as midlife.

Whole-Body Magnetic Resonance Imaging in the Large Population-Based German National Cohort Study: Predictive Capability of Automated Image Quality Assessment for Protocol Repetitions.

BACKGROUND: Reproducible image quality is of high relevance for large cohort studies and can be challenging for magnetic resonance imaging (MRI). Automated image quality assessment may contribute to conducting radiologic studies effectively. PURPOSE: The aims of this study were to assess protocol repetition frequency in population-based whole-body MRI along with its effect on examination time and to examine the applicability of automated image quality assessment for predicting decision-making regarding repeated acquisitions. MATERIALS AND METHODS: All participants enrolled in the prospective, multicenter German National Cohort (NAKO) study who underwent whole-body MRI at 1 of 5 sites from 2014 to 2016 were included in this analysis (n = 11,347). A standardized examination program of 12 protocols was used. Acquisitions were carried out by certified radiologic technologists, who were authorized to repeat protocols based on their visual perception of image quality. Eleven image quality parameters were derived fully automatically from the acquired images, and their discrimination ability regarding baseline acquisitions and repetitions was tested. RESULTS: At least 1 protocol was repeated in 12% (n = 1359) of participants, and more than 1 protocol in 1.6% (n = 181). The repetition frequency differed across protocols (P < 0.001), imaging sites (P < 0.001), and over the study period (P < 0.001). The mean total scan time was 62.6 minutes in participants without and 67.4 minutes in participants with protocol repetitions (mean difference, 4.8 minutes; 95% confidence interval, 4.5-5.2 minutes). Ten of the automatically derived image quality parameters were individually retrospectively predictive for the repetition of particular protocols; for instance, "signal-to-noise ratio" alone provided an area under the curve of 0.65 (P < 0.001) for repetition of the Cardio Cine SSFP SAX protocol. Combinations generally improved prediction ability, as exemplified by "image sharpness" plus "foreground ratio" yielding an area under the curve of 0.89 (P < 0.001) for repetition of the Neuro T1w 3D MPRAGE protocol, versus 0.85 (P < 0.001) and 0.68 (P < 0.001) as individual parameters. CONCLUSIONS: Magnetic resonance imaging protocol repetitions were necessary in approximately 12% of scans even in the highly standardized setting of a large cohort study. Automated image quality assessment shows predictive value for the technologists' decision to perform protocol repetitions and has the potential to improve imaging efficiency.

Clinical and neurophysiological patterns of impairments to emotion attention and empathy in multiple sclerosis.

Patients suffering from multiple sclerosis experience various cognitive and affective impairments, resulting in a negative impact on social behavior and personal independence to differing degrees. According to these often clinically subtle but conflicting cognitive-affective impairments, recordings of these socially relevant issues are still of demand to stratifying clinical and social support in a sophisticated way. Therefore, we studied specific cognitive and affective capacities in eleven patients with a predominant relapsing-remitting type of multiple sclerosis by applying paradigms of event-related potentials and a well-selected neuropsychological test protocol. Thus far, distinct cognitive disturbances of executive and attentional domains and the Wechsler Memory Test's four memory indices were found in multiple sclerosis patients. Concerning affective domains, patients showed discrete impairments of affect discrimination and affected naming as proved by specific testing (Tuebinger Affect Battery). Neurophysiologically, event-related potentials recordings in multiple sclerosis patients, were associated with decreased implicit emotion processing to cues of different emotion arousal at the early processing stage depending on attentional capacities and alterations of implicit emotion modulation at late processing stages. These clinical neurophysiological and neuropsychological data were correlated in part to quantitative magnetic resonance imaging brain lesions. Summarizing our data, our data indicate certain neurocognitive and neuroaffective dysfunctions in patients with multiple sclerosis, thus highlighting the validity of sensitive recording of less apparent neurologic disturbances in multiple sclerosis for optimizing the individual care management in patients.

Circulating Metabolome and White Matter Hyperintensities in Women and Men.

BACKGROUND: White matter hyperintensities (WMH), identified on T2-weighted magnetic resonance images of the human brain as areas of enhanced brightness, are a major risk factor of stroke, dementia, and death. There are no large-scale studies testing associations between WMH and circulating metabolites. METHODS: We studied up to 9290 individuals (50.7% female, average age 61 years) from 15 populations of 8 community-based cohorts. WMH volume was quantified from T2-weighted or fluid-attenuated inversion recovery images or as hypointensities on T1-weighted images. Circulating metabolomic measures were assessed with mass spectrometry and nuclear magnetic resonance spectroscopy. Associations between WMH and metabolomic measures were tested by fitting linear regression models in the pooled sample and in sex-stratified and statin treatment-stratified subsamples. Our basic models were adjusted for age, sex, age×sex, and technical covariates, and our fully adjusted models were also adjusted for statin treatment, hypertension, type 2 diabetes, smoking, body mass index, and estimated glomerular filtration rate. Population-specific results were meta-analyzed using the fixed-effect inverse variance-weighted method. Associations with false discovery rate (FDR)-adjusted P values (PFDR)<0.05 were considered significant. RESULTS: In the meta-analysis of results from the basic models, we identified 30 metabolomic measures associated with WMH (PFDR<0.05), 7 of which remained significant in the fully adjusted models. The most significant association was with higher level of hydroxyphenylpyruvate in men (PFDR.full.adj=1.40×10-7) and in both the pooled sample (PFDR.full.adj=1.66×10-4) and statin-untreated (PFDR.full.adj=1.65×10-6) subsample. In men, hydroxyphenylpyruvate explained 3% to 14% of variance in WMH. In men and the pooled sample, WMH were also associated with lower levels of lysophosphatidylcholines and hydroxysphingomyelins and a larger diameter of low-density lipoprotein particles, likely arising from higher triglyceride to total lipids and lower cholesteryl ester to total lipids ratios within these particles. In women, the only significant association was with higher level of glucuronate (PFDR=0.047). CONCLUSIONS: Circulating metabolomic measures, including multiple lipid measures (eg, lysophosphatidylcholines, hydroxysphingomyelins, low-density lipoprotein size and composition) and nonlipid metabolites (eg, hydroxyphenylpyruvate, glucuronate), associate with WMH in a general population of middle-aged and older adults. Some metabolomic measures show marked sex specificities and explain a sizable proportion of WMH variance.

Subcortical shape alterations in major depressive disorder: Findings from the ENIGMA major depressive disorder working group.

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = -0.164 to -0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = -0.173 to -0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

Association Between Obstructive Sleep Apnea and Brain White Matter Hyperintensities in a Population-Based Cohort in Germany.

Importance: Underlying pathomechanisms of brain white matter hyperintensities (WMHs), commonly observed in older individuals and significantly associated with Alzheimer disease and brain aging, have not yet been fully elucidated. One potential contributing factor to WMH burden is chronic obstructive sleep apnea (OSA), a disorder highly prevalent in the general population with readily available treatment options. Objective: To investigate potential associations between OSA and WMH burden. Design, Setting, and Participants: Analyses were conducted in 529 study participants of the Study of Health in Pomerania-Trend baseline (SHIP-Trend-0) study with complete WMH, OSA, and important clinical data available. SHIP-Trend-0 is a general population-based, cross-sectional, observational study to facilitate the investigation of a large spectrum of common risk factors, subclinical disorders, and clinical diseases and their relationships among each other with patient recruitment from Western Pomerania, Germany, starting on September 1, 2008, with data collected until December 31, 2012. Data analysis was performed from February 1, 2019, to January 31, 2021. Exposures: The apnea-hypopnea index (AHI) and oxygen desaturation index (ODI) were assessed during a single-night, laboratory-based polysomnography measurement. Main Outcomes and Measures: The primary outcome was WMH data automatically segmented from 1.5-T magnetic resonance images. Results: Of 529 study participants (mean [SD] age, 52.15 [13.58] years; 282 female [53%]), a total of 209 (40%) or 102 (19%) individuals were diagnosed with OSA according to AHI or ODI criteria (mean [SD] AHI, 7.98 [12.55] events per hour; mean [SD] ODI, 3.75 [8.43] events per hour). Both AHI (ß = 0.024; 95% CI, 0.011-0.037; P <.001) and ODI (ß = 0.033; 95% CI, 0.014-0.051; P <. 001) were significantly associated with brain WMH volumes. These associations remained even in the presence of additional vascular, metabolic, and lifestyle WMH risk factors. Region-specific WMH analyses found the strongest associations between periventricular frontal WMH volumes and both AHI (ß = 0.0275; 95% CI, 0.013-0.042, P < .001) and ODI (ß = 0.0381; 95% CI, 0.016-0.060, P < .001) as well as periventricular dorsal WMH volumes and AHI (ß = 0.0165; 95% CI, 0.004-0.029, P = .008). Conclusions and Relevance: This study found significant associations between OSA and brain WMHs, indicating a novel, potentially treatable WMH pathomechanism.

Retrospective Cohort Study of Frequency and Patterns of Orbital Injuries on Whole-Body CT with Maxillofacial Multi-Slice CT.

Background: High-impact trauma frequently leads to injuries of the orbit, but literature focusing on the viscerocranium rather than the neurocranium is underrepresented. Methods: Retrospective cohort study (2006-2014) at an urban level 1 trauma center assessing the frequency and typical patterns of orbital injuries on whole-body computed tomography (WBCT) with maxillofacial multi-slice CT (MSCT) after severe trauma. (1) Screening of consecutive WBCT cases for dedicated maxillofacial MSCT. (2) Examination by two independent experts' radiologists for (peri-/)orbital injuries. (3) Case review for trauma mechanisms. Results: 1061 WBCT were included revealing 250 (23.6%) patients with orbital injuries. Less than one-quarter (23.3%) of patients showed osseous and 9.5% showed soft tissue injuries. Combined osseous and soft tissue lesions were present in 39.2% of orbital injuries, isolated soft tissue injuries were rare. Single- or two-wall fractures of the orbit were prevalent, and the orbital floor was affected in 67% of fractures. Dislocated extraocular muscles (44.6%), deformation of the ocular globe (23.8%), and elongation of the optic nerve (12.9%) were the most frequently soft tissue findings. Vascular trauma was suspected in 15.8% of patients. Conclusions: Orbital trauma was confirmed in 23.6% of cases with suspected facial injuries after severe trauma. Concomitant soft tissue injuries should be excluded explicitly in cases with orbital fractures to prevent loss of vision or ocular motility.