Individual Variability in Functional Organization of the Human and Monkey Auditory Cortex.

Accumulating evidence shows that auditory cortex (AC) of humans, and other primates, is involved in more complex cognitive processes than feature segregation only, which are shaped by experience-dependent plasticity and thus likely show substantial individual variability. However, thus far, individual variability of ACs has been considered a methodological impediment rather than a phenomenon of theoretical importance. Here, we examined the variability of ACs using intrinsic functional connectivity patterns in humans and macaques. Our results demonstrate that in humans, interindividual variability is greater near the nonprimary than primary ACs, indicating that variability dramatically increases across the processing hierarchy. ACs are also more variable than comparable visual areas and show higher variability in the left than in the right hemisphere, which may be related to the left lateralization of auditory-related functions such as language. Intriguingly, remarkably similar modality differences and lateralization of variability were also observed in macaques. These connectivity-based findings are consistent with a confirmatory task-based functional magnetic resonance imaging analysis. The quantification of variability in auditory function, and the similar findings in both humans and macaques, will have strong implications for understanding the evolution of advanced auditory functions in humans.

Correction: Individual-specific functional connectivity markers track dimensional and categorical features of psychotic illness.

The original version of this article omitted the author "Roscoe O. Brady Jr." from the "Psychotic Disorders Division, McLean Hospital, Harvard Medical School, Belmont, MA, USA" and the "Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA". This has been corrected in both the PDF and HTML versions of the article.

Individual-specific functional connectivity markers track dimensional and categorical features of psychotic illness.

Neuroimaging studies of psychotic disorders have demonstrated abnormalities in structural and functional connectivity involving widespread brain networks. However, these group-level observations have failed to yield any biomarkers that can provide confirmatory evidence of a patient's current symptoms, predict future symptoms, or predict a treatment response. Lack of precision in both neuroanatomical and clinical boundaries have likely contributed to the inability of even well-powered studies to resolve these key relationships. Here, we employed a novel approach to defining individual-specific functional connectivity in 158 patients diagnosed with schizophrenia (n = 49), schizoaffective disorder (n = 37), or bipolar disorder with psychosis (n = 72), and identified neuroimaging features that track psychotic symptoms in a dimension- or disorder-specific fashion. Using individually specified functional connectivity, we were able to estimate positive, negative, and manic symptoms that showed correlations ranging from r = 0.35 to r = 0.51 with the observed symptom scores. Comparing optimized estimation models among schizophrenia spectrum patients, positive and negative symptoms were associated with largely non-overlapping sets of cortical connections. Comparing between schizophrenia spectrum and bipolar disorder patients, the models for positive symptoms were largely non-overlapping between the two disorder classes. Finally, models derived using conventional region definition strategies performed at chance levels for most symptom domains. Individual-specific functional connectivity analyses revealed important new distinctions among cortical circuits responsible for the positive and negative symptoms, as well as key new information about how circuits underlying symptom expressions may vary depending on the underlying etiology and illness syndrome from which they manifest.

Hepatic fat is superior to BMI, visceral and pancreatic fat as a potential risk biomarker for neurodegenerative disease.

OBJECTIVES: Prior studies relating body mass index (BMI) to brain volumes suggest an overall inverse association. However, BMI might not be an ideal marker, as it disregards different fat compartments, which carry different metabolic risks. Therefore, we analyzed MR-based fat depots and their association with gray matter (GM) volumes of brain structures, which show volumetric changes in neurodegenerative diseases. METHODS: Warp-based automated brain segmentation of 3D FLAIR sequences was obtained in a population-based study cohort. Associations of temporal lobe, cingulate gyrus, and hippocampus GM volume with BMI and MR-based quantification of visceral adipose tissue (VAT), as well as hepatic and pancreatic proton density fat fraction (PDFFhepatic and PDFFpanc, respectively), were assessed by linear regression. RESULTS: In a sample of 152 women (age 56.2 ± 9.0 years) and 199 men (age 56.1 ± 9.1 years), we observed a significant inverse association of PDFFhepatic and cingulate gyrus volume (p < 0.05) as well as of PDFFhepatic and hippocampus volume (p < 0.05), when adjusting for age and sex. This inverse association was further enhanced for cingulate gyrus volume after additionally adjusting for hypertension, smoking, BMI, LDL, and total cholesterol (p < 0.01) and also alcohol (p < 0.01). No significant association was observed between PDFFhepatic and temporal lobe and between temporal lobe, cingulate gyrus, or hippocampus volume and BMI, VAT, and PDFFpanc. CONCLUSIONS: We observed a significant inverse, independent association of cingulate gyrus and hippocampus GM volume with hepatic fat, but not with other obesity measures. Increased hepatic fat could therefore serve as a marker of high-risk fat distribution. KEY POINTS: • Obesity is associated with neurodegenerative processes. • In a population-based study cohort, hepatic fat was superior to BMI and visceral and pancreatic fat as a risk biomarker for decreased brain volume of cingulate gyrus and hippocampus. • Increased hepatic fat could serve as a marker of high-risk fat distribution.

Increased cerebral microbleeds and cortical superficial siderosis in pediatric patients with Down syndrome.

BACKGROUND: Patients with Down syndrome carry a third copy of the amyloid precursor protein gene, which is localized on chromosome 21. Consequently, these patients are prone to develop early-onset Alzheimer disease and cerebral amyloid angiopathy. Post-mortem studies suggest increased amyloid deposition to be already detectable in children with Down syndrome. The aim of our study was to evaluate if amyloid-related changes in pediatric Down syndrome patients can be detected in vivo using MRI biomarkers of cerebral microbleeds and cortical superficial siderosis. MATERIALS AND METHODS: This retrospective study included 12 patients with Down syndrome (mean age = 5.0 years) and 12 age-matched control subjects (mean age = 4.8 years). Frequency and location of microbleeds and siderosis were assessed on blood-sensitive MRI sequences in a consensus reading by two radiologists applying a modified Microbleed Anatomical Rating Scale. RESULTS: Down syndrome patients showed a significantly higher mean microbleeds count and likelihood of siderosis than age-matched controls. Across groups, the highest microbleeds count was found in lobar regions (gray and white matter of frontal, parietal, temporal, and occipital lobes, and the insula), while fewer microbleeds were located in subcortical and infratentorial regions. The number of microbleeds increased over time in all three Down syndrome patients with a follow-up exam. CONCLUSION: In vivo MRI biomarkers can support the diagnosis of early-onset cerebral amyloid angiopathy, which might already be present in pediatric Down syndrome patients. This might contribute to clinical decision-making and potentially to the development of therapeutic and prophylactic approaches, as cerebral amyloid angiopathy increases the risk for intracranial hemorrhage and may be associated with increased risk of developing Alzheimer disease.

T1-MPRAGE and T2-FLAIR segmentation of cortical and subcortical brain regions-an MRI evaluation study.

PURPOSE: Development of a warp-based automated brain segmentation approach of 3D fluid-attenuated inversion recovery (FLAIR) images and comparison to 3D T1-based segmentation. METHODS: 3D FLAIR and 3D T1-weighted sequences of 30 healthy subjects (mean age 29.9 ± 8.3 years, 8 female) were acquired on the same 3T MR scanner. Warp-based segmentation was applied for volumetry of total gray matter (GM), white matter (WM), and 116 atlas regions. Segmentation results of both sequences were compared using Pearson correlation (r). RESULTS: Correlation of GM segmentation results based on FLAIR and T1 was overall good for cortical structures (mean r across all cortical structures = 0.76). Comparatively weaker results were found in the occipital lobe (r = 0.77), central region (mean r = 0.58), basal ganglia (mean r = 0.59), thalamus (r = 0.30), and cerebellum (r = 0.73). FLAIR segmentation underestimated volume of the central region compared to T1, but showed a better anatomic concordance with the occipital lobe on visual review and subcortical structures, when also compared to manual segmentation. Visual analysis of FLAIR-based WM segmentation revealed frequent misclassification of regions of high signal intensity as GM. CONCLUSION: Warp-based FLAIR segmentation yields comparable results to T1 segmentation for most cortical GM structures and may provide anatomically more congruent segmentation of subcortical GM structures. Selected cortical regions, especially the central region and total WM, seem to be underestimated on FLAIR segmentation.

CT attenuation of liver metastases before targeted therapy is a prognostic factor of overall survival in colorectal cancer patients. Results from the randomised, open-label FIRE-3/AIO KRK0306 trial.

OBJECTIVES: To assess the prognostic value of pre-therapeutic computed tomography (CT) attenuation of liver metastases for overall survival (OS) in metastatic colorectal cancer (mCRC). METHODS: In the open-label, randomised, prospective phase-III FIRE-3 trial, patients with histologically confirmed mCRC received fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) with either cetuximab or bevacizumab. Participating patients gave written informed consent prior to study entry. In CT at baseline (portal venous phase, slice thickness ≤5 mm), mean attenuation [Hounsfield units (HU)] of liver metastases was retrospectively assessed by semi-automated volumetry. Its prognostic influence on OS was analysed in Kaplan-Meier-analysis and Cox proportional hazard regression and an optimal threshold was determined. RESULTS: In FIRE-3, 592 patients were enrolled between 2007 and 2012. Among the 347 patients eligible for liver volumetry, median baseline CT attenuation of liver metastases was 59.67 HU [interquartile range (IQR), 49.13, 68.85]. Increased attenuation was associated with longer OS {per 10 HU: hazard ratio (HR), 0.85 [95% confidence interval (CI), 0.78, 0.93], p < 0.001}. The optimised threshold (≥61.62 HU) was a strong predictor for increased OS [median, 21.3 vs 30.6 months; HR, 0.61 (95% CI, 0.47, 0.80), p < 0.001]. Multivariate regression controlling for correlated and further prognostic factors confirmed this [HR, 0.60 (95% CI, 0.45, 0.81), p = 0.001]. Furthermore, mean attenuation ≥61.62 HU was significantly associated with increased early tumour shrinkage (p = 0.002) and increased depth of response (p = 0.012). CONCLUSIONS: Increased mean baseline CT attenuation of liver metastases may identify mCRC patients with prolonged OS and better tumour response. KEY POINTS: • In colorectal cancer, increased attenuation of liver metastases in baseline computed tomography is a prognostic factor for prolonged OS (p < 0.001). • A threshold of ≥61.62 HU was determined as optimal cut-off to identify patients with prolonged OS (p < 0.001), early tumour shrinkage (p = 0.002) and increased depth of response (p = 0.012).

Predictive value of coronary computed tomography angiography in asymptomatic individuals with diabetes mellitus: Systematic review and meta-analysis.

BACKGROUND: Coronary CT angiography (CTA) is generally not established as a screening tool for asymptomatic individuals. However, it is controversial whether this test may have a role for screening asymptomatic individuals with diabetes mellitus (DM) due to the high prevalence of asymptomatic coronary artery disease (CAD) in this subgroup. METHODS: We searched PubMed and EMBASE through May 2017 for studies that reported on the association between findings at coronary CTA and future cardiac events in asymptomatic individuals with DM. Summary hazard ratios for the presence of obstructive CAD (≥50% stenosis), presence of non-obstructive plaque (<50% stenosis), segment involvement score, and segment stenosis score were derived using a random effects regression model. I2 was calculated to quantify between-study heterogeneity and causing factors were identified using meta-regression. RESULTS: A total of 10 studies reporting on 5012 individuals with DM (median age: 62.3 years, median proportion of women: 40.5%) were included in the analysis. The presence of obstructive CAD on coronary CTA (vs. non-obstructive or no CAD) was associated with a significantly elevated risk for adverse events (summary HR: 4.07, 95% CI: 2.30 to 7.21). The estimated summary HR for non-obstructive plaque (vs. no CAD) was 2.17 (95% CI: 1.11 to 4.25). The pooled HRs per unit for segment stenosis score and segment involvement score were 1.44 (95% CI: 0.98 to 2.12), and 1.73 (95% CI: 1.07 to 2.80) respectively. On meta-regression analysis, we observed a trend towards a higher risk estimate in studies with a higher proportion of females (p = 0.1063). CONCLUSION: The presence and extent of CAD on coronary CTA are strong, independent predictors of cardiovascular events in asymptomatic individuals with DM despite heterogeneity between studies in endpoints, study population and length of follow-up.

Structured Reporting of CT Angiography Runoff Examinations of the Lower Extremities.

OBJECTIVES: The aim was to evaluate the effect of structured reporting of computed tomography angiography (CTA) runoff studies on clarity, completeness, clinical relevance, usefulness of the radiology reports, further testing, and therapy in patients with known or suspected peripheral arterial disease. METHODS: Conventional reports (CRs) and structured reports (SRs) were generated for 52 patients who had been examined with a CTA runoff examination of the lower extremities. The sample size was based on power calculations with a power of 95% and a significance level of .007 (adjusted for multiple testing). CRs were dictated in a free text form; SRs contained a consistent ordering of observations with standardised subheadings. CRs were compared with SRs. Two vascular medicine specialists and two vascular surgeons rated the reports regarding their satisfaction with clarity, completeness, clinical relevance, and usefulness as well as overall satisfaction. Additionally, they made hypothetical decisions on further testing and therapy. Median ratings were compared using the Wilcoxon signed rank test and generalised linear mixed effects models. RESULTS: SRs received higher ratings for satisfaction with clarity (median rating 9.0 vs. 7.0, p < .0001) and completeness (median rating 9.0 vs. 7.5, p < .0001) and were judged to be of greater clinical relevance (median rating 9.0 vs. 8.0, p < .0001) and usefulness (median rating 9.0 vs. 8.0, p < .0001). Overall satisfaction was also higher for SRs (median rating 9.0 vs. 7.0, p < .0001) than CRs. There were no significant differences in further testing or therapy. CONCLUSION: Referring clinicians perceive SRs of CTA runoff examinations of the lower extremities as offering superior clarity, completeness, clinical relevance, and usefulness than CRs. Structured reporting does not appear to alter further testing or therapy in patients with known or suspected peripheral arterial disease.

Structured reporting adds clinical value in primary CT staging of diffuse large B-cell lymphoma.

OBJECTIVES: To evaluate whether template-based structured reports (SRs) add clinical value to primary CT staging in patients with diffuse large B-cell lymphoma (DLBCL) compared to free-text reports (FTRs). METHODS: In this two-centre study SRs and FTRs were acquired for 16 CT examinations. Thirty-two reports were independently scored by four haematologists using a questionnaire addressing completeness of information, structure, guidance for patient management and overall quality. The questionnaire included yes-no, 10-point Likert scale and 5-point scale questions. Altogether 128 completed questionnaires were evaluated. Non-parametric Wilcoxon signed-rank test and McNemar's test were used for statistical analysis. RESULTS: SRs contained information on affected organs more often than FTRs (95 % vs. 66 %). More SRs commented on extranodal involvement (91 % vs. 62 %). Sufficient information for Ann-Arbor classification was included in more SRs (89 % vs. 64 %). Information extraction was quicker from SRs (median rating on 10-point Likert scale=9 vs. 6; 7-10 vs. 4-8 interquartile range). SRs had better comprehensibility (9 vs. 7; 8-10 vs. 5-8). Contribution of SRs to clinical decision-making was higher (9 vs. 6; 6-10 vs. 3-8). SRs were of higher quality (p < 0.001). All haematologists preferred SRs over FTRs. CONCLUSIONS: Structured reporting of CT examinations for primary staging in patients with DLBCL adds clinical value compared to FTRs by increasing completeness of reports, facilitating information extraction and improving patient management. KEY POINTS: • Structured reporting in CT helps clinicians to assess patients with lymphoma. • This two-centre study showed that structured reporting improves information content and extraction. • Patient management may be improved by structured reporting. • Clinicians preferred structured reports over free-text reports.

Improved Detection of Foreign Bodies on Radiographs Using X-ray Dark-Field and Phase-Contrast Imaging.

PURPOSE: The aim of this study was to investigate whether the detection of foreign bodies can be improved using dark-field and phase-contrast radiography compared with conventional (transmission) radiographs. MATERIALS AND METHODS: Experiments were performed using ex vivo pig paws, which were prepared with differently sized foreign bodies of metal, wood, and glass (n = 10 each). Paws without foreign bodies served as controls (n = 30). All images were acquired using an experimental grating-based large object radiography system. Five blinded readers (second- to fourth-year radiology residents) were asked to assess the presence or absence of any foreign body. Sensitivity and specificity for the detection of metal, wood, glass, and any foreign body were calculated and compared using McNemar test and generalized linear mixed models. RESULTS: Sensitivity for the detection of metal foreign bodies was 100% for all readers and image combinations. The sensitivity for the detection of wooden foreign bodies increased from 2% for transmission images to 78% when dark-field images were added (P < 0.0001). For glass foreign bodies, sensitivity increased from 84% for transmission images to 96% when adding phase-contrast images (P = 0.041). Sensitivity for the detection of any foreign body was 91% when transmission, dark-field, and phase-contrast images were viewed simultaneously, compared with 62% for transmission images alone (P < 0.0001). Specificity was 99% to 100% across all readers and radiography modalities. CONCLUSIONS: Adding dark-field images substantially improves the detection of wooden foreign bodies compared with the analysis of conventional (transmission) radiographs alone. Detection of glass foreign bodies was moderately improved when adding phase-contrast images.

Structured reports of videofluoroscopic swallowing studies have the potential to improve overall report quality compared to free text reports.

PURPOSE: To compare free text (FTR) and structured reports (SR) of videofluoroscopic swallowing studies (VFSS) and evaluate satisfaction of referring otolaryngologists and speech therapists. MATERIALS AND METHODS: Both standard FTR and SR of 26 patients with VFSS were acquired. A dedicated template focusing on oropharyngeal phases was created for SR using online software with clickable decision-trees and concomitant generation of semantically structured reports. All reports were evaluated regarding overall quality and content, information extraction and clinical decision support (10-point Likert scale (0 = I completely disagree, 10 = I completely agree)). RESULTS: Two otorhinolaryngologists and two speech therapists evaluated FTR and SR. SR received better ratings than FTR in all items. SR were perceived to contain more details on the swallowing phases (median rating: 10 vs. 5; P < 0.001), penetration and aspiration (10 vs. 5; P < 0.001) and facilitated information extraction compared to FTR (10 vs. 4; P < 0.001). Overall quality was rated significantly higher in SR than FTR (P < 0.001). CONCLUSION: SR of VFSS provide more detailed information and facilitate information extraction. SR better assist in clinical decision-making, might enhance the quality of the report and, thus, are recommended for the evaluation of VFSS. KEY POINTS: • Structured reports on videofluoroscopic exams of deglutition lead to improved report quality. • Information extraction is facilitated when using structured reports based on decision trees. • Template-based reports add more value to clinical decision-making than free text reports. • Structured reports receive better ratings by speech therapists and otolaryngologists. • Structured reports on videofluoroscopic exams may improve the comparability between exams.

Evaluation of Visualization Using a 50/50 (Contrast Media/Glucose 5% Solution) Technique for Radioembolization as an Alternative to a Standard Sandwich Technique.

BACKGROUND: Radioembolization (RE) with 90yttrium (90Y) resin microspheres generally employs a sandwich technique with separate sequential administration of contrast medium (CM), followed by vehicle (e.g., glucose 5% [G5] solution), then 90Y resin microspheres (in G5), then G5, and then CM again to avoid contact of CM and microspheres under fluoroscopic guidance. This study evaluates the visualization quality and safety of a modified sandwich technique with a 50/50-mixture of CM (Imeron 300) and G5 for administration of 90Y resin microspheres. MATERIALS AND METHODS: A retrospective analysis of 81 RE procedures in patients with primary or secondary liver tumors was performed. The quality of angiographic visualization of the hepatic vessels was assessed before the first injection and immediately before the whole dose has been injected. Visualization and flow rate were graded on a 5-point scale: 1 = very good to 5 = not visible/no antegrade flow. Univariate logistic regression models and multiple linear regression models were used to evaluate the prognostic variables associated with visualization and flow scores. RESULTS: Visualization quality was inversely related to flow rate, the lower the flow rate the better the grade of the visualization. Visualization quality was also inversely related to body-mass-index (BMI). Performing RE with the 50/50-CM/G5 mixture resulted in a mean injection time for 1 GBq of 15 min. No clinically significant adverse events, including radiation-induced liver disease were reported. CONCLUSION: RE with a 50/50-mixture of CM and G5 for administration of 90Y resin microspheres in a modified sandwich technique is a safe administration alternative and provides good visualization of hepatic vessels, which is inversely dependent on flow rate and BMI. Injection time was reduced compared with our experience with the standard sandwich technique.

Structured reporting of CT examinations in acute pulmonary embolism.

OBJECTIVES: To evaluate the effect of structured reporting of CT pulmonary angiography (CTPA) studies on the content, clarity and clinical usefulness of radiology reports in acute pulmonary embolism (PE). METHODS: Conventional and structured reports were generated for 41 patients with a CTPA positive for acute PE. Conventional reports were dictated in a free-text form using speech recognition; structured reports contained a consistent ordering of observations with standardized subheadings. Conventional reports were compared to standardized structured reports. Two general internists and two pulmonologists rated their satisfaction with the clarity and content of the report and its clinical usefulness and hypothetically assigned the patients to a suitable disposition and therapy. RESULTS: Overall, structured reports received higher ratings for content (median rating 10.0 vs. 8.5, p < 0.0001) and clarity (median rating 10.0 vs. 8.0). The increase in satisfaction with clarity was significant for both subgroups (p < 0.0001), while the increase in satisfaction with content was significant for pulmonologists only (p < 0.0001). The clinical utility of radiology reports improved with structured reporting overall (p = 0.004) and for pulmonologists (p = 0.0005). There were no significant differences in the patient disposition or therapy. CONCLUSION: Referring clinicians perceive structured CTPA reports as superior in clarity. Pulmonologists also appreciate structured reports as providing better content and clinical utility. Structured reporting does not appear to alter patients' management in acute PE.

Content Themes of Alcohol Advertising in U.S. Television-Latent Class Analysis.

BACKGROUND: There is little alcohol research that reports on the thematic contents of contemporary alcohol advertisements in U.S. television. Studies of alcohol ads from 2 decades ago did not identify "Partying" as a social theme. Aim of this study was to describe and classify alcohol advertisements aired in national television in terms of contents, airing times, and channel placements and to identify different marketing strategies of alcohol brands. METHODS: Content analysis of all ads from the top 20 U.S. beer and spirit brands aired between July 2009 and June 2011. These were 581 unique alcohol ads accounting for 272,828 (78%) national television airings. Ads were coded according to predefined definitions of 13 content areas. A latent class analysis (LCA) was conducted to define content cluster themes and determine alcoholic brands that were more likely to exploit these themes. RESULTS: About half of the advertisements (46%) were aired between 3 am and 8 pm, and the majority were placed either in Entertainment (40%) and Sports (38%) channels. Beer ads comprised 64% of the sample, with significant variation in airing times and channels between types of products and brands. LCA revealed 5 content classes that exploited the "Partying," "Quality," "Sports," "Manly," and "Relax" themes. The partying class, indicative of ad messages surrounding partying, love, and sex, was the dominant theme comprising 42% of all advertisements. Ads for alcopops, flavored spirits, and liqueur were more likely to belong to the party class, but there were also some beer brands (Corona, Heineken) where more than 67% of ads exploited this theme. CONCLUSIONS: This is the first analysis to identify a partying theme to contemporary alcohol advertising. Future analyses can now determine whether exposure to that or other themes predicts alcohol misuse among youth audiences.