Altered white matter microstructure is associated with social cognition and psychotic symptoms in 22q11.2 microdeletion syndrome.

22q11.2 Microdeletion Syndrome (22q11DS) is a highly penetrant genetic mutation associated with a significantly increased risk for psychosis. Aberrant neurodevelopment may lead to inappropriate neural circuit formation and cerebral dysconnectivity in 22q11DS, which may contribute to symptom development. Here we examined: (1) differences between 22q11DS participants and typically developing controls in diffusion tensor imaging (DTI) measures within white matter tracts; (2) whether there is an altered age-related trajectory of white matter pathways in 22q11DS; and (3) relationships between DTI measures, social cognition task performance, and positive symptoms of psychosis in 22q11DS and typically developing controls. Sixty-four direction diffusion weighted imaging data were acquired on 65 participants (36 22q11DS, 29 controls). We examined differences between 22q11DS vs. controls in measures of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), using both a voxel-based and region of interest approach. Social cognition domains assessed were: Theory of Mind and emotion recognition. Positive symptoms were assessed using the Structured Interview for Prodromal Syndromes. Compared to typically developing controls, 22q11DS participants showed significantly lower AD and RD in multiple white matter tracts, with effects of greatest magnitude for AD in the superior longitudinal fasciculus. Additionally, 22q11DS participants failed to show typical age-associated changes in FA and RD in the left inferior longitudinal fasciculus. Higher AD in the left inferior fronto-occipital fasciculus (IFO) and left uncinate fasciculus was associated with better social cognition in 22q11DS and controls. In contrast, greater severity of positive symptoms was associated with lower AD in bilateral regions of the IFO in 22q11DS. White matter microstructure in tracts relevant to social cognition is disrupted in 22q11DS, and may contribute to psychosis risk

A Cross-Sectional, Multi-Site Study of T1 Weighted Magnetic Resonance Image Properties

Cross sectional Magnetic Resonance Imaging (MRI) studies of the human brain have shown age related changes in morphometric measures as well as signal properties like tissue contrast. Greater access to open data sets and an emphasis on multicenter studies make repeatability of measures important. This study takes a novel dataset and MRI from the IXI open dataset to examine age related changes in MRI signal properties across sites. We processed T1 weighted MRIs of 1131 subjects from 3 sites using established tissue segmentation tools and region of interest sampling techniques to get regional and global estimates of signal intensity and volume. Signal intensity estimates were used to calculate gray-white contrast values. We created multiple linear regression models of the age related changes in gray-white contrast, within tissue coefficient of variation (CV), and tissue volume while controlling for the effects of gender and site. In addition we compared the contrast results computed using our method to the recent methods provided with FreeSurfer. Signal intensity decreased with age in two sites while increasing with age in the third. Gray-white contrast showed a decline with age in most regions across all sites. CV increased with age across all regions, sites and tissue types. GM and WM volume decreases with age globally and regionally while CSF volume increased with age. The three methods show strong proportional bias and poor agreement. It is problematic to make inferences about MRI signal intensity without first normalizing the result. Measures of contrast and CV are both normalized views of signal intensity and both show similar if inverse relationships with age. Volume changes seen here are in agreement with previously published results, but the rates differ by site. Normalizing volume measurements by inter-cranial volume removes the site-specific rate differences. While the gray-white contrast calculation methods show strong correlation, the estimates are not comparable. Age related MRI signal property changes exist and may affect morphometric measurements. The public health relevance of this research relates to the possibility that MRI contrast may be a biomarker for use in diagnosing neurodegenerative diseases like Alzheimer’s that affect elderly populations allowing earlier detection and treatment

Quantitative measurement of blood flow in paediatric brain tumours. A comparative study of dynamic susceptibility contrast and multi-timepoint arterial spin-labelled MRI

OBJECTIVE: Arterial spin-labelling (ASL) MRI uses intrinsic blood water to quantify the cerebral blood flow (CBF), removing the need for the injection of a gadolinium-based contrast agent used for conventional perfusion imaging such as dynamic susceptibility contrast (DSC). Owing to the non-invasive nature of the technique, ASL is an attractive option for use in paediatric patients. This work compared DSC and multi-timepoint ASL measures of CBF in paediatric brain tumours. METHODS: Patients (n = 23; 20 low-grade tumours and 3 high-grade tumours) had DSC and multi-timepoint ASL with and without vascular crushers (VC). VC removes the contribution from larger vessel blood flow. Mean perfusion metrics were extracted from control and T(1)-enhanced tumour regions of interest (ROIs): arterial arrival time (AAT) and CBF from the ASL images with and without VC, relative cerebral blood flow (rCBF), relative cerebral blood volume, delay time (DT) and mean transit time (MTT) from the DSC images. RESULTS: Significant correlations existed for: AAT and DT (r = 0.77, p = 0.0002) and CBF and rCBF (r = 0.56, p = 0.02) in control ROIs for ASL-noVC. No significant correlations existed between DSC and ASL measures in the tumour region. Significant differences between control and tumour ROI were found for MTT (p < 0.001) and rCBF (p < 0.005) measures. CONCLUSION: Significant correlations between ASL-noVC and DSC measures in the normal brain suggest that DSC is most sensitive to macrovascular blood flow. The absence of significant correlations within the tumour ROI suggests that ASL is sensitive to different physiological mechanisms compared with DSC measures. ADVANCES IN KNOWLEDGE: ASL provides information which is comparable with that of DSC in healthy tissues, but appears to reflect a different physiology in tumour tissues

Statistical Evaluations of the Reproducibility and Reliability of 3-Tesla High Resolution Magnetization Transfer Brain Images: A Pilot Study on Healthy Subjects

Magnetization transfer imaging (MT) may have considerable promise for early detection and monitoring of subtle brain changes before they are apparent on conventional magnetic resonance images. At 3 Tesla (T), MT affords higher resolution and increased tissue contrast associated with macromolecules. The reliability and reproducibility of a new high-resolution MT strategy were assessed in brain images acquired from 9 healthy subjects. Repeated measures were taken for 12 brain regions of interest (ROIs): genu, splenium, and the left and right hemispheres of the hippocampus, caudate, putamen, thalamus, and cerebral white matter. Spearman's correlation coefficient, coefficient of variation, and intraclass correlation coefficient (ICC) were computed. Multivariate mixed-effects regression models were used to fit the mean ROI values and to test the significance of the effects due to region, subject, observer, time, and manual repetition. A sensitivity analysis of various model specifications and the corresponding ICCs was conducted. Our statistical methods may be generalized to many similar evaluative studies of the reliability and reproducibility of various imaging modalities

On the Distribution of Salient Objects in Web Images and its Influence on Salient Object Detection

It has become apparent that a Gaussian center bias can serve as an important prior for visual saliency detection, which has been demonstrated for predicting human eye fixations and salient object detection. Tseng et al. have shown that the photographer's tendency to place interesting objects in the center is a likely cause for the center bias of eye fixations. We investigate the influence of the photographer's center bias on salient object detection, extending our previous work. We show that the centroid locations of salient objects in photographs of Achanta and Liu's data set in fact correlate strongly with a Gaussian model. This is an important insight, because it provides an empirical motivation and justification for the integration of such a center bias in salient object detection algorithms and helps to understand why Gaussian models are so effective. To assess the influence of the center bias on salient object detection, we integrate an explicit Gaussian center bias model into two state-of-the-art salient object detection algorithms. This way, first, we quantify the influence of the Gaussian center bias on pixel- and segment-based salient object detection. Second, we improve the performance in terms of F1 score, Fb score, area under the recall-precision curve, area under the receiver operating characteristic curve, and hit-rate on the well-known data set by Achanta and Liu. Third, by debiasing Cheng et al.'s region contrast model, we exemplarily demonstrate that implicit center biases are partially responsible for the outstanding performance of state-of-the-art algorithms. Last but not least, as a result of debiasing Cheng et al.'s algorithm, we introduce a non-biased salient object detection method, which is of interest for applications in which the image data is not likely to have a photographer's center bias (e.g., image data of surveillance cameras or autonomous robots)

A method for determining venous contribution to BOLD contrast sensory activation

While BOLD contrast reflects haemodynamic changes within capillaries serving neural tissue, it also has a venous component. Studies that have determined the relation of large blood vessels to the activation map indicate that veins are the source of the largest response, and the most delayed in time. It would be informative if the location of these large veins could be extracted from the properties of the functional responses, since vessels are not visible in BOLD contrast images. The present study describes a method for investigating whether measures taken from the functional response can reliably predict vein location, or at least be useful in down-weighting the venous contribution to the activation response, and illustrates this method using data from one subject. We combined fMRI at 3 Tesla with high-resolution anatomical imaging and MR venography to test whether the intrinsic properties of activation time courses corresponded to tissue type. Measures were taken from a gamma fit to the functional response. Mean magnitude showed a significant effect of tissue type (P veins ≈ grey matter > white matter. Mean delays displayed the same ranking across tissue types (P grey matter. However, measures for all tissue types were distributed across an overlapping range. A logistic regression model correctly discriminated 72% of the veins from grey matter in the absence of independent information of macroscopic vessels (ROC=0.72). Whilst tissue classification was not perfect for this subject, weighting the T contrast by the predicted probabilities materially reduced the venous component to the activation map

Altered hippocampal function in major depression despite intact structure and resting perfusion

Background: Hippocampal volume reductions in major depression have been frequently reported. However, evidence for functional abnormalities in the same region in depression has been less clear. We investigated hippocampal function in depression using functional magnetic resonance imaging (fMRI) and neuropsychological tasks tapping spatial memory function, with complementing measures of hippocampal volume and resting blood flow to aid interpretation. Method: A total of 20 patients with major depressive disorder (MDD) and a matched group of 20 healthy individuals participated. Participants underwent multimodal magnetic resonance imaging (MRI): fMRI during a spatial memory task, and structural MRI and resting blood flow measurements of the hippocampal region using arterial spin labelling. An offline battery of neuropsychological tests, including several measures of spatial memory, was also completed. Results: The fMRI analysis showed significant group differences in bilateral anterior regions of the hippocampus. While control participants showed task-dependent differences in blood oxygen level-dependent (BOLD) signal, depressed patients did not. No group differences were detected with regard to hippocampal volume or resting blood flow. Patients showed reduced performance in several offline neuropsychological measures. All group differences were independent of differences in hippocampal volume and hippocampal blood flow. Conclusions: Functional abnormalities of the hippocampus can be observed in patients with MDD even when the volume and resting perfusion in the same region appear normal. This suggests that changes in hippocampal function can be observed independently of structural abnormalities of the hippocampus in depression