Pancreas MRI segmentation into head, body, and tail enables regional quantitative analysis of heterogeneous disease

Background: Quantitative imaging studies of the pancreas have often targeted the three main anatomical segments, head, body, and tail, using manual region of interest strategies to assess geographic heterogeneity. Existing automated analyses have implemented whole-organ segmentation, providing overall quantification but failing to address spatial heterogeneity. Purpose: To develop and validate an automated method for pancreas segmentation into head, body, and tail subregions in abdominal MRI. Study Type: Retrospective. Subjects: One hundred and fifty nominally healthy subjects from UK Biobank (100 subjects for method development and 50 subjects for validation). A separate 390 UK Biobank triples of subjects including type 2 diabetes mellitus (T2DM) subjects and matched nondiabetics. Field strength/Sequence: A 1.5 T, three-dimensional two-point Dixon sequence (for segmentation and volume assessment) and a two-dimensional axial multiecho gradient-recalled echo sequence. Assessment: Pancreas segments were annotated by four raters on the validation cohort. Intrarater agreement and interrater agreement were reported using Dice overlap (Dice similarity coefficient [DSC]). A segmentation method based on template registration was developed and evaluated against annotations. Results on regional pancreatic fat assessment are also presented, by intersecting the three-dimensional parts segmentation with one available proton density fat fraction (PDFF) image. Statistical Test: Wilcoxon signed rank test and Mann–Whitney U-test for comparisons. DSC and volume differences for evaluation. A P value  Results: Good intrarater (DSC mean, head: 0.982, body: 0.940, tail: 0.961) agreement and interrater (DSC mean, head: 0.968, body: 0.905, tail: 0.943) agreement were observed. No differences (DSC, head: P = 0.4358, body: P = 0.0992, tail: P = 0.1080) were observed between the manual annotations and our method's segmentations (DSC mean, head: 0.965, body: 0.893, tail: 0.934). Pancreatic body PDFF was different between T2DM and nondiabetics matched by body mass index. Data Conclusion: The developed segmentation's performance was no different from manual annotations. Application on type 2 diabetes subjects showed potential for assessing pancreatic disease heterogeneity. Level of Evidence: 4 Technical Efficacy Stage: 3

Abstract conceptual feature ratings: the role of emotion, magnitude, and other cognitive domains in the organization of abstract conceptual knowledge.

This study harnessed control ratings of the contribution of different types of information (sensation, action, emotion, thought, social interaction, morality, time, space, quantity, and polarity) to 400 individual abstract and concrete verbal concepts. These abstract conceptual feature (ACF) ratings were used to generate a high dimensional semantic space, from which Euclidean distance measurements between individual concepts were extracted as a metric of the semantic relatedness of those words. The validity of these distances as a marker of semantic relatedness was then tested by evaluating whether they could predict the comprehension performance of a patient with global aphasia on two verbal comprehension tasks. It was hypothesized that if the high-dimensional space generated from ACF control ratings approximates the organization of abstract conceptual space, then words separated by small distances should be more semantically related than words separated by greater distances, and should therefore be more difficult to distinguish for the comprehension-impaired patient, SKO. SKO was significantly worse at identifying targets presented within word pairs with low ACF distances. Response accuracy was not predicted by Latent Semantic Analysis (LSA) cosines, any of the individual feature ratings, or any of the background variables. It is argued that this novel rating procedure provides a window on the semantic attributes of individual abstract concepts, and that multiple cognitive systems may influence the acquisition and organization of abstract conceptual knowledge. More broadly, it is suggested that cognitive models of abstract conceptual knowledge must account for the representation not only of the relationships between abstract concepts but also of the attributes which constitute those individual concepts

Targeted regeneration of bone in the osteoporotic human femur.

We have recently developed image processing techniques for measuring the cortical thicknesses of skeletal structures in vivo, with resolution surpassing that of the underlying computed tomography system. The resulting thickness maps can be analysed across cohorts by statistical parametric mapping. Applying these methods to the proximal femurs of osteoporotic women, we discover targeted and apparently synergistic effects of pharmaceutical osteoporosis therapy and habitual mechanical load in enhancing bone thickness

Impairments of auditory scene analysis in Alzheimer's disease

Parsing of sound sources in the auditory environment or ‘auditory scene analysis’ is a computationally demanding cognitive operation that is likely to be vulnerable to the neurodegenerative process in Alzheimer’s disease. However, little information is available concerning auditory scene analysis in Alzheimer's disease. Here we undertook a detailed neuropsychological and neuroanatomical characterization of auditory scene analysis in a cohort of 21 patients with clinically typical Alzheimer's disease versus age-matched healthy control subjects. We designed a novel auditory dual stream paradigm based on synthetic sound sequences to assess two key generic operations in auditory scene analysis (object segregation and grouping) in relation to simpler auditory perceptual, task and general neuropsychological factors. In order to assess neuroanatomical associations of performance on auditory scene analysis tasks, structural brain magnetic resonance imaging data from the patient cohort were analysed using voxel-based morphometry. Compared with healthy controls, patients with Alzheimer's disease had impairments of auditory scene analysis, and segregation and grouping operations were comparably affected. Auditory scene analysis impairments in Alzheimer's disease were not wholly attributable to simple auditory perceptual or task factors; however, the between-group difference relative to healthy controls was attenuated after accounting for non-verbal (visuospatial) working memory capacity. These findings demonstrate that clinically typical Alzheimer's disease is associated with a generic deficit of auditory scene analysis. Neuroanatomical associations of auditory scene analysis performance were identified in posterior cortical areas including the posterior superior temporal lobes and posterior cingulate. This work suggests a basis for understanding a class of clinical symptoms in Alzheimer's disease and for delineating cognitive mechanisms that mediate auditory scene analysis both in health and in neurodegenerative disease

Stellar Diameters and Temperatures. I. Main-Sequence A, F, and G Stars

We have executed a survey of nearby, main-sequence A-, F-, and G-type stars with the CHARA Array, successfully measuring the angular diameters of forty-four stars with an average precision of ~1.5%. We present new measures of the bolometric flux, which in turn leads to an empirical determination of the effective temperature for the stars observed. In addition, these CHARA-determined temperatures, radii, and luminosities are fit to Yonsei-Yale model isochrones to constrain the masses and ages of the stars. These results are compared to indirect estimates of these quantities obtained by collecting photometry of the stars and applying them to model atmospheres and evolutionary isochrones. We find that for most cases, the models overestimate the effective temperature by ~1.5%-4% when compared to our directly measured values. The overestimated temperatures and underestimated radii in these works appear to cause an additional offset in the star's surface gravity measurements, which consequently yield higher masses and younger ages, in particular for stars with masses greater than ~1.3 M_☉. Additionally, we compare our measurements to a large sample of eclipsing binary stars, and excellent agreement is seen within both data sets. Finally, we present temperature relations with respect to (B – V) and (V – K) colors as well as spectral type, showing that calibration of effective temperatures with errors ~1% is now possible from interferometric angular diameters of stars

Patterns of progressive atrophy vary with age in Alzheimer's disease patients.

Age is not only the greatest risk factor for Alzheimer's disease (AD) but also a key modifier of disease presentation and progression. Here, we investigate how longitudinal atrophy patterns vary with age in mild cognitive impairment (MCI) and AD. Data comprised serial longitudinal 1.5-T magnetic resonance imaging scans from 153 AD, 339 MCI, and 191 control subjects. Voxel-wise maps of longitudinal volume change were obtained and aligned across subjects. Local volume change was then modeled in terms of diagnostic group and an interaction between group and age, adjusted for total intracranial volume, white-matter hyperintensity volume, and apolipoprotein E genotype. Results were significant at p < 0.05 with family-wise error correction for multiple comparisons. An age-by-group interaction revealed that younger AD patients had significantly faster atrophy rates in the bilateral precuneus, parietal, and superior temporal lobes. These results suggest younger AD patients have predominantly posterior progressive atrophy, unexplained by white-matter hyperintensity, apolipoprotein E, or total intracranial volume. Clinical trials may benefit from adapting outcome measures for patient groups with lower average ages, to capture progressive atrophy in posterior cortices

Prominent effects and neural correlates of visual crowding in a neurodegenerative disease population.

Crowding is a breakdown in the ability to identify objects in clutter, and is a major constraint on object recognition. Crowding particularly impairs object perception in peripheral, amblyopic and possibly developing vision. Here we argue that crowding is also a critical factor limiting object perception in central vision of individuals with neurodegeneration of the occipital cortices. In the current study, individuals with posterior cortical atrophy (n=26), typical Alzheimer's disease (n=17) and healthy control subjects (n=14) completed centrally-presented tests of letter identification under six different flanking conditions (unflanked, and with letter, shape, number, same polarity and reverse polarity flankers) with two different target-flanker spacings (condensed, spaced). Patients with posterior cortical atrophy were significantly less accurate and slower to identify targets in the condensed than spaced condition even when the target letters were surrounded by flankers of a different category. Importantly, this spacing effect was observed for same, but not reverse, polarity flankers. The difference in accuracy between spaced and condensed stimuli was significantly associated with lower grey matter volume in the right collateral sulcus, in a region lying between the fusiform and lingual gyri. Detailed error analysis also revealed that similarity between the error response and the averaged target and flanker stimuli (but not individual target or flanker stimuli) was a significant predictor of error rate, more consistent with averaging than substitution accounts of crowding. Our findings suggest that crowding in posterior cortical atrophy can be regarded as a pre-attentive process that uses averaging to regularize the pathologically noisy representation of letter feature position in central vision. These results also help to clarify the cortical localization of feature integration components of crowding. More broadly, we suggest that posterior cortical atrophy provides a neurodegenerative disease model for exploring the basis of crowding. These data have significant implications for patients with, or who will go on to develop, dementia-related visual impairment, in whom acquired excessive crowding likely contributes to deficits in word, object, face and scene perception

MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment