Level-Set Based Artery-Vein Separation in Blood Pool Agent CE-MR Angiograms

Blood pool agents (BPAs) for contrast-enhanced (CE) magnetic-resonance angiography (MRA) allow prolonged imaging times for higher contrast and resolution. Imaging is performed during the steady state when the contrast agent is distributed through the complete vascular system. However, simultaneous venous and arterial enhancement in this steady state hampers interpretation. In order to improve visualization of the arteries and veins from steady-state BPA data, a semiautomated method for artery-vein separation is presented. In this method, the central arterial axis and central venous axis are used as initializations for two surfaces that simultaneously evolve in order to capture the arterial and venous parts of the vasculature using the level-set framework. Since arteries and veins can be in close proximity of each other, leakage from the evolving arterial (venous) surface into the venous (arterial) part of the vasculature is inevitable. In these situations, voxels are labeled arterial or venous based on the arrival time of the respective surface. The evolution is steered by external forces related to feature images derived from the image data and by internal forces related to the geometry of the level sets. In this paper, the robustness and accuracy of three external forces (based on image intensity, image gradient, and vessel-enhancement filtering) and combinations of them are investigated and tested on seven patient datasets. To this end, results with the level-set-based segmentation are compared to the reference-standard manually obtained segmentations. Best results are achieved by applying a combination of intensity- and gradient-based forces and a smoothness constraint based on the curvature of the surface. By applying this combination to the seven datasets, it is shown that, with minimal user interaction, artery-vein separation for improved arterial and venous visualization in BPA CE-MRA can be achieved

The biodistribution of triamcinolone acetonide injections in severe keloids:an exploratory three-dimensional fluorescent cryomicrotome study

Intralesional corticosteroid injections are a first-line treatment for keloids; yet clinical treatment results are highly variable and often suboptimal. Variation in triamcinolone acetonide (TAC) biodistribution may be an important reason for the variable effects of TAC treatment in keloids. In this exploratory study we investigated the biodistribution of TAC in keloids and normal skin using different drug delivery techniques. Fluorescent-labeled TAC suspension was administered into keloids and normal skin with a hypodermic needle and an electronic pneumatic jet injector. TAC biodistribution was represented by the fluorescent TAC volume and 3D biodistribution shape of TAC, using a 3D-Fluorescence-Imaging Cryomicrotome System. Twenty-one keloid and nine normal skin samples were analyzed. With needle injections, the mean fluorescent TAC volumes were 990 µl ± 479 in keloids and 872 µl ± 227 in normal skin. With the jet injector, the mean fluorescent TAC volumes were 401 µl ± 252 in keloids and 249 µl ± 67 in normal skin. 3D biodistribution shapes of TAC were highly variable in keloids and normal skin. In conclusion, TAC biodistribution in keloids is highly variable for both needle and jet injection. This may partly explain the variable treatment effects of intralesional TAC in keloids. Future research is needed to confirm this preliminary finding and to optimize drug delivery in keloids.</p

Heritability of the shape of subcortical brain structures in the general population

The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures

Genetic variation underlying cognition and its relation with neurological outcomes and brain imaging

Cognition in adults shows variation due to developmental and degenerative components. A recent genome‐ wide association study identified genetic variants for general cognitive function in 148 independent loci. Here, we aimed to elucidate possible developmental and neurodegenerative pathways underlying these genetic variants by relating them to functional, clinical and neuroimaging outcomes. This study was conducted within the population‐based Rotterdam Study (N=11,496, mean age 65.3±9.9 years, 58.0% female). We used lead variants for general cognitive function to construct a polygenic score (PGS), and additionally excluded developmental variants at multiple significance thresholds. A higher PGS was related to more years of education (β=0.29, p=4.3x10‐7 ) and a larger intracranial volume (β=0.05, p=7.5x10‐4 ). To a smaller extent, the PGS was associated with less cognitive decline (βΔG‐factor=0.03, p=1.3x10‐3 ), which became non‐significant after adjusting for education (p=1.6x10‐2 ). No associations were found with daily functioning, dementia, parkinsonism, stroke or microstructural white matter integrity. Excluding developmental variants attenuated nearly all associations. In conclusion, this study suggests that the genetic variants identified for general cognitive function are acting mainly through the developmental pathway of cognition. Therefore, cognition, assessed cross‐sectionally, seems to have limited value as a biomarker for neurodegeneration

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Level-Set Based Carotid Artery Segmentation for Stenosis Grading

A semi-automated method is presented for the determination of the degree of stenosis of the internal carotid artery (ICA) in 3D contrast-enhanced (CE) MR angiograms. Hereto, we determined the central vessel axis (CA), which subsequently is used as an initialization for a level-set based segmentation of the stenosed carotid artery. The degree of stenosis is determined by calculating the average diameters of cross-sectional planes along the CA. For twelve ICAs the degree of stenosis was determined and correlated with the scores of two experts (NASCET criterion). The Spearman’s correlation coefficient for the proposed method was 0.96 (p<0.001), versus 0.89 and 0.88 (p<0.001) for the manual scores, and a smaller bias and tighter confidence bounds for the automated method were found

Blood Pool Agent Contrast-Enhanced MRA: Level-Set Based Artery-Vein Separation

Blood pool agents (BPAs) for contrast-enhanced magnetic resonance angiography (CE-MRA) allow prolonged imaging times for higher contrast and resolution by imaging during the steady state when the contrast agent is distributed through the complete vascular system. However, simultaneous arterial and venous enhancement hampers interpretation. It is shown that venous and arterial segmentation in this equilibrium phase can be achieved if the central arterial axis (CAA) and central venous axis (CVA) are known. Since the CAA cannot straightforwardly be obtained from the steady-state data, images acquired during the first pass of the contrast agent can be utilized to determine the CAA with minimal user initialization. Utilizing the CAA to provide a rough arterial segmentation, the CVA can subsequently be determined from the steady-state dataset. The final segmentations of the arteries and veins are achieved by simultaneously evolving two level-sets in the steady-state dataset starting from the CAA and CVA

Fibrinogen determination according to Clauss: commutability assessment of International and commercial standards and quality control samples

Thrombosis and Hemostasi

In a clinimetric analysis, 3D stereophotogrammetry was found to be reliable and valid for measuring scar volume in clinical research

Objectives Volume is an important feature in the evaluation of hypertrophic scars and keloids. Three-dimensional (3D) stereophotogrammetry is a noninvasive technique for the measurement of scar volume. This study evaluated the reliability and validity of 3D stereophotogrammetry for measuring scar volume. Study Design and Setting To evaluate reliability, 51 scars were photographed by two observers. Interobserver reliability was assessed by the intraclass correlation coefficient (ICC), and the measurement error was expressed as limits of agreement (LoA). To assess validity, 60 simulated (clay) scars were measured by 3D stereophotogrammetry and subsequently weighed (gold standard). The correlation of volumes obtained by both measures was calculated by a concordance correlation coefficient (CCC), and the measurement error was expressed as a 95% prediction interval. Results The ICC was 0.99, corresponding to a high correlation of measurements between two observers, although the LoA were relatively wide. The correlation between 3D stereophotogrammetry and the gold standard was also high, with a CCC of 0.97. Again, the plot of the differences and LoA showed moderate agreement for the validity. Conclusion Three-dimensional stereophotogrammetry is suitable for the use in clinical research but not for the follow-up of the individual patient