Publications by authors named "T Aach"

38 Publications

Measuring the regulation of keratin filament network dynamics.

Proc Natl Acad Sci U S A 2013 Jun 11;110(26):10664-9. Epub 2013 Jun 11.

Institute of Molecular and Cellular Anatomy, RWTH Aachen University, 52074 Aachen, Germany.

The organization of the keratin intermediate filament cytoskeleton is closely linked to epithelial function. To study keratin network plasticity and its regulation at different levels, tools are needed to localize and measure local network dynamics. In this paper, we present image analysis methods designed to determine the speed and direction of keratin filament motion and to identify locations of keratin filament polymerization and depolymerization at subcellular resolution. Using these methods, we have analyzed time-lapse fluorescence recordings of fluorescent keratin 13 in human vulva carcinoma-derived A431 cells. The fluorescent keratins integrated into the endogenous keratin cytoskeleton, and thereby served as reliable markers of keratin dynamics. We found that increased times after seeding correlated with down-regulation of inward-directed keratin filament movement. Bulk flow analyses further revealed that keratin filament polymerization in the cell periphery and keratin depolymerization in the more central cytoplasm were both reduced. Treating these cells and other human keratinocyte-derived cells with EGF reversed all these processes within a few minutes, coinciding with increased keratin phosphorylation. These results highlight the value of the newly developed tools for identifying modulators of keratin filament network dynamics and characterizing their mode of action, which, in turn, contributes to understanding the close link between keratin filament network plasticity and epithelial physiology.
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http://dx.doi.org/10.1073/pnas.1306020110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696749PMC
June 2013

Signal and noise modeling in confocal laser scanning fluorescence microscopy.

Med Image Comput Comput Assist Interv 2012 ;15(Pt 1):381-8

Institute of Imaging and Computer Vision, RWTH Aachen University, Germany.

Fluorescence confocal laser scanning microscopy (CLSM) has revolutionized imaging of subcellular structures in biomedical research by enabling the acquisition of 3D time-series of fluorescently-tagged proteins in living cells, hence forming the basis for an automated quantification of their morphological and dynamic characteristics. Due to the inherently weak fluorescence, CLSM images exhibit a low SNR. We present a novel model for the transfer of signal and noise in CLSM that is both theoretically sound as well as corroborated by a rigorous analysis of the pixel intensity statistics via measurement of the 3D noise power spectra, signal-dependence and distribution. Our model provides a better fit to the data than previously proposed models. Further, it forms the basis for (i) the simulation of the CLSM imaging process indispensable for the quantitative evaluation of CLSM image analysis algorithms, (ii) the application of Poisson denoising algorithms and (iii) the reconstruction of the fluorescence signal.
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http://dx.doi.org/10.1007/978-3-642-33415-3_47DOI Listing
January 2013

Comprehensive validation of computational fluid dynamics simulations of in-vivo blood flow in patient-specific cerebral aneurysms.

Med Phys 2012 Feb;39(2):742-54

Philips Research Laboratories, Weisshausstrasse 2, 52066 Aachen, Germany.

Purpose: Recently, image-based computational fluid dynamic (CFD) simulations have been proposed to investigate the local hemodynamics inside human cerebral aneurysms. It was suggested that the knowledge of the computed three-dimensional flow fields can be used to assist clinical risk assessment and treatment decision making. Therefore, it was desired to know the reliability of CFD for cerebral blood flow simulation, and be able to provide clinical feedback. However, the validations were not yet comprehensive as they lack either patient-specific boundary conditions (BCs) required for CFD simulations or quantitative comparison methods.

Methods: In this study, based on a recently proposed in-vitro quantitative CFD evaluation approach via virtual angiography, the CFD evaluation was extended from phantom to patient studies. In contrast to previous work, patient-specific blood flow rates obtained by transcranial color coded Doppler ultrasound measurements were used to impose CFD BCs. Virtual angiograms (VAs) were constructed which resemble clinically acquired angiograms (AAs). Quantitative measures were defined to thoroughly evaluate the correspondence of the detailed flow features between the AAs and the VAs, and thus, the reliability of CFD simulations.

Results: The proposed simulation pipeline provided a comprehensive validation method of CFD simulation for reproducing cerebral blood flow, with a focus on the aneurysm region. Six patient cases were tested and close similarities were found in terms of spatial and temporal variations of contrast agent (CA) distribution between AAs and VAs. For patient #1 to #5, discrepancies of less than 11% were found for the relative root mean square errors in time intensity curve comparisons from characteristic vasculature positions. For patient #6, where the CA concentration curve at vessel inlet cannot be directly extracted from the AAs and given as a BC, deviations about 20% were found.

Conclusions: As a conclusion, the reliability of the CFD simulations was well confirmed. Besides, it was shown that the accuracy of CFD simulations was closely related to the input BCs.
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http://dx.doi.org/10.1118/1.3675402DOI Listing
February 2012

3D segmentation of keratin intermediate filaments in confocal laser scanning microscopy.

Annu Int Conf IEEE Eng Med Biol Soc 2011 ;2011:7751-4

Institute of Imaging & Computer Vision, RWTH Aachen University, 52056 Aachen, Germany.

In this paper, we propose and compare different methods for the 3D segmentation of keratin intermediate filaments (KFs) in images acquired using confocal laser scanning microscopy (CLSM). KFs are elastic cables forming a complex scaffolding within epithelial cells. They are involved in many basic cell functions. To understand the mechanisms of filament formation and network organisation under physiological and pathological conditions, quantitative measurements of dynamic network alterations are essential. Segmenting KFs is a key component for analyzing their dynamic and biomechanical properties. KFs were labeled with fluorescent keratins to allow high resolution imaging of network dynamics in native cells. Our segmentation methods follow the principle of ridge enhancement filtering and subsequent centerline extraction. The evaluation of the methods is two-fold: (i) We develop synthetic data that exhibit the characteristics of real CLSM data to evaluate the precision of the different methods in terms of centerline localisation and (ii) we perform a connected component analysis on the segmentation results of real KF data to assess whether the connectivity of highly complex networks is being preserved by the segmentation. Our evaluation shows that in the presence of strong noise and despite the highly anisotropic spatial resolution of CLSM images the proposed method is able to accurately localize the centerlines of the KFs and to preserve the KF networks' connectivity. Taken together this is a strong indicator that also the network topology is being preserved.
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http://dx.doi.org/10.1109/IEMBS.2011.6091910DOI Listing
May 2012

Gap detection in endoscopic video sequences using graphs.

Annu Int Conf IEEE Eng Med Biol Soc 2011 ;2011:6635-8

of Imaging & Computer Vision, Faculty of Electrical Engineering and Information Technology, RWTH Aachen University, Germany.

In minimal invasive surgery (MIS) a complete and seamless inspection of organs, e.g. the urinary bladder, using video endoscopes is often required for diagnostics. Since the endoscope is usually guided by free-hand, it is difficult to ensure a sequence of seamless frame transitions. Also 2-D panoramic images showing an extended field of view (FOV) do not provide always reliable results, since their interpretations are limited by potentially strong geometric distortions. To overcome these limitations and provide a direct verification method, we develop a gap detection algorithm using graphs. Exploiting the motion information of the applied zig-zag scan, we construct a graph representation of the video sequence. Without any explicit global image visualization our graph search algorithm identifies reliably frame discontinuities, which would lead to holes and slit artifacts in a panoramic view. The algorithm shows high detection rates and provides a fast method to verify frame discontinuities in the whole video sequence. Missed regions are highlighted by local image compositions which can be displayed during the intervention for assistance and inspection control.
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http://dx.doi.org/10.1109/IEMBS.2011.6091636DOI Listing
August 2012
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