Publications by authors named "Til Aach"

29 Publications

  • Page 1 of 1

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

Inertial navigation system for bladder endoscopy.

Annu Int Conf IEEE Eng Med Biol Soc 2011 ;2011:5376-9

Faculty of Electrical Engineering and Information Technology, Institute of Imaging, & Computer Vision, RWTH Aachen University, Aachen 52062, Germany.

The usage of video endoscopes in cystoscopic interventions of the urinary bladder impedes an intuitive navigation. Although image-based solutions such as panorama images can provide extended views of the surgical field, a real-time 3-D navigation is not supported. Furthermore, the integration of common tracking systems in ambulant clinics is often hindered due to low usability and high costs. Thus, we discuss in this paper a first low-cost inertial navigation system. Our evaluation results show that in spite of lower sensor accuracies, mean errors between < 1° and 4° are achieved for solid angles. Using endoscopes with different view angles we apply an extended endoscope model for an adaptive displacement correction. Furthermore, we implement a first guided navigation tool for tumor re-identification in real-time.
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http://dx.doi.org/10.1109/IEMBS.2011.6091330DOI Listing
June 2012

Computer-based classification of small colorectal polyps by using narrow-band imaging with optical magnification.

Gastrointest Endosc 2011 Dec 13;74(6):1354-9. Epub 2011 Oct 13.

Medical Department III (Gastroenterology, Hepatology, and Metabolic Diseases), University Hospital RWTH Aachen, Aachen, Germany.

Background: Recent studies have shown that narrow-band imaging (NBI) is a powerful diagnostic tool for the differentiation between neoplastic and non-neoplastic colorectal polyps.

Objective: To develop a computer-based method for classification of colorectal polyps.

Design: A prospective study.

Setting: University hospital.

Patients: A total of 214 patients with colorectal polyps who underwent a zoom NBI colonoscopy.

Interventions: A total of 434 detected polyps 10 mm or smaller were imaged and subsequently removed for histological analysis.

Main Outcome Measurements: Diagnostic performance in polyp classification by 2 experts, 2 nonexperts, and a computer-based algorithm.

Results: The expert group and the computer-based algorithm achieved a comparable diagnostic performance (expert group: 93.4% sensitivity, 91.8% specificity, and 92.7% accuracy; computer-based algorithm: 95.0% sensitivity, 90.3% specificity, and 93.1% accuracy) and were both significantly superior to the nonexpert group (86.0% sensitivity, 87.8% specificity, and 86.8% accuracy) in terms of sensitivity, negative predictive value, and accuracy. Subgroup analysis of 255 polyps 5 mm or smaller revealed comparable results without significant differences in the overall analysis of all polyps.

Limitations: No fully automatic classification system.

Conclusions: The study demonstrates that computer-based classification of colon polyps can be achieved with high diagnostic performance.
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http://dx.doi.org/10.1016/j.gie.2011.08.001DOI Listing
December 2011

Activity quantification combining conjugate-view planar scintigraphies and SPECT/CT data for patient-specific 3-D dosimetry in radionuclide therapy.

Eur J Nucl Med Mol Imaging 2011 Dec 8;38(12):2173-85. Epub 2011 Sep 8.

Department of Experimental Molecular Imaging, RWTH Aachen University Hospital, Pauwelsstraße 30, 52074 Aachen, Germany.

Purpose: Three-dimensional dosimetry based on quantitative SPECT/CT has potential advantages over planar approaches, but may be impractical due to acquisition durations. We combine one SPECT/CT with improved quantification of multiple planar scintigraphies to shorten acquisitions.

Methods: A hybrid 2-D/3-D quantification technique is proposed, using SPECT/CT information for robust planar image quantification and creating virtual SPECTs out of conjugate-view planar scintigraphies; these are included in a 3-D absorbed dose calculation. A projection model simulates photon attenuation and scatter as well as camera and collimator effects. Planar and SPECT calibration techniques are described, offering multiple pathways of deriving calibration factors for hybrid quantification. Model, phantom and patient data are used to validate the approach on a per-organ basis, and the similarity of real and virtual SPECTs, and of planar images and virtual SPECT projections, is assessed using linear regression analysis.

Results: Organ overlap, background activity and organ geometry are accounted for in the algorithm. Hybrid time-activity curves yield the same information as those derived from a conventional SPECT evaluation. Where correct values are known, hybrid quantification errors are less than 16% for all but two compartments (SPECT/CT 23%). Under partial volume effects, hybrid quantification can provide more robust results than SPECT/CT. The mean correlation coefficient of 3-D data is 0.962 (2-D 0.934). As a consequence of good activity quantification performance, good agreement of absorbed dose estimates and dose-volume histograms with reference results is achieved.

Conclusion: The proposed activity quantification method for 2-D scintigraphies can speed up SPECT/CT-based 3-D dosimetry without losing accuracy.
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http://dx.doi.org/10.1007/s00259-011-1889-7DOI Listing
December 2011

Design and implementation of multisteerable matched filters.

IEEE Trans Pattern Anal Mach Intell 2012 Feb;34(2):279-91

CanControls, Vaalser Strasse 259, Aachen D-52074, Germany.

Image analysis problems such as feature tracking, edge detection, image enhancement, or texture analysis require thedetection of multi-oriented patterns which can appear at arbitrary orientations. Direct rotated matched filtering for feature detection is computationally expensive, but can be sped up with steerable filters. So far, steerable filter approaches were limited to only one direction. Many important low-level image features are, however, characterized by more than a single orientation. We therefore present here a framework for efficiently detecting specific multi-oriented patterns with arbitrary orientations in grayscale images. The core idea is to construct multisteerable filters by appropriate combinations of single-steerable filters. We exploit that steerable filters are closed under addition and multiplication. This allows to derive a design guide for multisteerable filters by means of multivariate polynomials. Furthermore, we describe an efficient implementation scheme and discuss the use of weighting functions to reduce angular oscillations. Applications in camera calibration, junction analysis of images from plant roots, and the discrimination of L, T, and X-junctions demonstrate the potential of this approach.
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http://dx.doi.org/10.1109/TPAMI.2011.143DOI Listing
February 2012

Venous tree separation in the liver: graph partitioning using a non-ising model.

Inf Process Med Imaging 2011 ;22:197-207

Siemens Corporate Research, 755 College Rd East, Princeton, NJ 08540, USA.

Entangled tree-like vascular systems are commonly found in the body (e.g., in the peripheries and lungs). Separation of these systems in medical images may be formulated as a graph partitioning problem given an imperfect segmentation and specification of the tree roots. In this work, we show that the ubiquitous Ising-model approaches (e.g., Graph Cuts, Random Walker) are not appropriate for tackling this problem and propose a novel method based on recursive minimal paths for doing so. To motivate our method, we focus on the intertwined portal and hepatic venous systems in the liver. Separation of these systems is critical for liver intervention planning, in particular when resection is involved. We apply our method to 34 clinical datasets, each containing well over a hundred vessel branches, demonstrating its effectiveness.
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http://dx.doi.org/10.1007/978-3-642-22092-0_17DOI Listing
August 2011

Simultaneous reconstruction of activity and attenuation for PET/MR.

IEEE Trans Med Imaging 2011 Mar 29;30(3):804-13. Epub 2010 Nov 29.

Philips Research Europe, Molecular Imaging Systems Department, 52066 Aachen, Germany.

Medical investigations targeting a quantitative analysis of the position emission tomography (PET) images require the incorporation of additional knowledge about the photon attenuation distribution in the patient. Today, energy range adapted attenuation maps derived from computer tomography (CT) scans are used to effectively compensate for image quality degrading effects, such as attenuation and scatter. Replacing CT by magnetic resonance (MR) is considered as the next evolutionary step in the field of hybrid imaging systems. However, unlike CT, MR does not measure the photon attenuation and thus does not provide an easy access to this valuable information. Hence, many research groups currently investigate different technologies for MR-based attenuation correction (MR-AC). Typically, these approaches are based on techniques such as special acquisition sequences (alone or in combination with subsequent image processing), anatomical atlas registration, or pattern recognition techniques using a data base of MR and corresponding CT images. We propose a generic iterative reconstruction approach to simultaneously estimate the local tracer concentration and the attenuation distribution using the segmented MR image as anatomical reference. Instead of applying predefined attenuation values to specific anatomical regions or tissue types, the gamma attenuation at 511 keV is determined from the PET emission data. In particular, our approach uses a maximum-likelihood estimation for the activity and a gradient-ascent based algorithm for the attenuation distribution. The adverse effects of scattered and accidental gamma coincidences on the quantitative accuracy of PET, as well as artifacts caused by the inherent crosstalk between activity and attenuation estimation are efficiently reduced using enhanced decay event localization provided by time-of-flight PET, accurate correction for accidental coincidences, and a reduced number of unknown attenuation coefficients. First results achieved with measured whole body PET data and reference segmentation from CT showed an absolute mean difference of 0.005 cm⁻¹ (< 20%) in the lungs, 0.0009 cm⁻¹ (< 2%) in case of fat, and 0.0015 cm⁻¹ (< 2%) for muscles and blood. The proposed method indicates a robust and reliable alternative to other MR-AC approaches targeting patient specific quantitative analysis in time-of-flight PET/MR.
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http://dx.doi.org/10.1109/TMI.2010.2095464DOI Listing
March 2011

Phantom-based experimental validation of computational fluid dynamics simulations on cerebral aneurysms.

Med Phys 2010 Sep;37(9):5054-65

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

Purpose: Recently, image-based computational fluid dynamics (CFD) simulation has been applied to investigate the hemodynamics inside human cerebral aneurysms. The knowledge of the computed three-dimensional flow fields is used for clinical risk assessment and treatment decision making. However, the reliability of the application specific CFD results has not been thoroughly validated yet.

Methods: In this work, by exploiting a phantom aneurysm model, the authors therefore aim to prove the reliability of the CFD results obtained from simulations with sufficiently accurate input boundary conditions. To confirm the correlation between the CFD results and the reality, virtual angiograms are generated by the simulation pipeline and are quantitatively compared to the experimentally acquired angiograms. In addition, a parametric study has been carried out to systematically investigate the influence of the input parameters associated with the current measuring techniques on the flow patterns.

Results: Qualitative and quantitative evaluations demonstrate good agreement between the simulated and the real flow dynamics. Discrepancies of less than 15% are found for the relative root mean square errors of time intensity curve comparisons from each selected characteristic position. The investigated input parameters show different influences on the simulation results, indicating the desired accuracy in the measurements.

Conclusions: This study provides a comprehensive validation method of CFD simulation for reproducing the real flow field in the cerebral aneurysm phantom under well controlled conditions. The reliability of the CFD is well confirmed. Through the parametric study, it is possible to assess the degree of validity of the associated CFD model based on the parameter values and their estimated accuracy range.
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http://dx.doi.org/10.1118/1.3483066DOI Listing
September 2010

Geometric calibration of lens and filter distortions for multispectral filter-wheel cameras.

IEEE Trans Image Process 2011 Feb 29;20(2):496-505. Epub 2010 Jul 29.

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

High-fidelity color image acquisition with a multispectral camera utilizes optical filters to separate the visible electromagnetic spectrum into several passbands. This is often realized with a computer-controlled filter wheel, where each position is equipped with an optical bandpass filter. For each filter wheel position, a grayscale image is acquired and the passbands are finally combined to a multispectral image. However, the different optical properties and non-coplanar alignment of the filters cause image aberrations since the optical path is slightly different for each filter wheel position. As in a normal camera system, the lens causes additional wavelength-dependent image distortions called chromatic aberrations. When transforming the multispectral image with these aberrations into an RGB image, color fringes appear, and the image exhibits a pincushion or barrel distortion. In this paper, we address both the distortions caused by the lens and by the filters. Based on a physical model of the bandpass filters, we show that the aberrations caused by the filters can be modeled by displaced image planes. The lens distortions are modeled by an extended pinhole camera model, which results in a remaining mean calibration error of only 0.07 pixels. Using an absolute calibration target, we then geometrically calibrate each passband and compensate for both lens and filter distortions simultaneously. We show that both types of aberrations can be compensated and present detailed results on the remaining calibration errors.
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http://dx.doi.org/10.1109/TIP.2010.2062193DOI Listing
February 2011

Range flow in varying illumination: algorithms and comparisons.

IEEE Trans Pattern Anal Mach Intell 2010 Sep;32(9):1646-58

Fraunhofer Institute of Optronics, System Technologies and Image Exploitation IOSB, Karlsruhe, Germany.

We extend estimation of range flow to handle brightness changes in image data caused by inhomogeneous illumination. Standard range flow computes 3D velocity fields using both range and intensity image sequences. Toward this end, range flow estimation combines a depth change model with a brightness constancy model. However, local brightness is generally not preserved when object surfaces rotate relative to the camera or the light sources, or when surfaces move in inhomogeneous illumination. We describe and investigate different approaches to handle such brightness changes. A straightforward approach is to prefilter the intensity data such that brightness changes are suppressed, for instance, by a highpass or a homomorphic filter. Such prefiltering may, though, reduce the signal-to-noise ratio. An alternative novel approach is to replace the brightness constancy model by 1) a gradient constancy model, or 2) by a combination of gradient and brightness constancy constraints used earlier successfully for optical flow, or 3) by a physics-based brightness change model. In performance tests, the standard version and the novel versions of range flow estimation are investigated using prefiltered or nonprefiltered synthetic data with available ground truth. Furthermore, the influences of additive Gaussian noise and simulated shot noise are investigated. Finally, we compare all range flow estimators on real data.
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http://dx.doi.org/10.1109/TPAMI.2009.162DOI Listing
September 2010

The keratin-filament cycle of assembly and disassembly.

J Cell Sci 2010 Jul;123(Pt 13):2266-72

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

Continuous and regulated remodelling of the cytoskeleton is crucial for many basic cell functions. In contrast to actin filaments and microtubules, it is not understood how this is accomplished for the third major cytoskeletal filament system, which consists of intermediate-filament polypeptides. Using time-lapse fluorescence microscopy of living interphase cells, in combination with photobleaching, photoactivation and quantitative fluorescence measurements, we observed that epithelial keratin intermediate filaments constantly release non-filamentous subunits, which are reused in the cell periphery for filament assembly. This cycle is independent of protein biosynthesis. The different stages of the cycle occur in defined cellular subdomains: assembly takes place in the cell periphery and newly formed filaments are constantly transported toward the perinuclear region while disassembly occurs, giving rise to diffusible subunits for another round of peripheral assembly. Remaining juxtanuclear filaments stabilize and encage the nucleus. Our data suggest that the keratin-filament cycle of assembly and disassembly is a major mechanism of intermediate-filament network plasticity, allowing rapid adaptation to specific requirements, notably in migrating cells.
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http://dx.doi.org/10.1242/jcs.068080DOI Listing
July 2010

Texture classification by modeling joint distributions of local patterns with gaussian mixtures.

IEEE Trans Image Process 2010 Jun 2;19(6):1548-57. Epub 2010 Feb 2.

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

Texture classification generally requires the analysis of patterns in local pixel neighborhoods. Statistically, the underlying processes are comprehensively described by their joint probability density functions (jPDFs). Even for small neighborhoods, however, stable estimation of jPDFs by joint histograms (jHSTs) is often infeasible, since the number of entries in the jHST exceeds by far the number of pixels in a typical texture region. Moreover, evaluation of distance functions between jHSTs is often computationally prohibitive. Practically, the number of entries in a jHST is therefore reduced by considering only two-pixel patterns, leading to 2D-jHSTs known as cooccurrence matrices, or by quantization of the gray levels in local patterns to only two gray levels, yielding local binary patterns (LBPs). Both approaches result in a loss of information. We introduce here a framework for supervised texture classification which reduces or avoids this information loss. Local texture neighborhoods are first filtered by a filter bank. Without further quantization, the jPDF of the filter responses is then described parametrically by gaussian mixture models (GMMs). We show that the parameters of the GMMs can be reliably estimated from small image regions. Moreover, distances between the thus modelled jPDFs of different texture patterns can be computed efficiently in closed form from their model parameters. We furthermore extend this texture descriptor to achieve full invariance to rotation. We evaluate the framework for different filter banks on the Brodatz texture set. We first show that combining the LBP difference filters with the GMM-based density estimator outperforms the classical LBP approach and its codebook extensions. When replacing these-rather elementary-difference filters by the wavelet frame transform (WFT), the performance of the framework on all 111 Brodatz textures exceeds the one obtained more recently by spin image and RIFT descriptors by Lazebnik et al.
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http://dx.doi.org/10.1109/TIP.2010.2042100DOI Listing
June 2010

Local and global panoramic imaging for fluorescence bladder endoscopy.

Annu Int Conf IEEE Eng Med Biol Soc 2009 ;2009:6990-3

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

Endoscopic treatment of bladder cancer is more and more often based on photodynamic diagnostics (PDD), a specialized endoscopic technique where a narrow-band bluish illumination causes tumors to fluoresce reddish. Contrast between tumors and healthy bladder tissue is thus noticeably increased compared to white light endoscopy. A downside of PDD is the low illumination power, which requires that the distance between endoscope and bladder wall be kept low, thus resulting in a small field of view (FOV). We therefore describe an approach to combine several successive frames into a local PDD panorama, which provides a larger and sufficiently bright FOV for treatment. Furthermore, the endoscopic cancer treatment generally starts with a complete scan of the bladder to detect the tumors. For diagnosis, navigation and reporting, a global overview image of the bladder wall is often desired. While construction of such a global panorama can be based on the same algorithm as the local panorama, direct planar visualization of the sphere-shaped bladder may cause severe distortions. Apart from the global panorama computation itself, we therefore analyze these distortions, and provide an alternative visualization which is based on bladder depictions used in standard reporting forms and anatomy textbooks.
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http://dx.doi.org/10.1109/IEMBS.2009.5333854DOI Listing
April 2010

Temperature responses of roots: impact on growth, root system architecture and implications for phenotyping.

Funct Plant Biol 2009 Nov;36(11):947-959

Institute of Chemistry and Dynamics of the Geosphere ICG-3: Phytosphere, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany.

Root phenotyping is a challenging task, mainly because of the hidden nature of this organ. Only recently, imaging technologies have become available that allow us to elucidate the dynamic establishment of root structure and function in the soil. In root tips, optical analysis of the relative elemental growth rates in root expansion zones of hydroponically-grown plants revealed that it is the maximum intensity of cellular growth processes rather than the length of the root growth zone that control the acclimation to dynamic changes in temperature. Acclimation of entire root systems was studied at high throughput in agar-filled Petri dishes. In the present study, optical analysis of root system architecture showed that low temperature induced smaller branching angles between primary and lateral roots, which caused a reduction in the volume that roots access at lower temperature. Simulation of temperature gradients similar to natural soil conditions led to differential responses in basal and apical parts of the root system, and significantly affected the entire root system. These results were supported by first data on the response of root structure and carbon transport to different root zone temperatures. These data were acquired by combined magnetic resonance imaging (MRI) and positron emission tomography (PET). They indicate acclimation of root structure and geometry to temperature and preferential accumulation of carbon near the root tip at low root zone temperatures. Overall, this study demonstrated the value of combining different phenotyping technologies that analyse processes at different spatial and temporal scales. Only such an integrated approach allows us to connect differences between genotypes obtained in artificial high throughput conditions with specific characteristics relevant for field performance. Thus, novel routes may be opened up for improved plant breeding as well as for mechanistic understanding of root structure and function.
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http://dx.doi.org/10.1071/FP09184DOI Listing
November 2009

Analysis of multiple orientations.

IEEE Trans Image Process 2009 Jul 12;18(7):1424-37. Epub 2009 May 12.

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

Estimation of local orientations in multivariate signals is an important problem in image processing and computer vision. This general problem formulation also covers optical flow estimation, which can be regarded as orientation estimation in space-time-volumes. Modelling a signal using only a single orientation, however, is often too restrictive, since occlusions and transparencies occur frequently, thus necessitating the modelling and analysis of multiple orientations. We, therefore, develop a unifying mathematical model for multiple orientations: Beyond describing an arbitrary number of orientations in scalar- and vector-valued image data such as color image sequences, it allows the unified treatment of additively and occludingly superimposed oriented structures as well as of combinations of these. Based on this model, we describe estimation schemes for an arbitrary number of additively or occludingly superimposed orientations in images. We confirm the performance of our framework on both synthetic and real image data.
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http://dx.doi.org/10.1109/TIP.2009.2019307DOI Listing
July 2009

Toward a multimodal cell analysis of brush biopsies for the early detection of oral cancer.

Cancer 2009 Jun;117(3):228-35

Department of Oral, Maxillofacial, and Plastic Surgery, University of Leipzig, Leipzig, Germany.

Background: This report describes what to the authors' knowledge is the first clinical application of semiautomated multimodal cell analysis (MMCA), a novel technique for the early detection of cancer for cases with a limited number of suspicious cells. In this clinical study, MMCA was applied to oral cancer diagnostics on brush biopsies. The MMCA approach was based on the sequential application of multiple stainings of identical, slide-based cells and repeated relocalizations and measurements of their diagnostic features, resulting in multiparametric features of individual cells. Data integration of the variously stained cells increased diagnostic accuracy. The implementation of MMCA also enabled fully automatic, adaptive image preprocessing, including registration of multimodal images and segmentation of cell nuclei.

Methods: In a preliminary clinical trial, 47 slides from brush biopsies of suspicious oral lesions were analyzed. The final histologic diagnoses included 20 squamous cell carcinomas, 7 hyperkeratotic leukoplakias, and 20 lichen planus mucosae.

Results: The stepwise application of 2 additional approaches (morphology, DNA content, argyrophilic nucleolar organizer region counts) increased the specificity of conventional cytologic diagnosis from 92.6% to 100%. This feasibility study provided a proof of concept, demonstrating efficiency, robustness, and diagnostic accuracy on slide-based cytologic specimens.

Conclusions: The authors concluded that MMCA may become a sensitive and highly specific, objective, and reproducible adjuvant diagnostic tool for the identification of neoplastic changes in oral smears that contain only a few abnormal cells.
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http://dx.doi.org/10.1002/cncy.20028DOI Listing
June 2009

Video-based measuring of quality parameters for tricuspid xenograft heart valve implants.

IEEE Trans Biomed Eng 2009 Dec 20;56(12):2868-78. Epub 2008 Jun 20.

Institute for Signal Processing, Universityof Lübeck, D-23538 Lübeck, Germany.

Defective heart valves are often replaced by implants in open-heart surgery. Both mechanical and biological implants are available. Among biological implants, xenograft ones-i.e., valves grafted from animals such as pigs, are widely used. Good implants should exhibit certain typical anatomical and functional characteristics to successfully replace the native tissue. Here, we describe a video-based system for measuring quality parameters of xenograft heart valve implants, including the area of the orifice and the fluttering of the valves' leaflets, i.e., their flaps (or cusps). Our system employs automatic methods that provide a precise and reproducible way to infer the quality of an implant. The automatic analysis of both a valve's orifice and the fluttering of its leaflets offers a more comprehensive quality assessment than current, mostly manual methods. We focus on valves with three leaflets, i.e., aortic, pulmonary, and tricuspid valves.
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http://dx.doi.org/10.1109/TBME.2008.2001290DOI Listing
December 2009

Directional view interpolation for compensation of sparse angular sampling in cone-beam CT.

IEEE Trans Med Imaging 2009 Jul 6;28(7):1011-22. Epub 2009 Jan 6.

Philips Research Europe-Aachen, 52066 Aachen, Germany.

In flat detector cone-beam computed tomography and related applications, sparse angular sampling frequently leads to characteristic streak artifacts. To overcome this problem, it has been suggested to generate additional views by means of interpolation. The practicality of this approach is investigated in combination with a dedicated method for angular interpolation of 3-D sinogram data. For this purpose, a novel dedicated shape-driven directional interpolation algorithm based on a structure tensor approach is developed. Quantitative evaluation shows that this method clearly outperforms conventional scene-based interpolation schemes. Furthermore, the image quality trade-offs associated with the use of interpolated intermediate views are systematically evaluated for simulated and clinical cone-beam computed tomography data sets of the human head. It is found that utilization of directionally interpolated views significantly reduces streak artifacts and noise, at the expense of small introduced image blur.
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http://dx.doi.org/10.1109/TMI.2008.2011550DOI Listing
July 2009

Multispectral filter-wheel cameras: geometric distortion model and compensation algorithms.

IEEE Trans Image Process 2008 Dec;17(12):2368-80

Institute of Imaging and Computer Vision, RWTH Aachen University, D-52056 Aachen, Germany.

Multispectral image acquisition considerably improves color accuracy in comparison to RGB technology. A common multispectral camera design concept features a filter-wheel consisting of six or more optical bandpass filters. By shifting the filters sequentially into the optical path, the electromagnetic spectrum is acquired through the channels, thus making an approximate reconstruction of the spectrum feasible. However, since the optical filters exhibit different thicknesses, refraction indices and may not be aligned in a perfectly coplanar manner, geometric distortions occur in each spectral channel: The reconstructed RGB images thus show rainbow-like color fringes. To compensate for these, we analyze the optical path and derive a mathematical model of the distortions. Based on this model we present two different algorithms for compensation and show that the color fringes vanish completely after application of our algorithms. We also evaluate our compensation algorithms in terms of accuracy and execution time.
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http://dx.doi.org/10.1109/TIP.2008.2006605DOI Listing
December 2008

Timing and targeting of cell-based VEGF165 gene expression in ischemic tissue.

J Surg Res 2009 Jan 13;151(1):153-62. Epub 2008 Mar 13.

Department of Plastic and Hand Surgery, Burn Care Center, University Clinics Witten/Herdecke, Campus Köln, Merheim, Germany.

Background: Therapeutic angiogenesis has become a key technology in experimental and clinical medicine. Only few data are available on the effects of timing and targeting of therapeutic proteins after cell-based gene transfer. This work investigates such effects after temporary expression of vascular endothelial growth factor 165 (VEGF(165)), the most commonly used angiogenic protein for therapeutic purposes.

Methods: We established a cell-based gene-transfer model using fibroblasts to temporarily produce VEGF(165). Cells were implanted into 40 rats. Protein expression and angiogenic effects were measured by PCR, immunohistology, and microangiography. To determine an improvement for survival of ischemically challenged tissue, cells were implanted in an ischemic flap model at different locations and time points.

Results: After implantation of modified cells, a temporary increase was found in the target tissue for VEGF(165), endothelial cell counts, and capillary network formations. Four wk later, histological alterations in the target tissue area were not different from controls. Implantation of modified cells into flap plus wound margin 1 wk before surgery showed significant improvement of tissue survival demonstrated by planimetric measurements and blood vessels counting in the target tissue.

Conclusion: In our model, temporary expression of VEGF(165) induces therapeutically relevant angiogenesis and improves blood supply only if applied 1 wk before ischemia. It is essential to include the surrounding area for induction of angiogenesis in this model. In contrast, the angiogenic effects are not effective in the target area and its surrounding tissue, if therapeutic gene expression is started during onset of ischemia or 2 wk before ischemia in this model.
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http://dx.doi.org/10.1016/j.jss.2008.01.038DOI Listing
January 2009

Computer-assisted diagnosis for early stage pleural mesothelioma: towards automated detection and quantitative assessment of pleural thickening from thoracic CT images.

Methods Inf Med 2007 ;46(3):324-31

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

Objectives: Pleural thickenings as biomarker of exposure to asbestos may evolve into malignant pleural mesothelioma. For its early stage, pleurectomy with perioperative treatment can reduce morbidity and mortality. The diagnosis is based on a visual investigation of CT images, which is a time-consuming and subjective procedure. Our aim is to develop an automatic image processing approach to detect and quantitatively assess pleural thickenings.

Methods: We first segment the lung areas, and identify the pleural contours. A convexity model is then used together with a Hounsfield unit threshold to detect pleural thickenings. The assessment of the detected pleural thickenings is based on a spline-based model of the healthy pleura.

Results: Tests were carried out on 14 data sets from three patients. In all cases, pleural contours were reliably identified, and pleural thickenings detected. PC-based Computation times were 85 min for a data set of 716 slices, 35 min for 401 slices, and 4 min for 75 slices, resulting in an average computation time of about 5.2 s per slice. Visualizations of pleurae and detected thickenings were provided.

Conclusion: Results obtained so far indicate that our approach is able to assist physicians in the tedious task of finding and quantifying pleural thickenings in CT data. In the next step, our system will undergo an evaluation in a clinical test setting using routine CT data to quantify its performance.
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http://dx.doi.org/10.1160/ME9050DOI Listing
July 2007

Towards fully automatic acquisition of multimodal cytopathological microscopy images with autofocus and scene managing.

Methods Inf Med 2007 ;46(3):314-23

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

Objectives: To increase the chance for a cure, cancer must be detected as early as possible. This can be achieved with cytopathological diagnostic methods. For a further increase of the diagnostic accuracy of these methods we introduced the multimodal cell analysis, viz, cells on the slide have to be relocalized to enable successive analysis of identical cells in different stains. For practical reasons the relocalization step must be automated.

Methods: For a fully automatic acquisition of successive cell images we use a passive autofocus that is adaptive to the material, i.e., to the cells, followed by a comparison of the scenes, i.e., the cell constellation, of two such obtained images from different stains. In case that no sub-scene match can be found the search is extended to the surrounding area. A set of 1556 scenes from seven specimens have been subject to our algorithm. The automatically relocalized and acquired images from a second stain have been manually compared to the images from a first stain.

Results: An overall relocalization rate of 85.4% is achieved. 14.3% of the images could not be relocalized and are lost for the following diagnostic process, while the critical case of erroneously matched images was observed in only 0.3% of cases.

Conclusions: We could show that it is possible to automatically acquire images of successive stains of identical cells on cytopathological specimens. The method presented achieves acceptable relocalization rates. Wrong image acquisitions are very rare and can mostly be ascribed to images with single cells, i.e., without scene information.
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http://dx.doi.org/10.1160/ME9049DOI Listing
July 2007

Ultrasound cerebral perfusion analysis based on a mathematical model for diminution harmonic imaging.

Methods Inf Med 2007 ;46(3):308-13

Institute for Signal Processing, Universität Lübeck, Lübeck, Germany.

Objectives: Cerebral vascular diseases are detect- able by CT/MRI-based methods. Drawbacks of these methods are that they are expensive, time-consuming and intolerable to critically ill patients. Ultrasound, as an inexpensive bedside method, promises to become an alternative. Among other harmonic imaging methods, the diminution harmonic imaging (DHI) method is known, which determines perfusion-related parameters by analyzing ultrasound contrast agent (UCA) diminution kinetics based on constant UCA infusion. The shortcoming of DHI is that the used mathematical model can only determine these parameters by least squares fitting the model onto the data.

Methods: In this work, the underlying mathematical model is further developed such that it becomes possible to directly calculate the parameters from the image data. Furthermore, the new model offers an improved way to estimate the spatial distribution of the destruction coefficient necessary for accurately determining the destruction power of the ultrasound pulse on the contrast agent.

Results: The direct calculation of the perfusion coefficient is much faster than the former fitting of the model. Perfusion as well as destruction coefficients are displayed as color-coded images. In an example, a region with perfusion deficits (as shown in a MR image of the same patient) is clearly identifiable.

Conclusions: Displaying the parameters as color-coded images facilitates result interpretation for the diagnosing physician. The results are preliminary and still have to be validated, but they suggest that the new DHI model improves the significance of ultrasound as a diagnostic help.
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http://dx.doi.org/10.1160/ME9048DOI Listing
July 2007

Analysis of superimposed oriented patterns.

IEEE Trans Image Process 2006 Dec;15(12):3690-700

Institute of Imaging and Computer Vision, RWTH Aachen University, 52062 Aachen, Germany.

Estimation of local orientation in images may be posed as the problem of finding the minimum gray-level variance axis in a local neighborhood. In bivariate images, the solution is given by the eigenvector corresponding to the smaller eigenvalue of a 2 x 2 tensor. For an ideal single orientation, the tensor is rank-deficient, i.e., the smaller eigenvalue vanishes. A large minimal eigenvalue signals the presence of more than one local orientation, what may be caused by non-opaque additive or opaque occluding objects, crossings, bifurcations, or corners. We describe a framework for estimating such superimposed orientations. Our analysis is based on the eigensystem analysis of suitably extended tensors for both additive and occluding superpositions. Unlike in the single-orientation case, the eigensystem analysis does not directly yield the orientations, rather, it provides so-called mixed-orientation parameters (MOPs). We, therefore, show how to decompose the MOPs into the individual orientations. We also show how to use tensor invariants to increase efficiency, and derive a new feature for describing local neighborhoods which is invariant to rigid transformations. Applications are, e.g., in texture analysis, directional filtering and interpolation, feature extraction for corners and crossings, tracking, and signal separation.
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http://dx.doi.org/10.1109/tip.2006.884921DOI Listing
December 2006

Ultrasound perfusion imaging in acute middle cerebral artery infarction predicts outcome.

Stroke 2004 May 18;35(5):1107-11. Epub 2004 Mar 18.

Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160 D-23538 Lübeck, Germany.

Background And Purpose: Initial reports indicate that transcranial harmonic imaging after ultrasound contrast agent bolus injection (BHI) can detect cerebral perfusion deficits in acute ischemic stroke. We evaluated parametric images of the bolus washout kinetics.

Methods: Twenty-three patients with acute internal carotid artery infarction were investigated with perfusion harmonic imaging after SonoVue bolus injection < or =40 hour after the onset of symptoms. The findings were compared with those of cranial computed tomography (CCT) and clinical course 4 months after stroke.

Results: Images of pixel-wise peak intensity (PPI) and time to peak intensity could be calculated for all patients. Spearman rank correlations of r=0.772 (P<0.001) and r=0.572 (P=0.008) between area of PPI signal decrease and area of infarction in the follow-up CCT as well as outcome after 4 months were obtained, respectively.

Conclusions: In the early phase of acute ischemic stroke, BHI after SonoVue bolus injection is a useful ultrasound tool for analyzing cerebral perfusion deficits at the patient's bedside. BHI data correlate with the definite area of infarction and outcome after 4 months.
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http://dx.doi.org/10.1161/01.STR.0000124125.19773.40DOI Listing
May 2004
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