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Book ; Online: End-to-end Learning for Image-based Detection of Molecular Alterations in Digital Pathology

Teichmann, Marvin / Aichert, Andre / Bohnenberger, Hanibal / Ströbel, Philipp / Heimann, Tobias

2022

Abstract: Current approaches for classification of whole slide images (WSI) in digital pathology predominantly utilize a two-stage learning pipeline. The first stage identifies areas of interest (e.g. tumor tissue), while the second stage processes cropped tiles ... ...

Abstract	Current approaches for classification of whole slide images (WSI) in digital pathology predominantly utilize a two-stage learning pipeline. The first stage identifies areas of interest (e.g. tumor tissue), while the second stage processes cropped tiles from these areas in a supervised fashion. During inference, a large number of tiles are combined into a unified prediction for the entire slide. A major drawback of such approaches is the requirement for task-specific auxiliary labels which are not acquired in clinical routine. We propose a novel learning pipeline for WSI classification that is trainable end-to-end and does not require any auxiliary annotations. We apply our approach to predict molecular alterations for a number of different use-cases, including detection of microsatellite instability in colorectal tumors and prediction of specific mutations for colon, lung, and breast cancer cases from The Cancer Genome Atlas. Results reach AUC scores of up to 94% and are shown to be competitive with state of the art two-stage pipelines. We believe our approach can facilitate future research in digital pathology and contribute to solve a large range of problems around the prediction of cancer phenotypes, hopefully enabling personalized therapies for more patients in future. Comment: MICCAI 2022; 8.5 Pages, 4 Figures
Keywords	Computer Science - Computer Vision and Pattern Recognition ; Electrical Engineering and Systems Science - Image and Video Processing ; Quantitative Biology - Quantitative Methods
Subject code	004
Publishing date	2022-06-30
Publishing country	us
Document type	Book ; Online
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Article ; Online: Calibration-free beam hardening reduction in x-ray CBCT using the epipolar consistency condition and physical constraints.

Würfl, Tobias / Hoffmann, Mathis / Aichert, André / Maier, Andreas K / Maaß, Nicole / Dennerlein, Frank

Medical physics

2020 Volume 46, Issue 12, Page(s) e810–e822

Abstract: Background: The beam hardening effect is a typical source of artifacts in x-ray cone beam computed tomography (CBCT). It causes streaks in reconstructions and corrupted Hounsfield units toward the center of objects, widely known as cupping artifacts.: ...

Abstract	Background: The beam hardening effect is a typical source of artifacts in x-ray cone beam computed tomography (CBCT). It causes streaks in reconstructions and corrupted Hounsfield units toward the center of objects, widely known as cupping artifacts. Purpose: We present a novel efficient projection data-based method for reduction of beam-hardening artifacts and incorporate physical constraints on the shape of the compensation functions. The method is calibration-free and requires no additional knowledge of the scanning setup. Method: The mathematical model of the beam hardening effect caused by a single material is analyzed. We show that the effect of beam hardening on the resulting functions on the line integral measurements are monotonous and concave functions of the ideal data. This holds irrespective of any limiting assumptions on the energy dependency of the material, the detector response or properties of the x-ray source. A regression model for the beam hardening effect respecting these theoretical restrictions is proposed. Subsequently, we present an efficient method to estimate the parameters of this model directly in projection domain using an epipolar consistency condition. Computational efficiency is achieved by exploiting the linearity of an intermediate function in the formulation of our optimization problem. Results: Our evaluation shows that the proposed physically constrained ECC Conclusions: The combination of mathematical consistency condition and a compensation model that is based on the properties of x-ray physics enables us to improve image quality of measured data retrospectively and to decrease the need for calibration in a data-driven manner.
MeSH term(s)	Artifacts ; Cone-Beam Computed Tomography ; Image Processing, Computer-Assisted/methods ; Models, Theoretical
Language	English
Publishing date	2020-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	188780-4
ISSN	2473-4209 ; 0094-2405
ISSN (online)	2473-4209
ISSN	0094-2405
DOI	10.1002/mp.13625
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Article ; Online: Consistency-based respiratory motion estimation in rotational angiography.

Unberath, Mathias / Aichert, André / Achenbach, Stephan / Maier, Andreas

Medical physics

2017 Volume 44, Issue 9, Page(s) e113–e124

Abstract: Purpose: Rotational coronary angiography enables 3D reconstruction but suffers from intra-scan cardiac and respiratory motion. While gating handles cardiac motion, respiratory motion requires compensation. State-of-the-art algorithms rely on 3D-2D ... ...

Abstract	Purpose: Rotational coronary angiography enables 3D reconstruction but suffers from intra-scan cardiac and respiratory motion. While gating handles cardiac motion, respiratory motion requires compensation. State-of-the-art algorithms rely on 3D-2D registration that depends on initial reconstructions of sufficient quality. We propose a compensation method that is applied directly in projection domain. It overcomes the need for reconstruction and thus complements the state-of-the-art. Methods: Virtual single-frame background subtraction based on vessel segmentation and spectral deconvolution yields non-truncated images of the contrasted lumen. This allows motion compensation based on data consistency conditions. We compensate craniocaudal shifts by optimizing epipolar consistency to (a) devise an image-based surrogate for cardiac motion and (b) compensate for respiratory motion. We validate our approach in two numerical phantom studies and three clinical cases. Results: Correlation of the image-based surrogate for cardiac motion with the ECG-based ground truth was excellent yielding a Pearson correlation of 0.93 ± 0.04. Considering motion compensation, the target error measure decreased by 98% and 69%, respectively, for the phantom experiments while for the clinical cases the same figure of merit improved by 46 ± 21%. Conclusions: The proposed method is entirely image-based and accurately estimates craniocaudal shifts due to respiration and cardiac contraction. Future work will investigate experimental trajectories and possibilities for simplification of the single-frame subtraction pipeline.
MeSH term(s)	Algorithms ; Artifacts ; Coronary Angiography ; Humans ; Imaging, Three-Dimensional ; Motion ; Movement ; Phantoms, Imaging
Language	English
Publishing date	2017-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	188780-4
ISSN	2473-4209 ; 0094-2405
ISSN (online)	2473-4209
ISSN	0094-2405
DOI	10.1002/mp.12021
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Article ; Online: Prior-Free Respiratory Motion Estimation in Rotational Angiography.

Unberath, Mathias / Taubmann, Oliver / Aichert, Andre / Achenbach, Stephan / Maier, Andreas

IEEE transactions on medical imaging

2018 Volume 37, Issue 9, Page(s) 1999–2009

Abstract: Rotational coronary angiography using C-arm angiography systems enables intra-procedural 3-D imaging that is considered beneficial for diagnostic assessment and interventional guidance. Despite previous efforts, rotational angiography was not yet ... ...

Abstract	Rotational coronary angiography using C-arm angiography systems enables intra-procedural 3-D imaging that is considered beneficial for diagnostic assessment and interventional guidance. Despite previous efforts, rotational angiography was not yet successfully established in clinical practice for coronary artery procedures due to challenges associated with substantial intra-scan respiratory and cardiac motion. While gating handles cardiac motion during reconstruction, respiratory motion requires compensation. State-of-the-art algorithms rely on 3-D / 2-D registration that requires an uncompensated reconstruction of sufficient quality. To overcome this limitation, we investigate two prior-free respiratory motion estimation methods based on the optimization of: 1) epipolar consistency conditions (ECCs) and 2) a task-based auto-focus measure (AFM). The methods assess redundancies in projection images or impose favorable properties of 3-D space, respectively, and are used to estimate the respiratory motion of the coronary arteries within rotational angiograms. We evaluate our algorithms on the publicly available CAVAREV benchmark and on clinical data. We quantify reductions in error due to respiratory motion compensation using a dedicated reconstruction domain metric. Moreover, we study the improvements in image quality when using an analytic and a novel temporal total variation regularized algebraic reconstruction algorithm. We observed substantial improvement in all figures of merit compared with the uncompensated case. Improvements in image quality presented as a reduction of double edges, blurring, and noise. Benefits of the proposed corrections were notable even in cases suffering little corruption from respiratory motion, translating to an improvement in the vessel sharpness of (6.08 ± 4.46)% and (14.7 ± 8.80)% when the ECC-based and the AFM-based compensation were applied. On the CAVAREV data, our motion compensation approach exhibits an improvement of (27.6 ± 7.5)% and (97.0 ± 17.7)% when the ECC and AFM were used, respectively. At the time of writing, our method based on AFM is leading the CAVAREV scoreboard. Both motion estimation strategies are purely image-based and accurately estimate the displacements of the coronary arteries due to respiration. While current evidence suggests the superior performance of AFM, future work will further investigate the use of ECC in the context of angiography as they solely rely on geometric calibration and projection-domain images.
MeSH term(s)	Algorithms ; Angiography, Digital Subtraction/methods ; Coronary Angiography/methods ; Humans ; Imaging, Three-Dimensional/methods ; Phantoms, Imaging
Language	English
Publishing date	2018-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	622531-7
ISSN	1558-254X ; 0278-0062
ISSN (online)	1558-254X
ISSN	0278-0062
DOI	10.1109/TMI.2018.2806310
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Book ; Online: Anatomy of a superorganism -- structure and growth dynamics of army ant bivouacs

Bochynek, Thomas / Schiffers, Florian / Aichert, André / Cossairt, Oliver / Garnier, Simon / Rubenstein, Michael

2021

Abstract: Beyond unicellular and multicellular organisms, there is a third type of structural complexity in living animals: that of the mechanical self-assembly of groups of distinct multicellular organisms into dynamical, functional structures. One of the most ... ...

Abstract	Beyond unicellular and multicellular organisms, there is a third type of structural complexity in living animals: that of the mechanical self-assembly of groups of distinct multicellular organisms into dynamical, functional structures. One of the most striking examples of such structures is the army ant bivouac, a nest which self-assembles solely from the interconnected bodies of hundreds of thousands of individuals. These bivouacs are difficult to study because they rapidly disassemble when disturbed, and hence little is known about the structure and rules that individuals follow during their formation. Here we use a custom-built Computed Tomography scanner to investigate the details of the internal structure and growth process of army ant bivouacs. We show that bivouacs are heterogeneous structures, which throughout their growth maintain a thick shell surrounding a less dense interior that contains empty spaces akin to nest chambers. We find that ants within the bivouac do not carry more than approximately eight times their weight regardless of the size of the structure or their position within it. This observation suggests that bivouac size is not limited by physical constraints of the ants' morphology. This study brings us closer to understanding the rules used by individuals to govern the formation of these exceptional superorganismal structures, and provides insight into how to create engineered self-assembling systems with, for instance, swarms of robots or active matter.
Keywords	Quantitative Biology - Quantitative Methods
Subject code	612
Publishing date	2021-10-18
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Disassemblable Fieldwork CT Scanner Using a 3D-printed Calibration Phantom

Schiffers, Florian / Bochynek, Thomas / Aichert, Andre / Würfl, Tobias / Rubenstein, Michael / Cossairt, Oliver

2020

Abstract: The use of computed tomography (CT) imaging has become of increasing interest to academic areas outside of the field of medical imaging and industrial inspection, e.g., to biology and cultural heritage research. The pecularities of these fields, however, ...

Abstract	The use of computed tomography (CT) imaging has become of increasing interest to academic areas outside of the field of medical imaging and industrial inspection, e.g., to biology and cultural heritage research. The pecularities of these fields, however, sometimes require that objects need to be imaged on-site, e.g., in field-work conditions or in museum collections. Under these circumstances, it is often not possible to use a commercial device and a custom solution is the only viable option. In order to achieve high image quality under adverse conditions, reliable calibration and trajectory reproduction are usually key requirements for any custom CT scanning system. Here, we introduce the construction of a low-cost disassemblable CT scanner that allows calibration even when trajectory reproduction is not possible due to the limitations imposed by the project conditions. Using 3D-printed in-image calibration phantoms, we compute a projection matrix directly from each captured X-ray projection. We describe our method in detail and show successful tomographic reconstructions of several specimen as proof of concept. Comment: This paper was originally published at the 6th International Conference on Image Formation in X-Ray Computed Tomography (CTmeeting 2020)
Keywords	Electrical Engineering and Systems Science - Image and Video Processing ; Computer Science - Computer Vision and Pattern Recognition ; Physics - Instrumentation and Detectors
Publishing date	2020-11-12
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: An Improved Extrapolation Scheme for Truncated CT Data Using 2D Fourier-Based Helgason-Ludwig Consistency Conditions.

Xia, Yan / Berger, Martin / Bauer, Sebastian / Hu, Shiyang / Aichert, Andre / Maier, Andreas

International journal of biomedical imaging

2017 Volume 2017, Page(s) 1867025

Abstract: We improve data extrapolation for truncated computed tomography (CT) projections by using Helgason-Ludwig (HL) consistency conditions that mathematically describe the overlap of information between projections. First, we theoretically derive a 2D Fourier ...

Abstract	We improve data extrapolation for truncated computed tomography (CT) projections by using Helgason-Ludwig (HL) consistency conditions that mathematically describe the overlap of information between projections. First, we theoretically derive a 2D Fourier representation of the HL consistency conditions from their original formulation (projection moment theorem), for both parallel-beam and fan-beam imaging geometry. The derivation result indicates that there is a zero energy region forming a double-wedge shape in 2D Fourier domain. This observation is also referred to as the Fourier property of a sinogram in the previous literature. The major benefit of this representation is that the consistency conditions can be efficiently evaluated via 2D fast Fourier transform (FFT). Then, we suggest a method that extrapolates the truncated projections with data from a uniform ellipse of which the parameters are determined by optimizing these consistency conditions. The forward projection of the optimized ellipse can be used to complete the truncation data. The proposed algorithm is evaluated using simulated data and reprojections of clinical data. Results show that the root mean square error (RMSE) is reduced substantially, compared to a state-of-the-art extrapolation method.
Language	English
Publishing date	2017-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2196721-0
ISSN	1687-4196 ; 1687-4188
ISSN (online)	1687-4196
ISSN	1687-4188
DOI	10.1155/2017/1867025
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Article: Image-based tracking of the teeth for orthodontic augmented reality.

Aichert, André / Wein, Wolfgang / Ladikos, Alexander / Reichl, Tobias / Navab, Nassir

Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention

2012 Volume 15, Issue Pt 2, Page(s) 601–608

Abstract: We present image-based methods for tracking teeth in a video image with respect to a CT scan of the jaw, in order to enable a novel light-weight augmented reality (AR) system in orthodontistry. Its purpose is guided bracket placement in orthodontic ... ...

Abstract	We present image-based methods for tracking teeth in a video image with respect to a CT scan of the jaw, in order to enable a novel light-weight augmented reality (AR) system in orthodontistry. Its purpose is guided bracket placement in orthodontic correction. In this context, our goal is to determine the position of the patient maxilla and mandible in a video image solely based on a CT scan. This is suitable for image guidance through an overlay of the video image with the planned position of brackets in a monocular AR system. Our tracking algorithm addresses the contradicting requirements of robustness, accuracy and performance in two problem-specific formulations. First, we exploit a distance-based modulation of two iso-surfaces from the CT image to approximate the appearance of the gum line. Second, back-projection of previous video frames to an iso-surface is used to account for recently placed brackets. In combination, this novel algorithm allowed us to track several sequences of three patient videos of real procedures, despite difficult lighting conditions. Paired with a systematic evaluation, we were able to show practical feasibility of such a system.
MeSH term(s)	Humans ; Orthodontic Brackets ; Pattern Recognition, Automated/methods ; Prosthesis Implantation/methods ; Radiographic Image Enhancement/methods ; Radiographic Image Interpretation, Computer-Assisted/methods ; Radiography, Dental/methods ; Reproducibility of Results ; Sensitivity and Specificity ; Tomography, X-Ray Computed/methods ; User-Computer Interface
Language	English
Publishing date	2012-12-18
Publishing country	Germany
Document type	Journal Article
DOI	10.1007/978-3-642-33418-4_74
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Article ; Online: Epipolar Consistency in Transmission Imaging.

Aichert, André / Berger, Martin / Wang, Jian / Maass, Nicole / Doerfler, Arnd / Hornegger, Joachim / Maier, Andreas K

IEEE transactions on medical imaging

2015 Volume 34, Issue 11, Page(s) 2205–2219

Abstract: This paper presents the derivation of the Epipolar Consistency Conditions (ECC) between two X-ray images from the Beer-Lambert law of X-ray attenuation and the Epipolar Geometry of two pinhole cameras, using Grangeat's theorem. We motivate the use of ... ...

Abstract	This paper presents the derivation of the Epipolar Consistency Conditions (ECC) between two X-ray images from the Beer-Lambert law of X-ray attenuation and the Epipolar Geometry of two pinhole cameras, using Grangeat's theorem. We motivate the use of Oriented Projective Geometry to express redundant line integrals in projection images and define a consistency metric, which can be used, for instance, to estimate patient motion directly from a set of X-ray images. We describe in detail the mathematical tools to implement an algorithm to compute the Epipolar Consistency Metric and investigate its properties with detailed random studies on both artificial and real FD-CT data. A set of six reference projections of the CT scan of a fish were used to evaluate accuracy and precision of compensating for random disturbances of the ground truth projection matrix using an optimization of the consistency metric. In addition, we use three X-ray images of a pumpkin to prove applicability to real data. We conclude, that the metric might have potential in applications related to the estimation of projection geometry. By expression of redundancy between two arbitrary projection views, we in fact support any device or acquisition trajectory which uses a cone-beam geometry. We discuss certain geometric situations, where the ECC provide the ability to correct 3D motion, without the need for 3D reconstruction.
MeSH term(s)	Algorithms ; Animals ; Fishes ; Imaging, Three-Dimensional/methods ; Models, Theoretical ; Movement/physiology ; Phantoms, Imaging ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2015-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	622531-7
ISSN	1558-254X ; 0278-0062
ISSN (online)	1558-254X
ISSN	0278-0062
DOI	10.1109/TMI.2015.2426417
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Article: Interactive 3D visualization of a single-view X-ray image.

Wieczorek, Matthias / Aichert, André / Fallavollita, Pascal / Kutter, Oliver / Ahmadi, Ahmad / Wang, Lejing / Navab, Nassir

Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention

2011 Volume 14, Issue Pt 1, Page(s) 73–80

Abstract: In this paper, we present an interactive X-Ray perceptual visualization technique (IXPV) to improve 3D perception in standard single-view X-Ray images. Based on a priori knowledge from CT data, we re-introduce lost depth information into the original ... ...

Abstract	In this paper, we present an interactive X-Ray perceptual visualization technique (IXPV) to improve 3D perception in standard single-view X-Ray images. Based on a priori knowledge from CT data, we re-introduce lost depth information into the original single-view X-Ray image without jeopardizing information of the original X-Ray. We propose a novel approach that is suitable for correct fusion of intraoperative X-Ray and ultrasound, co-visualization of X-Ray and surgical tools, and for improving the 3D perception of standard radiographs. Phantom and animal cadaver datasets were used during experimentation to demonstrate the impact of our technique. Results from a questionnaire completed by 11 clinicians and computer scientists demonstrate the added value of introduced depth cues directly in an X-Ray image. In conclusion, we propose IXPV as a futuristic alternative to the standard radiographic image found in today's clinical setting.
MeSH term(s)	Algorithms ; Animals ; Cadaver ; Equipment Design ; Humans ; Image Processing, Computer-Assisted/methods ; Imaging, Three-Dimensional/methods ; Models, Statistical ; Phantoms, Imaging ; Radiometry/methods ; Reproducibility of Results ; Software ; Tomography, X-Ray Computed/methods ; X-Rays
Language	English
Publishing date	2011-10-15
Publishing country	Germany
Document type	Journal Article
DOI	10.1007/978-3-642-23623-5_10
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