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3D Ultrasound Computed Tomography (USCT) is an imaging method for early breast cancer detection. The third generation 3 USCT device is developed at Karlsruhe Institute of Technology. The USCT III device has a hemispherical transducer distribution and emits and receives nearly spherical waves. This enables reflection and transmission imaging simultaneously and fully in 3D. The main challenges for the front-end design are to integrate a large number of transducers, to allow high voltage coded excitation, and to receive low amplitude signals with high quality. These challenges were solved using a smart sensor frontend design with a custom application specific integrated circuit (ASIC).

Welcome and Introduction to SPIE Medical Imaging conference 11602: Ultrasonic Imaging and Tomography

Breast cancer is the most common cancer type among women. Approximately 40,000 women are expected to die from breast cancer every year. While digital mammography has a central role in the early diagnosis of breast cancer, many cancers are not visible in mammography, for example in women with dense breast tissue. Contrast enhanced magnetic resonance imaging (CE-MRI) of the breast is often used to detect lesions not visible in mammography. Lesions with suspicious characteristics on CE-MRI need to be further assessed with MRI-guided biopsy. However, MRI-guided biopsy is expensive, time consuming, and not widely available. In this paper, a novel method for a matching tool between MRI and spot mammograms is proposed. Our aim is to transfer information that is only visible in MRI onto mammographic spot projections, to enable X-ray guided biopsy even if the lesion is only visible in MRI. Two methods of registration in combination are used; a biomechanical model based registration between MRI and full view X-ray mammograms and a subsequent image based registration between full mammograms and spot mammograms. Preliminary results assessed for one patient from the Medical University of Vienna are presented. The target registration error (TRE) of biomechanical model based registration is 2.4 mm and the TRE of the image based registration is 9.5 mm. The total TRE of the two steps is 7.3 mm.

The time response of the ultrasound transducers used in our 3D ultrasound tomography device shows a slight reverberation. This may causes artifacts in the reconstructed images. Loss properties of materials used in the array fabrication have a big impact on their complex vibration behavior. Unfortunately, material parameters for accurate modeling are often not available in literature. Here, we present a method to derive loss properties of polymers and composites and how to include them in a finite element analysis (FEA). The method has three steps: First, an experiment to measure the frequency and thickness dependent sound attenuation. Second, a brute-force fit to a frequency-power law expression to obtain an analytic formulation. Third, a conversion of the sound attenuation to an equivalent structural loss factor. The last step is necessary as acoustic attenuation can not directly be implemented in structural mechanics FEA. We applied the method to derive loss properties of the filler and backing material which we use for our ultrasound transducer arrays. When including the loss factor in the simulation a reverberation is predicted, which matches the measurement well. Hence, considering loss properties allows more accurate modeling of complex vibration behavior. This aids in optimizing our ultrasound transducer array design towards better 3D ultrasound imaging.

Ultrasound computer tomography (USCT) is a promising modality for breast cancer diagnosis which images the reflectivity, sound speed and attenuation of tissue. Elastic properties of breast tissue, however, cannot directly be imaged although they have shown to be applicable as a discriminator between different tissue types. In this work we propose a novel approach combining USCT with the principles of strain elastography. Socalled USCT-SE makes use of imaging the breast in two deformation states, estimating the deformation field based on reconstructed images and thereby allows localizing and distinguishing soft and hard masses. We use a biomechanical model of the breast to realistically simulate both deformation states of the breast. The analysis of the strain is performed by estimating the deformation field from the deformed to the undeformed image by a non-rigid registration. In two experiments the non-rigid registration is applied to ground truth sound speed images and simulated SAFT images. Results of the strain analysis show that for both cases soft and hard lesions can be distinguished visually in the elastograms. This paper provides a first approach to obtain mechanical information based on external mechanical excitation of breast tissue in a USCT system.

Focused ultrasound (FUS) is a promising method to open the blood brain barrier (BBB) for treatment of neurodegenerative diseases. Accurate targeting is essential for a successful BBB opening (BBBo). We aim to develop a robust therapy planning for BBBo in mice, which is challenging due to the size of the brain and the influence of the skull on the ultrasound pressure distribution. For enabling mouse individual therapy planning, a simulation tool is proposed, developed and validated. We used the k-Wave toolbox to enable 3D acoustic simulations of the commercial FUS system from Image Guided Therapy (IGT). Micro-CT scans were used to model the geometry of skulls. Simulations using a mouse skull showed an attenuation of approx. 20–24% depending on the position of penetration, which was validated by hydrophone measurements in the same range. Based on these validations we planned BBBo in m ice by placing the transducer at different positions over the mouse brain and varying the excitation amplitude. With different transducer positions, the peak pressure in the brain varied between 0.54 MPa and 0.62 MPa at 11% output level, which is expected to enable safe BBBo. Subsequently, in vivo experiments were conducted using the aforementioned simulation parameters. BBBo was confirmed by contrast enhanced T1 weighted magnetic resonance images immediately after sonication.

Conventional iterative methods for image reconstruction in ultrasound transmission tomography need to perform many iterations where at each iteration one has to compute the complex forward model of ultrasound wave propagation, and hence they are time-consuming. We use a U-net neural network to accelerate the reconstruction, by training the network to map from an initial reconstruction obtained via a few iterations of L-BFGS method to the target ground truth image. Since the computation of a forward pass of the neural network is very fast, we can expect a significant acceleration using the trained network for image reconstruction. Experiments show that our trained network can replace 40 L-BFGS iterations to generate equivalent reconstructions with slightly better quantitative quality in terms of normalized root mean square error and better visual quality due to the network's denoising effect. It can achieve up to 283× speedup compared with L-BFGS method for reconstructing small-size sound speed images with 80×80 pixels. This implies that we can expect even greater acceleration effects when applying such approach to reconstruct large-size 3D images.

A semi-automated packaging process for transducer array manufacturing is presented. As an major innovation, a transducer disc is integrated in a sandwich structure between a printed circuit board (PCB) and an acoustic matching layer. Each of the transducer discs contains 18 lead-zirconium-titanate (PZT) fibres embedded in epoxy. To interconnect the transducer array components, adhesive bonding and automatic pick-and-place processes were used. A pre-series was evaluated by measuring the electro-mechanical impedance (EMI) before and after the assembly. Statistical analysis showed consistent behaviour of the series resonance f s and the electro-mechanical coupling k eff before and after the packaging. This encouraged the manufacturing of 256 arrays. These arrays will now be integrated in an ultrasound computer tomography (USCT) system with 3D scanning aperture for breast cancer imaging. With this system, we intend to bridge the gap towards clinical use of full 3D USCT.

The requirements of our third generation 3D ultrasound computer tomography system (USCT) led to a transducer array design based on single-fibre piezocomposites. The used piezoelectric ceramic fibres exhibit a thickness to diameter ratio of 4/3. This ratio results in a proximity of the dominant axial and lateral vibration resonances. The standard Krimholtz-Leedom-Matthaei (KLM) model considers only one spatial dimension. This limits the validity of the modelled predictions for our application. By adding a coupled transmission line in series to the axial resonator, the standard model can be extended to take additional spatial dimensions into account. Using model parameters from literature resulted in a low model-to-measurement fit. To enhance the prediction accuracy, a brute-force optimisation over four model parameters was conducted. With the optimal parameter set, a fit of 90.3% could finally be achieved. The necessary model parameter changes were found reasonable for the piezocomposite design. With the presented model enhancement it is now possible to consider both dominant vibration modes of our transducers.

Ultrasound transmission tomography is a promising modality for breast cancer diagnosis. For image reconstruc- tion approximations to the acoustic wave equation such as straight or bent rays are commonly used due to their low computational complexity. For sparse apertures the coverage of the volume by rays is very limited, thereby requiring strong regularization in the inversion process. The concept of fat rays reduces the sparseness and includes the contributions to the measured signal originating from the first Fresnel zone. In this work we investi- gate the application of the fat ray concept to ultrasound transmission tomography. We implement a straight ray, bent ray and fat ray forward model. For the inversion process a least squares solver (LSQR), a simultaneous al- gebraic reconstruction technique (SART) and a compressive sensing based total variation minimization (TVAL3) is applied. The combination of forward models and inversion processes has been evaluated by synthetic data. TVAL3 outperforms SART and LSQR, especially for sparse apertures. The fat ray concept is able to decrease the error with respect to the ground truth compared to the bent ray method especially for SART and LSQR inversion, and especially for very sparse apertures.

A 3D ultrasound computer tomography (USCT) device with a nearly isotropic and spatially invariant 3D point spread function has been constructed at Institute for Data Processing and Electronic (IPE), Karlsruhe Institute of Technology (KIT). This device is currently applied in clinical studies for breast cancer screening. In this paper, a new method to develop an automated segmentation algorithm for USCT acquired images is proposed. The method employs distance regularized level set evolutionary (DRLSE) active contours along with surface fitting extrapolation and 3D binary mask generation for fully automatic segmentation outcome. In the first stage of the proposed algorithm, DRLSE is applied to those 3D USCT slice images which contain breast and are less affected by noise and ring artifacts named as Cat2. The DRLSE segmentation results are employed to extrapolate the rest of slice images known as Cat1. To overcome defectively segmented slice images, a 3D binary mask is generated out of USCT attenuation images. The 3D binary mask is multiplied by the DRLSE-based segmentation results to form finally segmented 3D USCT images. The method was tested on 12 clinical dataset images. According to F-measure criterion, the proposed method shows higher performance than the previously proposed semiautomatic segmentation one.

A promising candidate for improved imaging of breast cancer is ultrasound computer tomography (USCT). Current experimental USCT systems are still focused in elevation dimension resulting in a large slice thickness, limited depth of field, loss of out-of-plane reflections, and a large number of movement steps to acquire a stack of images. 3D USCT emitting and receiving spherical wave fronts overcomes these limitations. We built an optimized 3D USCT, realizing for the first time the full benefits of a 3D system. The point spread function could be shown to be nearly isotropic in 3D, to have very low spatial variability and fit the predicted values. The contrast of the phantom images is very satisfactory in spite of imaging with a sparse aperture. The resolution and imaged details of the reflectivity reconstruction are comparable to a 3 T MRI volume. Important for the obtained resolution are the simultaneously obtained results of the transmission tomography. The KIT 3D USCT was then tested in a pilot study on ten patients. The primary goals of the pilot study were to test the USCT device, the data acquisition protocols, the image reconstruction methods and the image fusion techniques in a clinical environment. The study was conducted successfully; the data acquisition could be carried out for all patients with an average imaging time of six minutes per breast. The reconstructions provide promising images. Overlaid volumes of the modalities show qualitative and quantitative information at a glance. This paper gives a summary of the involved techniques, methods, and first results.

A promising candidate for sensitive imaging of breast cancer is 3D Ultrasound Computer Tomography (3D USCT). So far its clinical applicability for diagnosis has been limited by the duration of the demanding image reconstruction. In this paper we investigate how signal processing and image reconstruction can be accelerated for diagnosis by using heterogeneous hardware. Additionally, the time and costs for real-time system for a future diagnosis and therapy device is estimated. Reusing the device's built-in FPGA-based data acquisition system (DAQ) through reconfiguration results in a speed-up by a factor of 7 for signal processing and by a factor of 2 for image reconstruction. Applying cutting-edge single FPGAs and GPUs, speed-ups by a factor of 10 (FPGA) and 6 (GPU) for signal processing and 15 (FPGA) and 37 (GPU) for image reconstruction were achieved compared to a recent quad-core Intel Core-i7 CPU. Using quad-core CPUs and a cluster of eight GPUs allowed us for the first time to calculate volumes in less than 30 min with an overall speed-up by a factor of 47, enabling a first clinical study. Based on these results we extrapolated that real-time reconstruction for a therapeutic 3D USCT will be possible in the year 2020 if the trend in density follows the ITRS roadmap.

Synthetic-aperture (SA) imaging is a popular method to visualize the reflectivity of an object from ultrasonic reflections. The method yields an image of the (volume) contrast in acoustic impedance with respect to the embedding. Typically, constant mass density is assumed in the underlying derivation. Due to the band-limited nature of the recorded data, the image is blurred in space, which is quantified by the associated point spread function. SA volume imaging is valid under the Born approximation, where it is assumed that the contrast is weak. When objects are large with respect to the wavelength, it is questionable whether SA volume imaging should be the method-of-choice. Herein, we propose an alternative solution that we refer to as SA interface imaging. This approach yields a vector image of the discontinuities of acoustic impedance at the tissue interfaces. Constant wave speed is assumed in the underlying derivation. The image is blurred in space by a tensor, which we refer to as the interface spread function. SA interface imaging is valid under the Kirchhoff approximation, where it is assumed that the wavelength is small compared to the spatial dimensions of the interfaces. We compare the performance of volume and interface imaging on synthetic data and on experimental data of a gelatin cylinder with a radius of 75 wavelengths, submerged in water. As expected, the interface image peaks at the gelatin-water interface, while the volume image exposes a peak and trough on opposing sides of the interface.

Increasing interest in multimodal breast cancer diagnosis has led to the development of methods for MRI to X-ray mammography registration. The severe breast deformation in X-ray mammography is often tackled by biomechanical models, yet there is no common consensus in literature about the required complexity of the deformation model and the simulation strategy. We present for the first time an automated patient-specific biomechanical model based image registration of MRI to digital breast tomosynthesis (DBT). DBT provides three-dimensional information of the compressed breast and as such drives the registration by a volume similarity metric. We compare different simulation strategies and propose a patient-specific optimization of simulation and model parameters. The average three-dimensional breast overlap measured by Dice coefficient of DBT and registered MRI improves for four analyzed subjects by including the estimation of unloaded state, simulation of gravity, and a concentrated pull force that mimics manual positioning of the breast on the plates from 88.1% for a mere compression simulation to 93.1% when including all our proposed simulation steps, whereas additional parameter optimization further increased the value to 94.4%.

Increasing interest in multimodal breast cancer diagnosis has led to the development of methods for MRI to X-ray mammography registration to provide direct correlation of modalities. The severe breast deformation in X-ray mammography is often tackled by biomechanical models, which however have not yet brought the registration accuracy to a clinically applicable level. We present a novel registration approach of MRI to X-ray tomosynthesis. Tomosynthesis provides three-dimensional information of the compressed breast and as such has the ability to open new possibilities in the registration of MRI and X-ray data. By bundling the 3D information from the tomosynthesis volume with the 2D projection images acquired at different measuring angles, we provide a correlation between the registration error in 3D and 2D and evaluate different 3D- and 2D-based similarity metrics to drive the optimization of the automated patient-specific registration approach. From the preliminary study of four analysed patients we found that the projected registration error is in general larger than the 3D error in case of small registration errors in the cranio-caudal direction. Although both image shape and intensitybased 2D similarity metrics showed a clear correlation with the 2D registration error at different projection angles, metrics that relied on the combined 2D and 3D information yielded in most of the cases the minimal registration error and as such had better performance than similarity metrics that rely only on the shape similarity of volumes.

In Ultrasound computer tomography (USCT) Synthetic aperture focusing technique (SAFT) is often applied for reflectivity image reconstruction. Phase aberration correction is essential to cope with the large sound speed differences in water and the different human tissues. In this paper we compare two approaches for phase aberration correction: a straight ray approximation using the Bresenham algorithm (B-SAFT) and a bent ray approximating using a multi-stencil Fast Marching Method (FMM-SAFT). The analysis is carried out with simulated point scatterers and simulated phantoms to measure the effect on the image resolution and contrast. The method is additionally applied to experimental data. B-SAFT degrades the image resolution and contrast in cases of large sound speed differences of objects and if the reconstructed point is close to a boundary where a change in impedance is present. FMM-SAFT is able to recover the image quality in these cases if the sound speed distribution is known accurately and with high resolution. If these requirements cannot be met, B-SAFT proved to be more robust.

Ultrasound Computer Tomography (USCT) is a promising breast imaging modality under development. Comparison to a standard method like mammography is essential for further development. Due to significant differences in image dimensionality and compression state of the breast, correlating USCT images and X-ray mammograms is challenging. In this paper we present a 2D/3D registration method to improve the spatial correspondence and allow direct comparison of the images. It is based on biomechanical modeling of the breast and simulation of the mammographic compression. We investigate the effect of including patient-specific material parameters estimated automatically from USCT images. The method was systematically evaluated using numerical phantoms and in-vivo data. The average registration accuracy using the automated registration was 11.9mm. Based on the registered images a method for analysis of the diagnostic value of the USCT images was developed and initially applied to analyze sound speed and attenuation images based on X-ray mammograms as ground truth. Combining sound speed and attenuation allows differentiating lesions from surrounding tissue. Overlaying this information on mammograms, combines quantitative and morphological information for multimodal diagnosis.

An airborne ultrasound imaging system was developed for reflection tomography. The ultrasound transducers surround the region of interest (ROI) in an arrangement optimized for maximum coverage and homogeneous distributed image quality. In this work, we developed a workflow for automatic segmentation and classification of objects in the reconstructed images. Our workflow can be applied for varying intensities of object edges with a local maxima based segmentation and a multi-parameter image reconstruction. The segmented regions are classified with a neural network, and the object localization was implemented with Generalized Hough Transform using a custom template for each classified object in the data set. A classification accuracy of 95% for six trained test objects and a localization accuracy of 5 mm were achieved.

Ultrasound Computer Tomography (USCT) is a promising new imaging system for breast cancer diagnosis. An essential step before further processing is to remove the water background from the reconstructed images. In this paper we present a fully-automated image segmentation method based on three-dimensional active contours. The active contour method is extended by applying gradient vector flow and encoding the USCT aperture characteristics as additional weighting terms. A surface detection algorithm based on a ray model is developed to initialize the active contour, which is iteratively deformed to capture the breast outline in USCT reflection images. The evaluation with synthetic data showed that the method is able to cope with noisy images, and is not influenced by the position of the breast and the presence of scattering objects within the breast. The proposed method was applied to 14 in-vivo images resulting in an average surface deviation from a manual segmentation of 2.7 mm. We conclude that automated segmentation of USCT reflection images is feasible and produces results comparable to a manual segmentation. By applying the proposed method, reproducible segmentation results can be obtained without manual interaction by an expert.

Synthetic Aperture Focusing Technique (SAFT) allows fast data acquisition and optimally focused images. The computational burden for 3D imaging is large as for each voxel the delay for each acquired A-scan has to be calculated, e.g. O(N5) for N3 voxels and N2 A-scans. For 3D reconstruction of objects which are large in terms of the wavelength, e.g. ≥ (100 λ)3, the computation of one volume takes several days on a current multicore PC. If the 3D distribution of the speed of sound is applied to correct the delays, the computation time increases further. In this work a time of flight interpolation based GPU implementation (TOFI-SAFT) is presented which accelerates our previous GPU implementation of speed of sound corrected SAFT by a factor of 7 to 16 min. with only minor reduction of image quality.

Computer aided diagnosis (CAD) of breast cancer is mainly focused on monomodal applications. Here we present a fully automated multimodal CAD, which uses patient-specific image registration of MRI and two-view X-ray mammography. The image registration estimates the spatial correspondence between each voxel in the MRI and each pixel in cranio-caudal and mediolateral-oblique mammograms. Thereby we can combine features from both modalities. As a proof of concept we classify fixed regions of interest (ROI) into normal and suspect tissue. We investigate the classification performance of the multimodal classification in several setups against a classification with MRI features only. The average sensitivity of detecting suspect ROIs improves by approximately 2% when combining MRI with both mammographic views compared to MRI-only detection, while the specificity stays at a constant level. We conclude that automatically combining MRI and X-ray can enhance the result of a breast CAD system.

Airborne ultrasonic sensors are widely used in industry for detecting movement of targets and measuring their distances to the sensor. More complex object localization is usually done with optical systems, yet their application is limited. In this work an airborne ultrasound imaging system is developed, which reconstructs an image of the region-of-interest (ROI) with multiple objects. With further image processing, this system allows more sophisticated object localization. The proposed optimization method results in a sensor system with minimum number of sensors and improved sensor distribution for maximum coverage of the ROI and homogeneous performance.

For iterative image reconstruction of transmission tomography we apply the paraxial approximation of the Helmholtz equation for a spherical transducer arrangement. We choose this approach due to its three order of magnitude lower complexity than full wave solutions with the same precision for transmission tomography. In homogeneous media we prove that our forward solution is exact. With the help of this forward solution 2D and 3D ultrasound measurements could be simulated for transmission tomography. 2D reconstructions of a breast-like numerical phantom had a deviation in sound speed of 0.14 m/s and a deviation in attenuation of 6.5% from the ground truth. Applications up to now are breast cancer diagnostics and non-destructive testing.

A promising candidate for breast cancer imaging is ultrasound computer tomography (USCT). At Karlsruhe Institute of Technology (KIT) a 3D USCT with a semiellipsoidal aperture consisting of several hundreds of US transducers was built. The utilized imaging methods require accurate and reliable temperature information over the measured space and acquisition time. Several methods were applied which improved the temperature accuracy and reliability beyond the hardware defaults by one order of magnitude from ±1°C to approx. 0.005°C beyond the requirement of 0.1°C.

In our first clinical study with a full 3D Ultrasound Computer Tomography (USCT) system patient data was acquired in eight minutes for one breast. In this paper the patient movement during the acquisition was analyzed quantitatively and as far as possible corrected in the resulting images. The movement was tracked in ten successive reflectivity reconstructions of full breast volumes acquired during 10 s intervals at different aperture positions, which were separated by 41 s intervals. The mean distance between initial and final position was 2.2 mm (standard deviation (STD) ± 0.9 mm, max. 4.1 mm, min. 0.8 mm) and the average sum of all moved distances was 4.9 mm (STD ± 1.9 mm, max. 8.8 mm, min. 2.7 mm). The tracked movement was corrected by summing successive images, which were transformed according to the detected movement. The contrast of these images increased and additional image content became visible.