Multidrug and toxin extrusion 2 (MATE2-K (SLC47A2)), a polyspecific organic cation exporter, facilitates the renal elimination of the antidiabetes drug metformin. In this study, we characterized genetic variants of MATE2-K, determined their association with metformin response, and elucidated their impact by means of a comparative protein structure model. Four nonsynonymous variants and four variants in the MATE2-K basal promoter region were identified from ethnically diverse populations. Two nonsynonymous variants—c.485C>T and c.1177G>A—were shown to be associated with significantly lower metformin uptake and reduction in protein expression levels. MATE2-K basal promoter haplotypes containing the most common variant, g.−130G>A (>26% allele frequency), were associated with a significant increase in luciferase activities and reduced binding to the transcriptional repressor myeloid zinc finger 1 (MZF-1). Patients with diabetes who were homozygous for g.−130A had a significantly poorer response to metformin treatment, assessed as relative change in glycated hemoglobin (HbA1c) (−0.027 (−0.076, 0.033)), as compared with carriers of the reference allele, g.−130G (−0.15 (−0.17, −0.13)) (P = 0.002). Our study showed that MATE2-K plays a role in the antidiabetes response to metformin.

As a common software framework, CONRAD enables the medical physics community to share algorithms and develop new ideas. In particular this offers new opportunities for scientific collaboration and quantitative performance comparison between the methods of different groups.

Purpose: A C-arm CT system has been shown to be capable of scanning a single cadaver leg under loaded conditions by virtue of its highly flexible acquisition trajectories. In Part I of this study, using the 4D XCAT-based numerical simulation, the authors predicted that the involuntary motion in the lower body of subjects in weight-bearing positions would seriously degrade image quality and the authors suggested three motion compensation methods by which the reconstructions could be corrected to provide diagnostic image quality. Here, the authors demonstrate that a flat-panel angiography system is appropriate for scanning both legs of subjects in vivo under weight-bearing conditions and further evaluate the three motion-correction algorithms using in vivo data. Methods: The geometry of a C-arm CT system for a horizontal scan trajectory was calibrated using the PDS-2 phantom. The authors acquired images of two healthy volunteers while lying supine on a table, standing, and squatting at several knee flexion angles. In order to identify the involuntary motion of the lower body, nine 1-mm-diameter tantalum fiducial markers were attached around the knee. The static mean marker position in 3D, a reference for motion compensation, was estimated by back-projecting detected markers in multiple projections using calibrated projection matrices and identifying the intersection points in 3D of the back-projected rays. Motion was corrected using three different methods (described in detail previously): (1) 2D projection shifting, (2) 2D deformable projection warping, and (3) 3D rigid body warping. For quantitative image quality analysis, SSIM indices for the three methods were compared using the supine data as a ground truth. Results: A 2D Euclidean distance-based metric of subjects' motion ranged from 0.85 mm (±0.49 mm) to 3.82 mm (±2.91 mm) (corresponding to 2.76 to 12.41 pixels) resulting in severe motion artifacts in 3D reconstructions. Shifting in 2D, 2D warping, and 3D warping improved the SSIM in the central slice by 20.22%, 16.83%, and 25.77% in the data with the largest motion among the five datasets (SCAN5); improvement in off-center slices was 18.94%, 29.14%, and 36.08%, respectively. Conclusions: The authors showed that C-arm CT control can be implemented for nonstandard horizontal trajectories which enabled us to scan and successfully reconstruct both legs of volunteers in weight-bearing positions. As predicted using theoretical models, the proposed motion correction methods improved image quality by reducing motion artifacts in reconstructions; 3D warping performed better than the 2D methods, especially in off-center slices.

The authors showed that their method based on the NGI similarity measure yields reconstruction quality close to the MB reference method. In contrast to the MB method, the proposed method does not require any preparation prior to the examination which will improve the clinical workflow and patient comfort. Further, the authors found that the MB method causes small, nonrigid deformations at the bone outline which indicates that markers may not accurately reflect the internal motion close to the knee joint. Therefore, the authors believe that the proposed method is a promising alternative to MB motion management.

In this paper, we consider the use of prior knowledge within neural networks. In particular, we investigate the effect of a known transform within the mapping from input data space to the output domain. We demonstrate that use of known transforms is able to change maximal error bounds.In order to explore the effect further, we consider the problem of X-ray material decomposition as an example to incorporate additional prior knowledge. We demonstrate that inclusion of a non-linear function known from the physical properties of the system is able to reduce prediction errors therewith improving prediction quality from SSIM values of 0.54 to 0.88. This approach is applicable to a wide set of applications in physics and signal processing that provide prior knowledge on such transforms. Also maximal error estimation and network understanding could be facilitated within the context of precision learning.

Purpose: Human subjects in standing positions are apt to show much more involuntary motion than in supine positions. The authors aimed to simulate a complicated realistic lower body movement using the four-dimensional (4D) digital extended cardiac-torso (XCAT) phantom. The authors also investigated fiducial marker-based motion compensation methods in two-dimensional (2D) and threedimensional (3D) space. The level of involuntary movement-induced artifacts and image quality improvement were investigated after applying each method. Methods: An optical tracking system with eight cameras and seven retroreflective markers enabled us to track involuntary motion of the lower body of nine healthy subjects holding a squat position at 60• of flexion. The XCAT-based knee model was developed using the 4D XCAT phantom and the optical tracking data acquired at 120 Hz. The authors divided the lower body in the XCAT into six parts and applied unique affine transforms to each so that the motion (6 degrees of freedom) could be synchronized with the optical markers' location at each time frame. The control points of the XCAT were tessellated into triangles and 248 projection images were created based on intersections of each ray and monochromatic absorption. The tracking data sets with the largest motion (Subject 2) and the smallest motion (Subject 5) among the nine data sets were used to animate the XCAT knee model. The authors defined eight skin control points well distributed around the knees as pseudofiducial markers which functioned as a reference in motion correction. Motion compensation was done in the following ways: (1) simple projection shifting in 2D, (2) deformable projection warping in 2D, and (3) rigid body warping in 3D. Graphics hardware accelerated filtered backprojection was implemented and combined with the three correction methods in order to speed up the simulation process. Correction fidelity was evaluated as a function of number of markers used (4-12) and marker distribution in three scenarios. Results: Average optical-based translational motion for the nine subjects was 2.14 mm (±0.69 mm) and 2.29 mm (±0.63 mm) for the right and left knee, respectively. In the representative central slices of Subject 2, the authors observed 20.30%, 18.30%, and 22.02% improvements in the structural similarity (SSIM) index with 2D shifting, 2D warping, and 3D warping, respectively. The performance of 2D warping improved as the number of markers increased up to 12 while 2D shifting and 3D warping were insensitive to the number of markers used. The minimum required number of markers for 2D shifting, 2D warping, and 3D warping was 4-6, 12, and 8, respectively. An even distribution of markers over the entire field of view provided robust performance for all three correction methods. Conclusions:The authors were able to simulate subject-specific realistic knee movement in weightbearing positions. This study indicates that involuntary motion can seriously degrade the image quality. The proposed three methods were evaluated with the...

Purpose Benefiting from multi‐energy x‐ray imaging technology, material decomposition facilitates the characterization of different materials in x‐ray imaging. However, the performance of material decomposition is limited by the accuracy of the decomposition model. Due to the presence of nonideal effects in x‐ray imaging systems, it is difficult to explicitly build the imaging system models for material decomposition. As an alternative, this paper explores the feasibility of using machine learning approaches for material decomposition tasks. Methods In this work, we propose a learning‐based pipeline to perform material decomposition. In this pipeline, the step of feature extraction is implemented to integrate more informative features, such as neighboring information, to facilitate material decomposition tasks, and the step of hold‐out validation with continuous interleaved sampling is employed to perform model evaluation and selection. We demonstrate the material decomposition capability of our proposed pipeline with promising machine learning algorithms in both simulation and experimentation, the algorithms of which are artificial neural network (ANN), Random Tree, REPTree and Random Forest. The performance was quantitatively evaluated using a simulated XCAT phantom and an anthropomorphic torso phantom. In order to evaluate the proposed method, two measurement‐based material decomposition methods were used as the reference methods for comparison studies. In addition, deep learning‐based solutions were also investigated to complete this work as a comprehensive comparison of machine learning solution for material decomposition. Results In both the simulation study and the experimental study, the introduced machine learning algorithms are able to train models for the material decomposition tasks. With the application of neighboring information, the performance of each machine learning algorithm is strongly improved. Compared to the state‐of‐the‐art method, the performance of ANN in the simulation study is an improvement of over 24% in the noiseless scenarios and over 169% in the noisy scenario, while the performance of the Random Forest is an improvement of over 40% and 165%, respectively. Similarly, the performance of ANN in the experimental study is an improvement of over 42% in the denoised scenario and over 45% in the original scenario, while the performance of Random Forest is an improvement by over 33% and 40%, respectively. Conclusions The proposed pipeline is able to build generic material decomposition models for different scenarios, and it was validated by quantitative evaluation in both simulation and experimentation. Compared to the reference methods, appropriate features and machine learning algorithms can significantly improve material decomposition performance. The results indicate that it is feasible and promising to perform material decomposition using machine learning methods, and our study will facilitate future efforts toward clinical applications.

Abstract:Osteoarthritis is a degenerative disease affecting bones and cartilage especially in the human knee. In this context, cartilage thickness is an indicator for knee cartilage health. Thickness measurements are performed on medical images acquired in-vivo. Currently, there is no standard method agreed upon that defines a distance measure in articular cartilage. In this work, we present a comparison of different methods commonly used in literature. These methods are based on nearest neighbors, surface normal vectors, local thickness and potential field lines. All approaches were applied to manual segmentations of tibia and lateral and medial tibial cartilage performed by experienced raters. The underlying data were contrast agent-enhanced cone-beam C-arm CT reconstructions of one healthy subject's knee. The subject was scanned three times, once in supine position and two times in a standing weight-bearing position. A comparison of the resulting thickness maps shows similar distributions and high correlation coefficients between the approaches above 0.90. The nearest neighbor method results on average in the lowest cartilage thickness values, while the local thickness approach assigns the highest values. We showed that the different methods agree in their thickness distribution. The results will be used for a future evaluation of cartilage change under weight-bearing conditions.