Mouse models of non-alcoholic fatty liver disease (NAFLD) are required to define therapeutic targets, but detailed time-resolved studies to establish a sequence of events are lacking. Here, we fed male C57Bl/6N mice a Western or standard diet over 48 weeks. Multiscale time-resolved characterization was performed using RNA-seq, histopathology, immunohistochemistry, intravital imaging, and blood chemistry; the results were compared to human disease. Acetaminophen toxicity and ammonia metabolism were additionally analyzed as functional readouts. We identified a sequence of eight key events: formation of lipid droplets; inflammatory foci; lipogranulomas; zonal reorganization; cell death and replacement proliferation; ductular reaction; fibrogenesis; and hepatocellular cancer. Functional changes included resistance to acetaminophen and altered nitrogen metabolism. The transcriptomic landscape was characterized by two large clusters of monotonously increasing or decreasing genes, and a smaller number of ‘rest-and-jump genes’ that initially remained unaltered but became differentially expressed only at week 12 or later. Approximately 30% of the genes altered in human NAFLD are also altered in the present mouse model and an increasing overlap with genes altered in human HCC occurred at weeks 30–48. In conclusion, the observed sequence of events recapitulates many features of human disease and offers a basis for the identification of therapeutic targets.

Patient motion during medical imaging using techniques such as computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), or single emission computed tomography (SPECT) is well known to degrade images, leading to blurring effects or severe artifacts. Motion correction methods try to overcome these degrading effects. However, they need to be validated under realistic conditions. In this work, a sophisticated anthropomorphic thorax phantom is presented that combines several aspects of a simulator for cardio-respiratory motion. The phantom allows us to simulate various types of cardio-respiratory motions inside a human-like thorax, including features such as inflatable lungs, beating left ventricular myocardium, respiration-induced motion of the left ventricle, moving lung lesions, and moving coronary artery plaques. The phantom is constructed to be MR-compatible. This means that we can not only perform studies in PET, SPECT and CT, but also inside an MRI system. The technical features of the anthropomorphic thorax phantom Wilhelm are presented with regard to simulating motion effects in hybrid emission tomography and radiotherapy. This is supplemented by a study on the detectability of small coronary plaque lesions in PET/CT under the influence of cardio-respiratory motion, and a study on the accuracy of left ventricular blood volumes.

Purpose: To develop a flexible method for tracking respiratory and cardiac motions throughout MR and PET-MR body examinations that requires no additional hardware and minimal sequence modification. Methods: The incorporation of a contrast-neutral rosette navigator module following the RF excitation allows for robust cardiorespiratory motion tracking with minimal impact on the host sequence. Spatial encoding gradients are applied to the FID signal and the desired motion signals are extracted with a blind source separation technique. This approach is validated with an anthropomorphic, PET-MR-compatible motion phantom as well as in 13 human subjects. Results: Both respiratory and cardiac motions were reliably extracted from the proposed rosette navigator in phantom and patient studies. In the phantom study, the MR-derived motion signals were additionally validated against the ground truth measurement of diaphragm displacement and left ventricle model triggering pulse. Conclusion: The proposed method yields accurate respiratory and cardiac motion-state tracking, requiring only a short (1.76 ms) additional navigator module, which is self-refocusing and imposes minimal constraints on sequence design.

The SNR can serve as a general metric to assess the success of COM-based DDG, even in different scanners and patients. The derived formula for motion resolution can be used to estimate the actual motion extent reasonably well in cases of limited PET raw data statistics. This may be of interest for individualized radiotherapy treatment planning procedures of target structures subjected to respiratory motion.

PET attenuation correction for flexible MRI radio frequency surface coils in hybrid PET/MRI is still a challenging task, as position and shape of these coils conform to large inter-patient variabilities. The purpose of this feasibility study is to develop a novel method for the incorporation of attenuation information about flexible surface coils in PET reconstruction using the Microsoft Kinect V2 depth camera. The depth information is used to determine a dense point cloud of the coil's surface representing the shape of the coil. From a CT template-acquired once in advance-surface information of the coil is extracted likewise and converted into a point cloud. The two point clouds are then registered using a combination of an iterative-closest-point (ICP) method and a partially rigid registration step. Using the transformation derived through the point clouds, the CT template is warped and thereby adapted to the PET/MRI scan setup. The transformed CT template is converted into an attenuation map from Hounsfield units into linear attenuation coefficients. The resulting fitted attenuation map is then integrated into the MRI-based patient-specific DIXON-based attenuation map of the actual PET/MRI scan. A reconstruction of phantom PET data acquired with the coil present in the field-of-view (FoV), but without the corresponding coil attenuation map, shows large artifacts in regions close to the coil. The overall count loss is determined to be around 13% compared to a PET scan without the coil present in the FoV. A reconstruction using the new μ-map resulted in strongly reduced artifacts as well as increased overall PET intensities with a remaining relative difference of about 1% to a PET scan without the coil in the FoV.