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For image-guided small animal irradiations, the whole workflow of imaging, organ contouring, irradiation planning, and delivery is typically performed in a single session requiring continuous administration of anaesthetic agents. Automating contouring leads to a faster workflow, which limits exposure to anaesthesia and thereby, reducing its impact on experimental results and on animal wellbeing. Here, we trained the 2D and 3D U-Net architectures of no-new-Net (nnU-Net) for autocontouring of the thorax in mouse micro-CT images. We trained the models only on native CTs and evaluated their performance using an independent testing dataset (i.e., native CTs not included in the training and validation). Unlike previous studies, we also tested the model performance on an external dataset (i.e., contrast-enhanced CTs) to see how well they predict on CTs completely different from what they were trained on. We also assessed the interobserver variability using the generalized conformity index ( CI gen ) among three observers, providing a stronger human baseline for evaluating automated contours than previous studies. Lastly, we showed the benefit on the contouring time compared to manual contouring. The results show that 3D models of nnU-Net achieve superior segmentation accuracy and are more robust to unseen data than 2D models. For all target organs, the mean surface distance (MSD) and the Hausdorff distance (95p HD) of the best performing model for this task (nnU-Net 3d_fullres) are within 0.16 mm and 0.60 mm, respectively. These values are below the minimum required contouring accuracy of 1 mm for small animal irradiations, and improve significantly upon state-of-the-art 2D U-Net-based AIMOS method. Moreover, the conformity indices of the 3d_fullres model also compare favourably to the interobserver variability for all target organs, whereas the 2D models perform poorly in this regard. Importantly, the 3d_fullres model offers 98% reduction in contouring time.

With the wide access to studies of selected gene expressions in transgenic animals, mice have become the dominant species as cerebral disease models. Many of these studies are performed on animals of not more than eight weeks, declared as adult animals. Based on the earlier reports that full brain maturation requires at least three months in rats, there is a clear need to discern the corresponding minimal animal age to provide an “adult brain” in mice in order to avoid modulation of disease progression/therapy studies by ongoing developmental changes. For this purpose, we have studied anatomical brain alterations of mice during their first six months of age. Using T2-weighted and diffusion-weighted MRI, structural and volume changes of the brain were identified and compared with histological analysis of myelination. Mouse brain volume was found to be almost stable already at three weeks, but cortex thickness kept decreasing continuously with maximal changes during the first three months. Myelination is still increasing between three and six months, although most dramatic changes are over by three months. While our results emphasize that mice should be at least three months old when adult animals are needed for brain studies, preferred choice of one particular metric for future investigation goals will result in somewhat varying age windows of stabilization. •Mouse brain volume is already stable at three weeks of age.•Mouse brain cortex continues to flatten till three months of age.•Myelination in mouse brain still increases till three months of age.•Mice need to be three months or older, when brain studies are to be done on adult animals.

Pulmonary embolism (PE) is a life-threatening condition requiring prompt diagnosis and treatment. Visual assessment of computed tomographic pulmonary angiography (CTPA) is the first-choice diagnostic tool. New imaging biomarkers could provide additional prognostic information for improved risk stratification. We hypothesized in this exploratory study, that contrast enhancement patterns in the aorta may contain such information. CTPA scans of 93 acute PE patients were analyzed retrospectively. Firstly, the aorta was segmented automatically by TotalSegmentator and its centerline was extracted. Subsequently, lines were fitted on intensities within a region of interest perpendicularly to the aorta centerline, from which three parameters were extracted: mean intensity, proximal intensity and contrast gradient. After confounder analysis, logistic regression with forward selection evaluated the predictive value of these parameters for 12 adverse outcomes (six short-term and six long-term). Lung volume, aorta dimension and contrast delay were considered as possible confounders but were not selected by forward selection. Logistic regression (n = 93) showed that a less steep contrast gradient (decreasing by 10 Hounsfield unit/%) was associated with a reduction in odds of the following short-term adverse outcomes: 48.1% for intensive care unit admission (odds ratio [OR] = 0.519, 95% confidence interval [CI]: 0.306-0.804), 29.3% for oxygen therapy >24 hours (OR = 0.707, 95% CI: 0.496-0.976), 60.6% for reperfusion therapy (OR = 0.394, 95% CI: 0.178-0.682), 57.5% for vasopressor therapy (OR = 0.425, 95% CI: 0.194-0.741), and 50.2% for PE-related death (OR = 0.498, 95% CI: 0.246-0.915). No significant associations were found with long-term outcomes. The aorta contrast gradient, automatically quantified from CTPA, is a relevant adjunctive predictor for short-term outcomes in PE patients. Long-term outcomes, however, could not be predicted by aorta measurement. This pilot study provides initial insights into predictive value of aorta enhancement, stimulating further exploration with external data.

Visual scoring of interstitial lung disease in systemic sclerosis (SSc-ILD) from CT scans is laborious, subjective and time-consuming. This study aims to develop a deep learning framework to automate SSc-ILD scoring. The automated framework is a cascade of two neural networks. The first network selects the craniocaudal positions of the five scoring levels. Subsequently, for each level, the second network estimates the ratio of three patterns to the total lung area: the total extent of disease (TOT), ground glass (GG) and reticulation (RET). To overcome the score imbalance in the second network, we propose a method to augment the training dataset with synthetic data. To explain the network’s output, a heat map method is introduced to highlight the candidate interstitial lung disease regions. The explainability of heat maps was evaluated by two human experts and a quantitative method that uses the heat map to produce the score. The results show that our framework achieved a κ of 0.66, 0.58, and 0.65, for the TOT, GG and RET scoring, respectively. Both experts agreed with the heat maps in 91%, 90% and 80% of cases, respectively. Therefore, it is feasible to develop a framework for automated SSc-ILD scoring, which performs competitively with human experts and provides high-quality explanations using heat maps. Confirming the model’s generalizability is needed in future studies.

State-of-the-art fluoroscopic knee kinematic analysis methods require the patient-specific bone shapes segmented from CT or MRI. Substituting the patient-specific bone shapes with personalizable models, such as statistical shape models (SSM), could eliminate the CT/MRI acquisitions, and thereby decrease costs and radiation dose (when eliminating CT). SSM based kinematics, however, have not yet been evaluated on clinically relevant joint motion parameters. Therefore, in this work the applicability of SSMs for computing knee kinematics from biplane fluoroscopic sequences was explored. Kinematic precision with an edge based automated bone tracking method using SSMs was evaluated on 6 cadaveric and 10 in-vivo fluoroscopic sequences. The SSMs of the femur and the tibia–fibula were created using 61 training datasets. Kinematic precision was determined for medial–lateral tibial shift, anterior–posterior tibial drawer, joint distraction–contraction, flexion, tibial rotation and adduction. The relationship between kinematic precision and bone shape accuracy was also investigated. The SSM based kinematics resulted in sub-millimeter (0.48–0.81mm) and approximately 1° (0.69–0.99°) median precision on the cadaveric knees compared to bone-marker-based kinematics. The precision on the in-vivo datasets was comparable to that of the cadaveric sequences when evaluated with a semi-automatic reference method. These results are promising, though further work is necessary to reach the accuracy of CT-based kinematics. We also demonstrated that a better shape reconstruction accuracy does not automatically imply a better kinematic precision. This result suggests that the ability of accurately fitting the edges in the fluoroscopic sequences has a larger role in determining the kinematic precision than that of the overall 3D shape accuracy.

The shape and distribution of vascular lesions in pulmonary embolism (PE) and chronic thromboembolic pulmonary hypertension (CTEPH) are different. We investigated whether automated quantification of pulmonary vascular morphology and densitometry in arteries and veins imaged by computed tomographic pulmonary angiography (CTPA) could distinguish PE from CTEPH. We analyzed CTPA images from a cohort of 16 PE patients, 6 CTEPH patients, and 15 controls. Pulmonary vessels were extracted with a graph‐cut method, and separated into arteries and veins using deep‐learning classification. Vascular morphology was quantified by the slope (α) and intercept (β) of the vessel radii distribution. To quantify lung perfusion defects, the median pulmonary vascular density was calculated. By combining these measurements with densities measured in parenchymal areas, pulmonary trunk, and descending aorta, a static perfusion curve was constructed. All separate quantifications were compared between the three groups. No vascular morphology differences were detected in contrast to vascular density values. The median vascular density (interquartile range) was −567 (113), −452 (95), and −470 (323) HU, for the control, PE, and CTEPH group. The static perfusion curves showed different patterns between groups, with a statistically significant difference in aorta‐pulmonary trunk gradient between the PE and CTEPH groups (p = 0.008). In this proof of concept study, not vasculature morphology but densities differentiated between patients of three groups. Further technical improvements are needed to allow for accurate differentiation between PE and CTEPH, which in this study was only possible statistically by measuring the density gradient between aorta and pulmonary trunk.

In recent years, machine learning approaches have been successfully applied to the field of neuroimaging for classification and regression tasks. However, many approaches do not give an intuitive relation between the raw features and the diagnosis. Therefore, they are difficult for clinicians to interpret. Moreover, most approaches treat the features extracted from the brain (for example, voxelwise gray matter concentration maps from brain MRI) as independent variables and ignore their spatial and anatomical relations. In this paper, we present a new Support Vector Machine (SVM)-based learning method for the classification of Alzheimer's disease (AD), which integrates spatial-anatomical information. In this way, spatial-neighbor features in the same anatomical region are encouraged to have similar weights in the SVM model. Secondly, we introduce a group lasso penalty to induce structure sparsity, which may help clinicians to assess the key regions involved in the disease. For solving this learning problem, we use an accelerated proximal gradient descent approach. We tested our method on the subset of ADNI data selected by Cuingnet et al. (2011) for Alzheimer's disease classification, as well as on an independent larger dataset from ADNI. Good classification performance is obtained for distinguishing cognitive normals (CN) vs. AD, as well as on distinguishing between various sub-types (e.g. CN vs. Mild Cognitive Impairment). The model trained on Cuignet's dataset for AD vs. CN classification was directly used without re-training to the independent larger dataset. Good performance was achieved, demonstrating the generalizability of the proposed methods. For all experiments, the classification results are comparable or better than the state-of-the-art, while the weight map more clearly indicates the key regions related to Alzheimer's disease. [Display omitted]

Nonrigid image registration is an important, but time-consuming task in medical image analysis. In typical neuroimaging studies, multiple image registrations are performed, i.e., for atlas-based segmentation or template construction. Faster image registration routines would therefore be beneficial. In this paper we explore acceleration of the image registration package elastix by a combination of several techniques: (i) parallelization on the CPU, to speed up the cost function derivative calculation; (ii) parallelization on the GPU building on and extending the OpenCL framework from ITKv4, to speed up the Gaussian pyramid computation and the image resampling step; (iii) exploitation of certain properties of the B-spline transformation model; (iv) further software optimizations. The accelerated registration tool is employed in a study on diagnostic classification of Alzheimer's disease and cognitively normal controls based on T1-weighted MRI. We selected 299 participants from the publicly available Alzheimer's Disease Neuroimaging Initiative database. Classification is performed with a support vector machine based on gray matter volumes as a marker for atrophy. We evaluated two types of strategies (voxel-wise and region-wise) that heavily rely on nonrigid image registration. Parallelization and optimization resulted in an acceleration factor of 4-5x on an 8-core machine. Using OpenCL a speedup factor of 2 was realized for computation of the Gaussian pyramids, and 15-60 for the resampling step, for larger images. The voxel-wise and the region-wise classification methods had an area under the receiver operator characteristic curve of 88 and 90%, respectively, both for standard and accelerated registration. We conclude that the image registration package elastix was substantially accelerated, with nearly identical results to the non-optimized version. The new functionality will become available in the next release of elastix as open source under the BSD license.

Longitudinal studies on brain pathology and assessment of therapeutic strategies rely on a fully mature adult brain to exclude confounds of cerebral developmental changes. Thus, knowledge about onset of adulthood is indispensable for discrimination of developmental phase and adulthood. We have performed a high-resolution longitudinal MRI study at 11.7T of male Wistar rats between 21days and six months of age, characterizing cerebral volume changes and tissue-specific myelination as a function of age. Cortical thickness reaches final value at 1month, while volume increases of cortex, striatum and whole brain end only after two months. Myelin accretion is pronounced until the end of the third postnatal month. After this time, continuing myelination increases in cortex are still seen on histological analysis but are no longer reliably detectable with diffusion-weighted MRI due to parallel tissue restructuring processes. In conclusion, cerebral development continues over the first three months of age. This is of relevance for future studies on brain disease models which should not start before the end of month 3 to exclude serious confounds of continuing tissue development. •Longitudinal rat brain development from 21 days to 6 months with high resolution MRI.•Brain volume is a better criteria for maturation than cortex thickness.•DTI allows to monitor myelination maturation in this life phase.•DTI and histology indicate rat brain maturation is not complete till 3 months of age.•Caution for ongoing brain maturation processes during rodent brain disease studies.

Artificial intelligence techniques, specifically deep learning, have already affected daily life in a wide range of areas. Likewise, initial applications have been explored in rheumatology. Deep learning might not easily surpass the accuracy of classic techniques when performing classification or regression on low-dimensional numerical data. With images as input, however, deep learning has become so successful that it has already outperformed the majority of conventional image-processing techniques developed during the past 50 years. As with any new imaging technology, rheumatologists and radiologists need to consider adapting their arsenal of diagnostic, prognostic and monitoring tools, and even their clinical role and collaborations. This adaptation requires a basic understanding of the technical background of deep learning, to efficiently utilize its benefits but also to recognize its drawbacks and pitfalls, as blindly relying on deep learning might be at odds with its capabilities. To facilitate such an understanding, it is necessary to provide an overview of deep-learning techniques for automatic image analysis in detecting, quantifying, predicting and monitoring rheumatic diseases, and of currently published deep-learning applications in radiological imaging for rheumatology, with critical assessment of possible limitations, errors and confounders, and conceivable consequences for rheumatologists and radiologists in clinical practice.Deep learning is a powerful technique with great potential for the analysis and interpretation of rheumatological images. To successfully use deep learning, rheumatologists should understand the tasks involved in image processing and the potential confounders and limitations that can affect the analysis of clinical data.