Sinusoidal endothelial cells and mesenchymal CXCL12-abundant reticular cells are principal bone marrow stromal components, which critically modulate haematopoiesis at various levels, including haematopoietic stem cell maintenance. These stromal subsets are thought to be scarce and function via highly specific interactions in anatomically confined niches. Yet, knowledge on their abundance, global distribution and spatial associations remains limited. Using three-dimensional quantitative microscopy we show that sinusoidal endothelial and mesenchymal reticular subsets are remarkably more abundant than estimated by conventional flow cytometry. Moreover, both cell types assemble in topologically complex networks, associate to extracellular matrix and pervade marrow tissues. Through spatial statistical methods we challenge previous models and demonstrate that even in the absence of major specific interaction forces, virtually all tissue-resident cells are invariably in physical contact with, or close proximity to, mesenchymal reticular and sinusoidal endothelial cells. We further show that basic structural features of these stromal components are preserved during ageing.

Abstract-Spatial regularization is essential in image registration, which is an ill-posed problem. Regularization can help to avoid both physically implausible displacement fields and local minima during optimization. Tikhonov regularization (squared 2-norm) is unable to correctly represent non-smooth displacement fields, that can, for example, occur at sliding interfaces in the thorax and abdomen in image time-series during respiration. In this paper, isotropic Total Variation (TV) regularization is used to enable accurate registration near such interfaces. We further develop the TV-regularization for parametric displacement fields and provide an efficient numerical solution scheme using the Alternating Directions Method of Multipliers (ADMM). The proposed method was successfully applied to four clinical databases which capture breathing motion, including CT lung and MR liver images. It provided accurate registration results for the whole volume. A key strength of our proposed method is that it does not depend on organ masks that are conventionally required by many algorithms to avoid errors at sliding interfaces. Furthermore, our method is robust to parameter selection, allowing the use of the same parameters for all tested databases. The average target registration error (TRE) of our method is superior (10% to 40%) to other techniques in the literature. It provides precise motion quantification and sliding detection with sub-pixel accuracy on the publicly available breathing motion databases (mean TREs of 0.95 mm for DIR 4D CT, 0.96 mm for DIR COPDgene, 0.91 mm for POPI databases).

Congenital or posttraumatic bone deformity may lead to reduced range of motion, joint instability, pain, and osteoarthritis. The conventional joint-preserving therapy for such deformities is corrective osteotomy-the anatomical reduction or realignment of bones with fixation. In this procedure, the bone is cut and its fragments are correctly realigned and stabilized with an implant to secure their position during bone healing. Corrective osteotomy is an elective procedure scheduled in advance, providing sufficient time for careful diagnosis and operation planning. Accordingly, computer-based methods have become very popular for its preoperative planning. These methods can improve precision not only by enabling the surgeon to quantify deformities and to simulate the intervention preoperatively in three dimensions, but also by generating a surgical plan of the required correction. However, generation of complex surgical plans is still a major challenge, requiring sophisticated techniques and profound clinical expertise. In addition to preoperative planning, computer-based approaches can also be used to support surgeons during the course of interventions. In particular, since recent advances in additive manufacturing technology have enabled cost-effective production of patient-and intervention-specific osteotomy instruments, customized interventions can thus be planned for and performed using such instruments. In this chapter, state of the art and future perspectives of computer-assisted deformity-correction surgery of the upper and lower extremities are presented. We elaborate on the benefits and pitfalls of different approaches based on our own experience in treating over 150 patients with three-dimensional preoperative planning and patient-specific instrumentation.

Despite many uses of ultrasound, some pathologies such as breast cancer still cannot reliably be diagnosed in either conventional B-mode ultrasound imaging nor with more recent ultrasound elastography methods. Speed-of-sound (SoS) is a quantitative imaging biomarker, which is sensitive to structural changes due to pathology, and hence could facilitate diagnosis. Full-angle Ultrasound Computed Tomography (USCT) was proposed to obtain spatially-resolved SoS images, however, its water-bath setup involves practical limitations. To increase clinical utility and for widespread use, recently, a limited-angle Fourier-domain SoS reconstruction was proposed, however, it suffers from significant image reconstruction artifacts. In this work, we present a SoS reconstruction strategy, where the forward problem is formulated using differential time-of-flight measurements based on apparent displacements along different ultrasound wave propagation paths, and the inverse problem is solved in spatial-domain using a proposed total-variation scheme with spatially-varying anisotropic weighting to compensate for geometric bias from limited angle imaging setup. This is shown to be robust to missing displacement data and easily allow for incorporating any prior geometric information. In numerical simulations, SoS values in inclusions are accurately reconstructed with 90% accuracy up to a noise level of 50%. With respect to Fourier-domain reconstruction, our proposed method improved contrast ratio from 0.37 to 0.67 for even high noise levels such as 50%. Numerical fullwave simulation and our preliminary in-vivo results illustrate the clinical applicability of our method in a breast cancer imaging setting. Our proposed method requires single-sided access to the tissue and can be implemented as an add-on to conventional ultrasound equipment, applicable to a range of transducers and applications.

Variations in the shape and appearance of anatomical structures in medical images are often relevant radiological signs of disease. Automatic tools can help automate parts of this manual process. A cloud-based evaluation framework is presented in this paper including results of benchmarking current state-of-the-art medical imaging algorithms for anatomical structure segmentation and landmark detection: the VISCERAL Anatomy benchmarks. The algorithms are implemented in virtual machines in the cloud where participants can only access the training data and can be run privately by the benchmark administrators to objectively compare their performance in an unseen common test set. Overall, 120 computed tomography and magnetic resonance patient volumes were manually annotated to create a standard Gold Corpus containing a total of 1295 structures and 1760 landmarks. Ten participants contributed with automatic algorithms for the organ segmentation task, and three for the landmark localization task. Different algorithms obtained the best scores in the four available imaging modalities and for subsets of anatomical structures. The annotation framework, resulting data set, evaluation setup, results and performance analysis from the three VISCERAL Anatomy benchmarks are presented in this article. Both the VISCERAL data set and Silver Corpus generated with the fusion of the participant algorithms on a larger set of non-manually-annotated medical images are available to the research community.