Mechanical constraints imposed by 3D cellular geometry and arrangement modulate growth patterns in the Arabidopsis embryo

Morphogenesis occurs in 3D space over time and is guided by coordinated gene expression programs. Here we use postembryonic development in Arabidopsis plants to investigate the genetic control of growth. We demonstrate that gene expression driving the production of the growth-stimulating hormone gibberellic acid and downstream growth factors is first induced within the radicle tip of the embryo. The center of cell expansion is, however, spatially displaced from the center of gene expression. Because the rapidly growing cells have very different geometry from that of those at the tip, we hypothesized that mechanical factors may contribute to this growth displacement. To this end we developed 3D finite-element method models of growing custom-designed digital embryos at cellular resolution. We used this framework to conceptualize how cell size, shape, and topology influence tissue growth and to explore the interplay of geometrical and genetic inputs into growth distribution. Our simulations showed that mechanical constraints are sufficient to explain the disconnect between the experimentally observed spatiotemporal patterns of gene expression and early postembryonic growth. The center of cell expansion is the position where genetic and mechanical facilitators of growth converge. We have thus uncovered a mechanism whereby 3D cellular geometry helps direct where genetically specified growth takes place.

Patient-specific spinal stiffness in AIS: a preoperative and noninvasive method.

INTRODUCTION The clinical tests currently used to assess spinal biomechanics preoperatively are unable to assess true mechanical spinal stiffness. They rely on spinal displacement without considering the force required to deform a patient's spine. We propose a preoperative method for noninvasively quantifying the three-dimensional patient-specific stiffness of the spines of adolescent idiopathic scoliosis patients. METHODS The technique combines a novel clinical test with numerical optimization of a finite element model of the patient's spine. RESULTS A pilot study conducted on five patients showed that the model was able to provide accurate 3D reconstruction of the spine's midline and predict the spine's stiffness for each patient in flexion, bending, and rotation. Statistically significant variation of spinal stiffness was observed between the patients. CONCLUSION This result confirms that spinal biomechanics is patient-specific, which should be taken into consideration to individualize surgical treatment.

Hand-held 3D light field photography and applications

We propose a method to acquire 3D light fields using a hand-held camera, and describe several computational photography applications facilitated by our approach. As our input we take an image sequence from a camera translating along an approximately linear path with limited camera rotations. Users can acquire such data easily in a few seconds by moving a hand-held camera. We include a novel approach to resample the input into regularly sampled 3D light fields by aligning them in the spatio-temporal domain, and a technique for high-quality disparity estimation from light fields. We show applications including digital refocusing and synthetic aperture blur, foreground removal, selective colorization, and others.

Automatic Segmentation of the Eye in 3D Magnetic Resonance Imaging: A novel Statistical Shape Model for treatment planning of Retinoblastoma

Purpose: Proper delineation of ocular anatomy in 3D imaging is a big challenge, particularly when developing treatment plans for ocular diseases. Magnetic Resonance Imaging (MRI) is nowadays utilized in clinical practice for the diagnosis confirmation and treatment planning of retinoblastoma in infants, where it serves as a source of information, complementary to the Fundus or Ultrasound imaging. Here we present a framework to fully automatically segment the eye anatomy in the MRI based on 3D Active Shape Models (ASM), we validate the results and present a proof of concept to automatically segment pathological eyes. Material and Methods: Manual and automatic segmentation were performed on 24 images of healthy children eyes (3.29±2.15 years). Imaging was performed using a 3T MRI scanner. The ASM comprises the lens, the vitreous humor, the sclera and the cornea. The model was fitted by first automatically detecting the position of the eye center, the lens and the optic nerve, then aligning the model and fitting it to the patient. We validated our segmentation method using a leave-one-out cross validation. The segmentation results were evaluated by measuring the overlap using the Dice Similarity Coefficient (DSC) and the mean distance error. Results: We obtained a DSC of 94.90±2.12% for the sclera and the cornea, 94.72±1.89% for the vitreous humor and 85.16±4.91% for the lens. The mean distance error was 0.26±0.09mm. The entire process took 14s on average per eye. Conclusion: We provide a reliable and accurate tool that enables clinicians to automatically segment the sclera, the cornea, the vitreous humor and the lens using MRI. We additionally present a proof of concept for fully automatically segmenting pathological eyes. This tool reduces the time needed for eye shape delineation and thus can help clinicians when planning eye treatment and confirming the extent of the tumor.

3D Intervertebral Disc Localization and Segmentation from MR Images by Data-Driven Regression and Classification

In this paper we propose a new fully-automatic method for localizing and segmenting 3D intervertebral discs from MR images, where the two problems are solved in a unified data-driven regression and classification framework. We estimate the output (image displacements for localization, or fg/bg labels for segmentation) of image points by exploiting both training data and geometric constraints simultaneously. The problem is formulated in a unified objective function which is then solved globally and efficiently. We validate our method on MR images of 25 patients. Taking manually labeled data as the ground truth, our method achieves a mean localization error of 1.3 mm, a mean Dice metric of 87%, and a mean surface distance of 1.3 mm. Our method can be applied to other localization and segmentation tasks.

Localization and Segmentation of 3D Intervertebral Discs in MR Images by Data Driven Estimation

This paper addresses the problem of fully-automatic localization and segmentation of 3D intervertebral discs (IVDs) from MR images. Our method contains two steps, where we first localize the center of each IVD, and then segment IVDs by classifying image pixels around each disc center as foreground (disc) or background. The disc localization is done by estimating the image displacements from a set of randomly sampled 3D image patches to the disc center. The image displacements are estimated by jointly optimizing the training and test displacement values in a data-driven way, where we take into consideration both the training data and the geometric constraint on the test image. After the disc centers are localized, we segment the discs by classifying image pixels around disc centers as background or foreground. The classification is done in a similar data-driven approach as we used for localization, but in this segmentation case we are aiming to estimate the foreground/background probability of each pixel instead of the image displacements. In addition, an extra neighborhood smooth constraint is introduced to enforce the local smoothness of the label field. Our method is validated on 3D T2-weighted turbo spin echo MR images of 35 patients from two different studies. Experiments show that compared to state of the art, our method achieves better or comparable results. Specifically, we achieve for localization a mean error of 1.6-2.0 mm, and for segmentation a mean Dice metric of 85%-88% and a mean surface distance of 1.3-1.4 mm.

Rapid method to express and purify human membrane protein using the Xenopus oocyte system for functional and low-resolution structural analysis.

Progress toward elucidating the 3D structures of eukaryotic membrane proteins has been hampered by the lack of appropriate expression systems. Recent work using the Xenopus oocyte as a novel expression system for structural analysis demonstrates the capability of providing not only the significant amount of protein yields required for structural work but also the expression of eukaryotic membrane proteins in a more native and functional conformation. There is a long history using the oocyte expression system as an efficient tool for membrane transporter and channel expression in direct functional analysis, but improvements in robotic injection systems and protein yield optimization allow the rapid scalability of expressed proteins to be purified and characterized in physiologically relevant structural states. Traditional overexpression systems (yeast, bacteria, and insect cells) by comparison require chaotropic conditions over several steps for extraction, solubilization, and purification. By contrast, overexpressing within the oocyte system for subsequent negative-staining transmission electron microscopy studies provides a single system that can functionally assess and purify eukaryotic membrane proteins in fewer steps maintaining the physiological properties of the membrane protein.

Can 3D ultrasound identify trochlea dysplasia in newborns? Evaluation and applicability of a technique.

Femoro-patellar dysplasia is considered as a significant risk factor of patellar instability. Different studies suggest that the shape of the trochlea is already developed in early childhood. Therefore early identification of a dysplastic configuration might be relevant information for the treating physician. An easy applicable routine screening of the trochlea is yet not available. The purpose of this study was to establish and evaluate a screening method for femoro-patellar dysplasia using 3D ultrasound. From 2012 to 2013 we prospectively imaged 160 consecutive femoro-patellar joints in 80 newborns from the 36th to 61st gestational week that underwent a routine hip sonography (Graf). All ultrasounds were performed by a pediatric radiologist with only minimal additional time to the routine hip ultrasound. In 30° flexion of the knee, axial, coronal, and sagittal reformats were used to standardize a reconstructed axial plane through the femoral condyle and the mid-patella. The sulcus angle, the lateral-to-medial facet ratio of the trochlea and the shape of the patella (Wiberg Classification) were evaluated. In all examinations reconstruction of the standardized axial plane was achieved, the mean trochlea angle was 149.1° (SD 4.9°), the lateral-to-medial facet ratio of the trochlea ratio was 1.3 (SD 0.22), and a Wiberg type I patella was found in 95% of the newborn. No statistical difference was detected between boys and girls. Using standardized reconstructions of the axial plane allows measurements to be made with lower operator dependency and higher accuracy in a short time. Therefore 3D ultrasound is an easy applicable and powerful tool to identify trochlea dysplasia in newborns and might be used for screening for trochlea dysplasia.

VIRTOPSY--scientific documentation, reconstruction and animation in forensic: individual and real 3D data based geo-metric approach including optical body/object surface and radiological CT/MRI scanning.

Until today, most of the documentation of forensic relevant medical findings is limited to traditional 2D photography, 2D conventional radiographs, sketches and verbal description. There are still some limitations of the classic documentation in forensic science especially if a 3D documentation is necessary. The goal of this paper is to demonstrate new 3D real data based geo-metric technology approaches. This paper present approaches to a 3D geo-metric documentation of injuries on the body surface and internal injuries in the living and deceased cases. Using modern imaging methods such as photogrammetry, optical surface and radiological CT/MRI scanning in combination it could be demonstrated that a real, full 3D data based individual documentation of the body surface and internal structures is possible in a non-invasive and non-destructive manner. Using the data merging/fusing and animation possibilities, it is possible to answer reconstructive questions of the dynamic development of patterned injuries (morphologic imprints) and to evaluate the possibility, that they are matchable or linkable to suspected injury-causing instruments. For the first time, to our knowledge, the method of optical and radiological 3D scanning was used to document the forensic relevant injuries of human body in combination with vehicle damages. By this complementary documentation approach, individual forensic real data based analysis and animation were possible linking body injuries to vehicle deformations or damages. These data allow conclusions to be drawn for automobile accident research, optimization of vehicle safety (pedestrian and passenger) and for further development of crash dummies. Real 3D data based documentation opens a new horizon for scientific reconstruction and animation by bringing added value and a real quality improvement in forensic science.

3D documentation and visualization of external injury findings by integration of simple photography in CT/MRI data sets (IprojeCT).

This study evaluated the feasibility of documenting patterned injury using three dimensions and true colour photography without complex 3D surface documentation methods. This method is based on a generated 3D surface model using radiologic slice images (CT) while the colour information is derived from photographs taken with commercially available cameras. The external patterned injuries were documented in 16 cases using digital photography as well as highly precise photogrammetry-supported 3D structured light scanning. The internal findings of these deceased were recorded using CT and MRI. For registration of the internal with the external data, two different types of radiographic markers were used and compared. The 3D surface model generated from CT slice images was linked with the photographs, and thereby digital true-colour 3D models of the patterned injuries could be created (Image projection onto CT/IprojeCT). In addition, these external models were merged with the models of the somatic interior. We demonstrated that 3D documentation and visualization of external injury findings by integration of digital photography in CT/MRI data sets is suitable for the 3D documentation of individual patterned injuries to a body. Nevertheless, this documentation method is not a substitution for photogrammetry and surface scanning, especially when the entire bodily surface is to be recorded in three dimensions including all external findings, and when precise data is required for comparing highly detailed injury features with the injury-inflicting tool.

Non-Contact Documentation of Physical Characteristics of Ecstasy Tablets, Hemp Coins, and Imprint Punches by using 3D Optical Surface Scanning

The description of seized illicit ecstasy tablets and other pressed drug products is an important step in casework. The physical and visual analysis and the description of the characteristics can be employed for intelligence purposes. Besides photography and manual measurements of dimensions, some optical instruments are employed for detailed measurements of physical characteristics. In this work, the method of 3D surface digitizing is introduced as a suitable tool for highly accurate documentation of small objects, especially for pressed drug products. The resulting detailed information about the geometry, and the results of an automatic comparison of apparently uniform tablets and coins with punches, can support drug intelligence.

Comparison of 3D kinetic and hydrodynamic models to ROSINA-COPS measurements of the neutral coma of 67P/Churyumov-Gerasimenko

67P/Churyumov-Gerasimenko (67P) is a Jupiter-family comet and the object of investigation of the European Space Agency mission Rosetta. This report presents the first full 3D simulation results of 67P’s neutral gas coma. In this study we include results from a direct simulation Monte Carlo method, a hydrodynamic code, and a purely geometric calculation which computes the total illuminated surface area on the nucleus. All models include the triangulated 3D shape model of 67P as well as realistic illumination and shadowing conditions. The basic concept is the assumption that these illumination conditions on the nucleus are the main driver for the gas activity of the comet. As a consequence, the total production rate of 67P varies as a function of solar insolation. The best agreement between the model and the data is achieved when gas fluxes on the night side are in the range of 7% to 10% of the maximum flux, accounting for contributions from the most volatile components. To validate the output of our numerical simulations we compare the results of all three models to in situ gas number density measurements from the ROSINA COPS instrument. We are able to reproduce the overall features of these local neutral number density measurements of ROSINA COPS for the time period between early August 2014 and January 1 2015 with all three models. Some details in the measurements are not reproduced and warrant further investigation and refinement of the models. However, the overall assumption that illumination conditions on the nucleus are at least an important driver of the gas activity is validated by the models. According to our simulation results we find the total production rate of 67P to be constant between August and November 2014 with a value of about 1 × 10²⁶ molecules s⁻¹.

Comparison of 2.5D and 3D Quantification of Femoral Head Coverage in Normal Control Subjects and Patients with Hip Dysplasia.

Hip dysplasia is characterized by insufficient femoral head coverage (FHC). Quantification of FHC is of importance as the underlying goal of the surgery to treat hip dysplasia is to restore a normal acetabular morphology and thereby to improve FHC. Unlike a pure 2D X-ray radiograph-based measurement method or a pure 3D CT-based measurement method, previously we presented a 2.5D method to quantify FHC from a single anteriorposterior (AP) pelvic radiograph. In this study, we first quantified and compared 3D FHC between a normal control group and a patient group using a CT-based measurement method. Taking the CT-based 3D measurements of FHC as the gold standard, we further quantified the bias, precision and correlation between the 2.5D measurements and the 3D measurements on both the control group and the patient group. Based on digitally reconstructed radiographs (DRRs), we investigated the influence of the pelvic tilt on the 2.5D measurements of FHC. The intraclass correlation coefficients (ICCs) for absolute agreement was used to quantify interobserver reliability and intraobserver reproducibility of the 2.5D measurement technique. The Pearson correlation coefficient, r, was used to determine the strength of the linear association between the 2.5D and the 3D measurements. Student's t-test was used to determine whether the differences between different measurements were statistically significant. Our experimental results demonstrated that both the interobserver reliability and the intraobserver reproducibility of the 2.5D measurement technique were very good (ICCs > 0.8). Regression analysis indicated that the correlation was very strong between the 2.5D and the 3D measurements (r = 0.89, p < 0.001). Student's t-test showed that there were no statistically significant differences between the 2.5D and the 3D measurements of FHC on the patient group (p > 0.05). The results of this study provided convincing evidence demonstrating the validity of the 2.5D measurements of FHC from a single AP pelvic radiograph and proved that it could serve as a surrogate for 3D CT-based measurements. Thus it may be possible to use this method to avoid a CT scan for the purpose of estimating 3D FHC in diagnosis and post-operative treatment evaluation of patients with hip dysplasia.

Engineering an in vitro air-blood barrier by 3D bioprinting

Intensive efforts in recent years to develop and commercialize in vitro alternatives in the field of risk assessment have yielded new promising two- and three dimensional (3D) cell culture models. Nevertheless, a realistic 3D in vitro alveolar model is not available yet. Here we report on the biofabrication of the human air-blood tissue barrier analogue composed of an endothelial cell, basement membrane and epithelial cell layer by using a bioprinting technology. In contrary to the manual method, we demonstrate that this technique enables automatized and reproducible creation of thinner and more homogeneous cell layers, which is required for an optimal air-blood tissue barrier. This bioprinting platform will offer an excellent tool to engineer an advanced 3D lung model for high-throughput screening for safety assessment and drug efficacy testing.

Deep Points Consolidation

In this paper, we present a consolidation method that is based on a new representation of 3D point sets. The key idea is to augment each surface point into a deep point by associating it with an inner point that resides on the meso-skeleton, which consists of a mixture of skeletal curves and sheets. The deep points representation is a result of a joint optimization applied to both ends of the deep points. The optimization objective is to fairly distribute the end points across the surface and the meso-skeleton, such that the deep point orientations agree with the surface normals. The optimization converges where the inner points form a coherent meso-skeleton, and the surface points are consolidated with the missing regions completed. The strength of this new representation stems from the fact that it is comprised of both local and non-local geometric information. We demonstrate the advantages of the deep points consolidation technique by employing it to consolidate and complete noisy point-sampled geometry with large missing parts.