A computational framework for 3D mechanical modeling of plant morphogenesis with cellular resolution.

The link between genetic regulation and the definition of form and size during morphogenesis remains largely an open question in both plant and animal biology. This is partially due to the complexity of the process, involving extensive molecular networks, multiple feedbacks between different scales of organization and physical forces operating at multiple levels. Here we present a conceptual and modeling framework aimed at generating an integrated understanding of morphogenesis in plants. This framework is based on the biophysical properties of plant cells, which are under high internal turgor pressure, and are prevented from bursting because of the presence of a rigid cell wall. To control cell growth, the underlying molecular networks must interfere locally with the elastic and/or plastic extensibility of this cell wall. We present a model in the form of a three dimensional (3D) virtual tissue, where growth depends on the local modulation of wall mechanical properties and turgor pressure. The model shows how forces generated by turgor-pressure can act both cell autonomously and non-cell autonomously to drive growth in different directions. We use simulations to explore lateral organ formation at the shoot apical meristem. Although different scenarios lead to similar shape changes, they are not equivalent and lead to different, testable predictions regarding the mechanical and geometrical properties of the growing lateral organs. Using flower development as an example, we further show how a limited number of gene activities can explain the complex shape changes that accompany organ outgrowth.

Three-dimensional study of the skin/subcutaneous complex using in vivo whole body 3T MRI: review of the literature and confirmation of a generic pattern of organization.

PURPOSE: With a view to developing a tool for predicting the behavior of soft tissues during plastic surgery procedures, we looked for the existence of homologies in the overall pattern of organization of the skin/subcutaneous tissue complex between various body parts, using high-resolution in vivo imaging methods and data available in the literature. METHODS: 3T MRI scanning sequences were performed using appropriate radiofrequency coils on the face, thorax, breast, abdomen and lower extremity of six healthy volunteers. The radiological findings were segmented and converted into volumetric data. RESULTS: The superficial and deep adipose tissue was found to be clearly separated by an intermediate layer called stratum membranosum or superficial fascia. This continuous layer covered all the anatomical parts of the body examined. It was found to have several components in the trunk and limbs and to form a continuous layer with the superficial muscular aponeurotic system in the face. A retaining connective network consisting of superficial and deep retinacula cutis detected in all the regions investigated sometimes formed more densely packed structures playing the role of skin ligaments. CONCLUSION: The results of a 3T MRI study on subcutaneous tissue showed the existence of a common pattern of organization of the skin-subcutaneous tissue complex in the various parts of the body studied. This general model is subject to quantitative variations and tissue differentiation processes promoting the sliding or contractility of the supporting tissue. Three-dimensional reconstructions were obtained by post-processing the MRI images and will be used to perform pre-surgical simulations by settings a generic model that can be adapted to the different localization of the human body in a procedural way.

A rigged model of the breast for preoperative surgical planning.

In breast surgical practice, drawing is part of the preoperative planning procedure and is essential for a successful operation. In this study, we design a pipeline to assist surgeons with patient-specific breast surgical drawings. We use a deformable torso model containing the surgical patterns to match any breast surface scan. To be compatible with surgical timing, we build an articulated model through a skinning process coupled with shape deformers to enhance a fast registration process. On one hand, the scalable bones of the skinning account for pose and morphological variations of the patients. On the other hand, pre-designed artistic blendshapes create a linear space for guaranteeing anatomical variations. Then, we apply meaningful constraints to the model to find a trade-off between precision and speed. The experiments were conducted on 7 patients, in 2 different poses (prone and supine) with a breast size ranging from 36A and 42C (US/UK bra sizing). The acquisitions were obtained using the depth camera Structure Sensor, and the breast scans were acquired in less than 1 minute. The result is a registration method converging within a few seconds (3 maximum), reaching a Mean Absolute Error of 2.3 mm for mesh registration and 8.0 mm for breast anatomical landmarks. Compared to the existing literature, our model can be personalized and does not require any database. Finally, our registered model can be used to transfer surgical reference patterns onto any patient in any position.

Quantitative Magnetic Resonance Imaging Assessment of the Quadriceps Changes during an Extreme Mountain Ultramarathon.

INTRODUCTION/PURPOSE: Extreme ultra-endurance races are growing in popularity, but their effects on skeletal muscles remain mostly unexplored. This longitudinal study explores physiological changes in mountain ultramarathon athletes' quadriceps using quantitative magnetic resonance imaging (MRI) coupled with serological biomarkers. The study aimed to monitor the longitudinal effect of the race and recovery and to identify local inflammatory and metabolic muscle responses by codetection of biological markers. METHODS: An automatic image processing framework was designed to extract imaging-based biomarkers from quantitative MRI acquisitions of the upper legs of 20 finishers at three time points. The longitudinal effect of the race was demonstrated by analyzing the image markers with dedicated biostatistical analysis. RESULTS: Our framework allows for a reliable calculation of statistical data not only inside the whole quadriceps volume but also within each individual muscle head. Local changes in MRI parameters extracted from quantitative maps were described and found to be significantly correlated with principal serological biomarkers of interest. A decrease in the PDFF after the race and a stable paramagnetic susceptibility value were found. Pairwise post hoc tests suggested that the recovery process differs among the muscle heads. CONCLUSIONS: This longitudinal study conducted during a prolonged and extreme mechanical stress showed that quantitative MRI-based markers of inflammation and metabolic response can detect local changes related to the prolonged exercise, with differentiated involvement of each head of the quadriceps muscle as expected in such eccentric load. Consistent and efficient extraction of the local biomarkers enables to highlight the interplay/interactions between blood and MRI biomarkers. This work indeed proposes an automatized analytic framework to tackle the time-consuming and mentally exhausting segmentation task of muscle heads in large multi-time-point cohorts.

Medial axis segmentation of cranial nerves using shape statistics-aware discrete deformable models.

PURPOSE: We propose a segmentation methodology for brainstem cranial nerves using statistical shape model (SSM)-based deformable 3D contours from T2 MR images. METHODS: We create shape models for ten pairs of cranial nerves. High-resolution T2 MR images are segmented for nerve centerline using a 1-Simplex discrete deformable 3D contour model. These segmented centerlines comprise training datasets for the shape model. Point correspondence for the training dataset is performed using an entropy-based energy minimization framework applied to particles located on the centerline curve. The shape information is incorporated into the 1-Simplex model by introducing a shape-based internal force, making the deformation stable against low resolution and image artifacts. RESULTS: The proposed method is validated through extensive experiments using both synthetic and patient MRI data. The robustness and stability of the proposed method are experimented using synthetic datasets. SSMs are constructed independently for ten pairs (CNIII-CNXII) of brainstem cranial nerves using ten non-pathological image datasets of the brainstem. The constructed ten SSMs are assessed in terms of compactness, specificity and generality. In order to quantify the error distances between segmented results and ground truths, two metrics are used: mean absolute shape distance (MASD) and Hausdorff distance (HD). MASD error using the proposed shape model is 0.19 ± 0.13 (mean ± std. deviation) mm and HD is 0.21 mm which are sub-voxel accuracy given the input image resolution. CONCLUSION: This paper described a probabilistic digital atlas of the ten brainstem-attached cranial nerve pairs by incorporating a statistical shape model with the 1-Simplex deformable contour. The integration of shape information as a priori knowledge results in robust and accurate centerline segmentations from even low-resolution MRI data, which is essential in neurosurgical planning and simulations for accurate and robust 3D patient-specific models of critical tissues including cranial nerves.

Mutant Best1 Expression and Impaired Phagocytosis in an iPSC Model of Autosomal Recessive Bestrophinopathy.

Autosomal recessive bestrophinopathy (ARB) is caused by mutations in the gene BEST1 which encodes bestrophin 1 (Best1), an anion channel expressed in retinal pigment epithelial (RPE) cells. It has been hypothesized that ARB represents the human null phenotype for BEST1 and that this occurs due to nonsense mediated decay (NMD). To test this hypothesis, we generated induced pluripotent stem cells (iPSCs) from a patient with ARB and her parents. After differentiation to retinal pigment epithelial (iPSC-RPE) cells, both BEST1 mRNA and Best1 protein expression were compared to controls. BEST1 mRNA expression levels, determined by quantitative PCR, were similar in ARB iPSC-RPE, parental cells, and genetically unrelated controls. Western blotting revealed that CRALBP and RPE65 were expressed within the range delineated by unrelated controls in iPSC-RPE from the ARB donor and her parents. Best1 protein was detected in different clones of ARB iPSC-RPE, but at reduced levels compared to all controls. When tested for the ability to phagocytose photoreceptor outer segments, ARB iPSC-RPE exhibited impaired internalization. These data suggest that impaired phagocytosis is a trait common to the bestrophinopathies. Furthermore, ARB is not universally the result of NMD and ARB, in this patient, is not due to the absence of Best1.

Self-righting potential and the evolution of shell shape in Galápagos tortoises.

Self-righting, the capacity of an animal to self-turn after falling on its back, is a fitness-related trait. Delayed self-righting can result in loss of mating opportunities or death. Traits involved in self-righting may therefore be under selection. Galápagos giant tortoises have two main shell morphologies - saddleback and domed - that have been proposed to be adaptive. The more sloped shape on the sides of the shell and the longer extension of neck and legs of the saddlebacks could have evolved to optimize self-righting. The drier environments with more uneven surfaces where the saddleback tortoises occur increases their risk to fall on their back while walking. The ability to fast overturn could reduce the danger of dying. To test this hypothesis, we used 3D shell reconstructions of 89 Galápagos giant tortoises from three domed and two saddleback species to compare self-righting potential of the two shell morphotypes. Our results indicate that saddleback shells require higher energy input to self-right than domed ones. This suggests that several traits associated with the saddleback shell morphology could have evolved to facilitate self-righting. Studying the functional performances of fitness-related traits, as in this work, could provide important insight into the adaptive value of traits.

MRI-Based Medial Axis Extraction and Boundary Segmentation of Cranial Nerves Through Discrete Deformable 3D Contour and Surface Models.

This paper presents a segmentation technique to identify the medial axis and the boundary of cranial nerves. We utilize a 3-D deformable one-simplex discrete contour model to extract the medial axis of each cranial nerve. This contour model represents a collection of two-connected vertices linked by edges, where vertex position is determined by a Newtonian expression for vertex kinematics featuring internal and external forces, the latter of which include attractive forces toward the nerve medial axis. We exploit multiscale vesselness filtering and minimal path techniques in the medial axis extraction method, which also computes a radius estimate along the path. Once we have the medial axis and the radius function of a nerve, we identify the nerve surface using a two-simplex deformable model, which expands radially and can accommodate any nerve shape. As a result, the method proposed here combines the benefits of explicit contour and surface models, while also achieving a cornerstone for future work that will emphasize shape statistics, static collision with other critical structures, and tree-shape analysis.

Geometric and mechanical evaluation of 3D-printing materials for skull base anatomical education and endoscopic surgery simulation - A first step to create reliable customized simulators.

INTRODUCTION: Endoscopic skull base surgery allows minimal invasive therapy through the nostrils to treat infectious or tumorous diseases. Surgical and anatomical education in this field is limited by the lack of validated training models in terms of geometric and mechanical accuracy. We choose to evaluate several consumer-grade materials to create a patient-specific 3D-printed skull base model for anatomical learning and surgical training. METHODS: Four 3D-printed consumer-grade materials were compared to human cadaver bone: calcium sulfate hemihydrate (named Multicolor), polyamide, resin and polycarbonate. We compared the geometric accuracy, forces required to break thin walls of materials and forces required during drilling. RESULTS: All materials had an acceptable global geometric accuracy (from 0.083mm to 0.203mm of global error). Local accuracy was better in polycarbonate (0.09mm) and polyamide (0.15mm) than in Multicolor (0.90mm) and resin (0.86mm). Resin and polyamide thin walls were not broken at 200N. Forces needed to break Multicolor thin walls were 1.6-3.5 times higher than in bone. For polycarbonate, forces applied were 1.6-2.5 times higher. Polycarbonate had a mode of fracture similar to the cadaver bone. Forces applied on materials during drilling followed a normal distribution except for the polyamide which was melted. Energy spent during drilling was respectively 1.6 and 2.6 times higher on bone than on PC and Multicolor. CONCLUSION: Polycarbonate is a good substitute of human cadaver bone for skull base surgery simulation. Thanks to short lead times and reasonable production costs, patient-specific 3D printed models can be used in clinical practice for pre-operative training, improving patient safety.

Bone motion analysis from dynamic MRI: acquisition and tracking.

RATIONALE AND OBJECTIVES: For diagnosis, preoperative planning and postoperative guides, an accurate estimate of joint kinematics is required. It is important to acquire joint motion actively with real-time protocols. MATERIALS AND METHODS: We bring together MRI developments and new image processing methods in order to automatically extract active bone kinematics from multi-slice real-time dynamic MRI. We introduce a tracking algorithm based on 2D/3D registration and a procedure to validate the technique by using both dynamic and sequential MRI, providing a gold standard bone position measurement. RESULTS: We present our technique for optimizing jointly the tracking method and the acquisition protocol to overcome the trade-off in acquisition time and tracking accuracy. As a case study, we apply this methodology on a human hip joint. CONCLUSION: The final protocol (bFFE, TR/TE 3.5/1.1 ms, Flip angle 80 degrees , pixel size 4.7 x 2.6 mm, partial Fourier reduction factor of 0.65 in read direction, SENSE acceleration factor of 2, frame rate = 6.7 frames/s) provides sufficient morphological data for bone tracking to be carried out with an accuracy of 3 degrees in terms of joint angle.

Control of Maintenance and Regeneration of Planarian Eyes by ovo.

PURPOSE: Following decapitation, the planarian Schmidtea mediterranea regenerates its head and eyes. The gene ovo is required for eye maintenance and regeneration in response to wounding. In this study, we investigated whether eye regeneration in S. mediterranea could occur absent a wound healing response. METHODS: One hundred twenty S. mediterranea were treated with ovo RNA interference (RNAi) or control (unc-22) RNAi by feeding double-stranded RNA (dsRNA). Following eye loss, ovo RNAi treatment was halted and replaced with control RNAi treatment. Quantitative real-time PCR (qPCR) was used to monitor ovo expression. Eye functionality was monitored via a phototaxis assay. Photoreceptor neurons were visualized via immunofluorescence staining of arrestin. RESULTS: Treatment with ovo RNAi caused eyes to gradually shrink until they were completely absent. One hundred percent of ovo RNAi-treated planarians lost both eyes within 137 days of treatment onset. ovo RNAi-treated planarians were unable to regenerate eyes in response to decapitation. Upon removal of ovo RNAi, eyes became visible as small pigmented spots in the head within 28 days. The eyes slowly developed, appearing to gain pigmented cells first and then nonpigmented photoreceptors. Phototaxis assays demonstrated functional eye loss and eye restoration. ovo mRNA was significantly decreased following treatment with ovo RNAi and significantly increased following removal of ovo RNAi. Arrestin staining was present in the eyes, optic nerves, and optic chiasm of worms with regenerated eyes but not in eyeless worms. CONCLUSIONS: S. mediterranea have the ability to generate functional eyes in the absence of a wound healing response. This ability requires the expression of ovo.

Autosomal Recessive Bestrophinopathy Is Not Associated With the Loss of Bestrophin-1 Anion Channel Function in a Patient With a Novel BEST1 Mutation.

PURPOSE: Mutations in BEST1, encoding bestrophin-1 (Best1), cause autosomal recessive bestrophinopathy (ARB). Encoding bestrophin-1 is a pentameric anion channel localized to the basolateral plasma membrane of the RPE. Here, we characterize the effects of the mutations R141H (CGC > CAC) and I366fsX18 (c.1098_1100+7del), identified in a patient in our practice, on Best1 trafficking, oligomerization, and channel activity. METHODS: Currents of Cl- were assessed in transfected HEK293 cells using whole-cell patch clamp. Best1 localization was assessed by confocal microscopy in differentiated, human-induced pluripotent stem cell-derived RPE (iPSC-RPE) cells following expression of mutants via adenovirus-mediated gene transfer. Oligomerization was evaluated by coimmunoprecipitation in iPSC-RPE and MDCK cells. RESULTS: Compared to Best1, Best1 I366fsX18 currents were increased while Best1 R141H Cl- currents were diminished. Coexpression of Best1 R141H with Best1 or Best1 I366fsX18 resulted in rescued channel activity. Overexpressed Best1, Best1 R141H, and Best1 I366fsX18 were all properly localized in iPSC-RPE cells; Best1 R141H and Best1 I366fsX18 coimmunoprecipitated with endogenous Best1 in iPSC-RPE cells and with each other in MDCK cells. CONCLUSIONS: The first 366 amino acids of Best1 are sufficient to mediate channel activity and homo-oligomerization. The combination of Best1 and Best1 R141H does not cause disease, while Best1 R141H together with Best1 I366fsX18 causes ARB. Since both combinations generate comparable Cl- currents, this indicates that ARB in this patient is not caused by a loss of channel activity. Moreover, Best1 I366fsX18 differs from Best1 in that it lacks most of the cytosolic C-terminal domain, suggesting that the loss of this region contributes significantly to the pathogenesis of ARB in this patient.

Real-time muscle deformation via decoupled modeling of solid and muscle fiber mechanics.

This paper presents a novel approach for simulating 3D muscle deformations with complex architectures. The approach consists in choosing the best model formulation in terms of computation cost and accuracy, that mixes a volumetric-tissue model based on finite element method (3D FEM), a muscle fiber model (Hill contractile 1D element) and a membrane model accounting for aponeurosis tissue (2D FEM). The separate models are mechanically binded using barycentric embeddings. Our approach allows the computation of several fiber directions in one coarse finite element, and thus, strongly decreases the required finite element resolution to predict muscle deformation during contraction. Using surface registration, fibers tracks of specific architecture can be transferred from a template to subject morphology, and then simulated. As a case study, three different architectures are simulated and compared to their equivalent one dimensional Hill wire model simulations.

An auxin-mediated shift toward growth isotropy promotes organ formation at the shoot meristem in Arabidopsis.

To control morphogenesis, molecular regulatory networks have to interfere with the mechanical properties of the individual cells of developing organs and tissues, but how this is achieved is not well known. We study this issue here in the shoot meristem of higher plants, a group of undifferentiated cells where complex changes in growth rates and directions lead to the continuous formation of new organs. Here, we show that the plant hormone auxin plays an important role in this process via a dual, local effect on the extracellular matrix, the cell wall, which determines cell shape. Our study reveals that auxin not only causes a limited reduction in wall stiffness but also directly interferes with wall anisotropy via the regulation of cortical microtubule dynamics. We further show that to induce growth isotropy and organ outgrowth, auxin somehow interferes with the cortical microtubule-ordering activity of a network of proteins, including AUXIN BINDING PROTEIN 1 and KATANIN 1. Numerical simulations further indicate that the induced isotropy is sufficient to amplify the effects of the relatively minor changes in wall stiffness to promote organogenesis and the establishment of new growth axes in a robust manner.

Wastewater use in algae production for generation of renewable resources: a review and preliminary results.

Microalgae feedstock production can be integrated with wastewater and industrial sources of carbon dioxide. This study reviews the literature on algae grown on wastewater and includes a preliminary analysis of algal production based on anaerobic digestion sludge centrate from the Howard F. Curren Advanced Wastewater Treatment Plant (HFC AWTP) in Tampa, Florida and secondary effluent from the City of Lakeland wastewater treatment facilities in Lakeland, Florida. It was demonstrated that a mixed culture of wild algae species could successfully be grown on wastewater nutrients and potentially scaled to commercial production. Algae have demonstrated the ability to naturally colonize low-nutrient effluent water in a wetland treatment system utilized by the City of Lakeland. The results from these experiments show that the algae grown in high strength wastewater from the HFC AWTP are light-limited when cultivated indoor since more than 50% of the outdoor illumination is attenuated in the greenhouse.An analysis was performed to determine the mass of algae that can be supported by the wastewater nutrients (mainly nitrogen and phosphorous) available from the two Florida cities. The study was guided by the growth and productivity data obtained for algal growth in the photobioreactors in operation at the University of South Florida. In the analysis, nutrients and light are assumed to be limited, while CO2 is abundantly available. There is some limitation on land, especially since the HFC AWTP is located at the Port of Tampa. The temperature range in Tampa is assumed to be suitable for algal growth year round. Assuming that the numerous technical challenges to achieving commercial-scale algal production can be met, the results presented suggest that an excess of 71 metric tons per hectare per year of algal biomass can be produced. Two energy production options were considered; liquid biofuels from feedstock with high lipid content, and biogas generation from anaerobic digestion of algae biomass. The total potential oil volume was determined to be approximately 337,500 gallons per year, which may result in the annual production of 270,000 gallons of biodiesel when 80% conversion efficiency is assumed. This production level would be able to sustain approximately 450 cars per year on average. Potential biogas production was estimated to be above 415,000 kg/yr, the equivalent of powering close to 500 homes for a year.

3D volumetric muscle modeling for real-time deformation analysis with FEM.

Computer simulation is promising numerical tool to study muscle volumetric deformations. However, most models are facing very long computation time and thus are based on simplified wire Hill muscle model. The purpose of this study is to develop a real-time three-dimensional biomechanical model of volumetric muscle based on modified Hill model for the active stress which is controlled from EMG recordings. Finite element model is used to estimate the passive behavior of the muscle and tendons during contraction. We demonstrate that this 3D model implementation is very cost effective with respect to the computation time and the simulation gives good results compared to real measured data. Thus, this effective implementation will allow implementing much more complex and realistic models considering the muscle as volumetric continuum, with moderate computation time.

Extracting skeletal muscle fiber fields from noisy diffusion tensor data.

Diffusion Tensor Imaging (DTI) allows the non-invasive study of muscle fiber architecture but musculoskeletal DTI suffers from low signal-to-noise ratio. Noise in the computed tensor fields can lead to poorly reconstructed muscle fiber fields. This paper describes an algorithm for producing denoised muscle fiber fields from noisy diffusion tensor data as well as its preliminary validation. The algorithm computes a denoised vector field by finding the components of its Helmholtz-Hodge decomposition that optimally match the diffusion tensor field. A key feature of the algorithm is that it performs denoising of the vector field simultaneously with its extraction from the noisy tensor field. This allows the vector field reconstruction to be constrained by the architectural properties of skeletal muscles. When compared to primary eigenvector fields extracted from noisy synthetic data, the denoised vector fields show greater similarity to the ground truth for signal-to-noise ratios ranging from 20 to 5. Similarity greater than 0.9 (in terms of fiber direction) is observed for all signal-to-noise ratios, for smoothing parameter values greater than or equal to 10 (larger values yield more smoothing). Fiber architectures were computed from human forearm diffusion tensor data using extracted primary eigenvectors and the denoised data. Qualitative comparison of the fiber fields showed that the denoised fields were anatomically more plausible than the noisy fields. From the results of experiments using both synthetic and real MR datasets we conclude that the denoising algorithm produces anatomically plausible fiber architectures from diffusion tensor images with a wide range of signal-to-noise ratios.

Musculoskeletal MRI segmentation using multi-resolution simplex meshes with medial representations.

The automatic segmentation of the musculoskeletal system from medical images is a particularly challenging task, due to its morphological complexity, its large variability in the population and its potentially large deformations. In this paper we propose a novel approach for musculoskeletal segmentation and registration based on simplex meshes. Such discrete models have already proven to be efficient and versatile for medical image segmentation. We extend the current framework by introducing a multi-resolution approach and a reversible medial representation, in order to reduce the complexity of geometric and non-penetration constraints computation. Our framework allows both inter and intra-patient registration (involving both rigid and elastic matching). We also show that the introduced representations facilitate morphological analysis. As a case study, we demonstrate that muscles, bones, ligaments and cartilages of the hip and the thigh can be registered at an interactive frame rate, in a time-efficient way (<30min), with a satisfactory accuracy ( approximately 1.5mm), and with a minimal amount of manual tasks.

MRI-based assessment of hip joint translations.

To better understand movement limitations and, to some extent, the pathogenesis of osteoarthritis, it is important to quantitatively measure femoroacetabular translations to assess if any joint subluxation occurs. In this paper, we aim at measuring hip joint displacements from magnetic resonance images (MRI) based on a surface registration technique. Because this measurement is related to the location of the hip joint center (HJC), we investigate and compare different HJC estimation approaches based on patient-specific 3D bone models. We estimate the HJC based on a simulated circumduction while minimizing inter-articular distance changes. Measurements of femoroacetabular translations during low amplitude abductions (80 samples) and extreme flexions (60 samples) in female professional dancers, which is a population potentially exposed to femoroacetabular impingements, do not show any significant subluxation.