The correlation of pore morphology, interconnectivity and physical properties of 3D ceramic scaffolds with bone ingrowth

In the design of tissue engineering scaffolds, design parameters including pore size, shape and interconnectivity, mechanical properties and transport properties should be optimized to maximize successful inducement of bone ingrowth. In this paper we describe a 3D micro-CT and pore partitioning study to derive pore scale parameters including pore radius distribution, accessible radius, throat radius, and connectivity over the pore space of the tissue engineered constructs. These pore scale descriptors are correlated to bone ingrowth into the scaffolds. Quantitative and visual comparisons show a strong correlation between the local accessible pore radius and bone ingrowth; for well connected samples a cutoff accessible pore radius of approximately 100 microM is observed for ingrowth. The elastic properties of different types of scaffolds are simulated and can be described by standard cellular solids theory: (E/E(0))=(rho/rho(s))(n). Hydraulic conductance and diffusive properties are calculated; results are consistent with the concept of a threshold conductance for bone ingrowth. Simple simulations of local flow velocity and local shear stress show no correlation to in vivo bone ingrowth patterns. These results demonstrate a potential for 3D imaging and analysis to define relevant pore scale morphological and physical properties within scaffolds and to provide evidence for correlations between pore scale descriptors, physical properties and bone ingrowth.

Measuring Visual Consistency in 3D Rendering Systems

One of the major challenges facing a present day game development company is the removal of bugs from such complex virtual environments. This work presents an approach for measuring the correctness of synthetic scenes generated by a rendering system of a 3D application, such as a computer game. Our approach builds a database of labelled point clouds representing the spatiotemporal colour distribution for the objects present in a sequence of bug-free frames. This is done by converting the position that the pixels take over time into the 3D equivalent points with associated colours. Once the space of labelled points is built, each new image produced from the same game by any rendering system can be analysed by measuring its visual inconsistency in terms of distance from the database. Objects within the scene can be relocated (manually or by the application engine); yet the algorithm is able to perform the image analysis in terms of the 3D structure and colour distribution of samples on the surface of the object. We applied our framework to the publicly available game RacingGame developed for Microsoft(R) Xna(R). Preliminary results show how this approach can be used to detect a variety of visual artifacts generated by the rendering system in a professional quality game engine.

3D anthropometry : from the ergonomist's perspective

Since the availability of 3D full body scanners and the associated software systems for operations with large point clouds, 3D anthropometry has been marketed as a breakthrough and milestone in ergonomic design. The assumptions made by the representatives of the 3D paradigm need to be critically reviewed though. 3D anthropometry has advantages as well as shortfalls, which need to be carefully considered. While it is apparent that the measurement of a full body point cloud allows for easier storage of raw data and improves quality control, the difficulties in calculation of standardized measurements from the point cloud are widely underestimated. Early studies that made use of 3D point clouds to derive anthropometric dimensions have shown unacceptable deviations from the standardized results measured manually. While 3D human point clouds provide a valuable tool to replicate specific single persons for further virtual studies, or personalize garment, their use in ergonomic design must be critically assessed. Ergonomic, volumetric problems are defined by their 2-dimensional boundary or one dimensional sections. A 1D/2D approach is therefore sufficient to solve an ergonomic design problem. As a consequence, all modern 3D human manikins are defined by the underlying anthropometric girths (2D) and lengths/widths (1D), which can be measured efficiently using manual techniques. Traditionally, Ergonomists have taken a statistical approach to design for generalized percentiles of the population rather than for a single user. The underlying method is based on the distribution function of meaningful single and two-dimensional anthropometric variables. Compared to these variables, the distribution of human volume has no ergonomic relevance. On the other hand, if volume is to be seen as a two-dimensional integral or distribution function of length and girth, the calculation of combined percentiles – a common ergonomic requirement - is undefined. Consequently, we suggest to critically review the cost and use of 3D anthropometry. We also recommend making proper use of widely available single and 2-dimensional anthropometric data in ergonomic design.

Lost in translation (and rotation) : rapid extrinsic calibration for 2D and 3D LIDARs

This paper describes a novel method for determining the extrinsic calibration parameters between 2D and 3D LIDAR sensors with respect to a vehicle base frame. To recover the calibration parameters we attempt to optimize the quality of a 3D point cloud produced by the vehicle as it traverses an unknown, unmodified environment. The point cloud quality metric is derived from Rényi Quadratic Entropy and quantifies the compactness of the point distribution using only a single tuning parameter. We also present a fast approximate method to reduce the computational requirements of the entropy evaluation, allowing unsupervised calibration in vast environments with millions of points. The algorithm is analyzed using real world data gathered in many locations, showing robust calibration performance and substantial speed improvements from the approximations.

Assessment of flood-related recharge to alluvial aquifers of an irrigated catchment following extended drought conditions using 3D visualisation and environmental tracers, Lockyer Valley, southeast Queensland, Australia.

The Lockyer Valley in southeast Queensland, Australia, hosts an economically significant alluvial aquifer system which has been impacted by prolonged drought conditions (~1997 to ~ 2009). Throughout this time, the system was under continued groundwater extraction, resulting in severe aquifer depletion. By 2008, much of the aquifer was at <30% of storage but some relief occurred with rains in early 2009. However, between December 2010 and January 2011, most of southeast Queensland experienced unprecedented flooding, which generated significant aquifer recharge. In order to understand the spatial and temporal controls of groundwater recharge in the alluvium, a detailed 3D lithological property model of gravels, sands and clays was developed using GOCAD software. The spatial distribution of recharge throughout the catchment was assessed using hydrograph data from about 400 groundwater observation wells screened at the base of the alluvium. Water levels from these bores were integrated into a catchment-wide 3D geological model using the 3D geological modelling software GOCAD; the model highlights the complexity of recharge mechanisms. To support this analysis, groundwater tracers (e.g. major and minor ions, stable isotopes, 3H and 14C) were used as independent verification. The use of these complementary methods has allowed the identification of zones where alluvial recharge primarily occurs from stream water during episodic flood events. However, the study also demonstrates that in some sections of the alluvium, rainfall recharge and discharge from the underlying basement into the alluvium are the primary recharge mechanisms of the alluvium. This is indicated by the absence of any response to the flood, as well as the observed old radiocarbon ages and distinct basement water chemistry signatures at these locations. Within the 3D geological model, integration of water chemistry and time-series displays of water level surfaces before and after the flood suggests that the spatial variations of the flood response in the alluvium are primarily controlled by the valley morphology and lithological variations within the alluvium. The integration of time-series of groundwater level surfaces in the 3D geological model also enables the quantification of the volumetric change of groundwater stored in the unconfined sections of this alluvial aquifer during drought and following flood events. The 3D representation and analysis of hydraulic and recharge information has considerable advantages over the traditional 2D approach. For example, while many studies focus on singular aspects of catchment dynamics and groundwater-surface water interactions, the 3D approach is capable of integrating multiple types of information (topography, geological, hydraulic, water chemistry and spatial) into a single representation which provides valuable insights into the major factors controlling aquifer processes.

Review of 3D model development with application to groundwater studies in New Zealand 1996 – 2011

Three dimensional geological modelling techniques have been applied since 1996 with an aim to characterise the lithological and chronological units of New Zealand’s many diverse aquifers. Models of property-scattered data have also been applied to assess physical properties of aquifers and the distribution of groundwater chemistry, including groundwater age, to inform an understanding of groundwater systems. These models, fundamental to understanding groundwater recharge, flow and discharge have found many uses as outlined in this paper.

Assessment of interactions between alluvial, Great Artesian Basin (GAB) and volcanic aquifers using 3D visualisation and environmental tracers, Lockyer Valley, southeast Queensland, Australia

A detailed 3D lithological model framework was developed using GOCAD software to understand interactions between alluvial, volcanic and GAB aquifers and the spatial and temporal distribution of groundwater recharge to the alluvium of the Lockyer Valley. Groundwater chemistry, isotope data (H20-δ2H and δ18O , 87Sr/86Sr, 3H and 14C) and groundwater level time-series data from approximately 550 observation wells were integrated into the catchment-wide 3D model to assess the recharge processes involved. This approach enabled the identification of zones where recharge to the alluvium primarily occurs from stream water during episodic flood events. Importantly, the study also demonstrates that in some sections of the alluvium recharge is also from storm rainfall and seepage discharge from the underlying GAB aquifers. These other sources of recharge are indicated by (a) the absence of a response of groundwater levels to flooding in some areas, (b) old radiocarbon ages, and (c) distinct bedrock water chemistry and δ2H and δ18O signatures in alluvial groundwater at these locations. Integration of isotopes, water chemistry and time-series displays of groundwater levels before and after the 2010/2011 flood into the 3D model suggest that the spatial variations in the alluvial groundwater response are mostly controlled by valley morphology and lithological (i.e. permeability) variations within the alluvium. Examination of the groundwater level variations in the 3D model also enabled quantification of the volumetric change of groundwater stored in the unconfined alluvial aquifer prior to and post-flood events.

Reconstructing 3D x-ray CT images of polymer gel dosimeters using the zero-scan method

In this study x-ray CT has been used to produce a 3D image of an irradiated PAGAT gel sample, with noise-reduction achieved using the ‘zero-scan’ method. The gel was repeatedly CT scanned and a linear fit to the varying Hounsfield unit of each pixel in the 3D volume was evaluated across the repeated scans, allowing a zero-scan extrapolation of the image to be obtained. To minimise heating of the CT scanner’s x-ray tube, this study used a large slice thickness (1 cm), to provide image slices across the irradiated region of the gel, and a relatively small number of CT scans (63), to extrapolate the zero-scan image. The resulting set of transverse images shows reduced noise compared to images from the initial CT scan of the gel, without being degraded by the additional radiation dose delivered to the gel during the repeated scanning. The full, 3D image of the gel has a low spatial resolution in the longitudinal direction, due to the selected scan parameters. Nonetheless, important features of the dose distribution are apparent in the 3D x-ray CT scan of the gel. The results of this study demonstrate that the zero-scan extrapolation method can be applied to the reconstruction of multiple x-ray CT slices, to provide useful 2D and 3D images of irradiated dosimetry gels.

Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity-modulated and volumetric-modulated arc radiotherapy

Introduction This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across 5 centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity-modulated radiotherapy (IMRT) and 47 treated with volumetric-modulated arc therapy (VMAT). Methods Treatment plan quality was evaluated in terms of target dose homogeneity and organ-at-risk sparing, through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each organ-at-risk. Statistical significance was evaluated using two-tailed Welch’s T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. Results The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the organs-at-risk: with increased compliance with recommended organ-at-risk dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. Conclusions This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT.

Evaluation of the spatial distribution of γH2AX following ionizing radiation

An early molecular response to DNA double-strand breaks (DSBs) is phosphorylation of the Ser-139 residue within the terminal SQEY motif of the histone H2AX1,2. This phosphorylation of H2AX is mediated by the phosphatidyl-inosito 3-kinase (PI3K) family of proteins, ataxia telangiectasia mutated (ATM), DNA-protein kinase catalytic subunit and ATM and RAD3-related (ATR)3. The phosphorylated form of H2AX, referred to as γH2AX, spreads to adjacent regions of chromatin from the site of the DSB, forming discrete foci, which are easily visualized by immunofluorecence microscopy3. Analysis and quantitation of γH2AX foci has been widely used to evaluate DSB formation and repair, particularly in response to ionizing radiation and for evaluating the efficacy of various radiation modifying compounds and cytotoxic compounds Given the exquisite specificity and sensitivity of this de novo marker of DSBs, it has provided new insights into the processes of DNA damage and repair in the context of chromatin. For example, in radiation biology the central paradigm is that the nuclear DNA is the critical target with respect to radiation sensitivity. Indeed, the general consensus in the field has largely been to view chromatin as a homogeneous template for DNA damage and repair. However, with the use of γH2AX as molecular marker of DSBs, a disparity in γ-irradiation-induced γH2AX foci formation in euchromatin and heterochromatin has been observed5-7. Recently, we used a panel of antibodies to either mono-, di- or tri- methylated histone H3 at lysine 9 (H3K9me1, H3K9me2, H3K9me3) which are epigenetic imprints of constitutive heterochromatin and transcriptional silencing and lysine 4 (H3K4me1, H3K4me2, H3K4me3), which are tightly correlated actively transcribing euchromatic regions, to investigate the spatial distribution of γH2AX following ionizing radiation8. In accordance with the prevailing ideas regarding chromatin biology, our findings indicated a close correlation between γH2AX formation and active transcription9. Here we demonstrate our immunofluorescence method for detection and quantitation of γH2AX foci in non-adherent cells, with a particular focus on co-localization with other epigenetic markers, image analysis and 3Dmodeling.

Modeling kinect sensor noise for improved 3D reconstruction and tracking

We contribute an empirically derived noise model for the Kinect sensor. We systematically measure both lateral and axial noise distributions, as a function of both distance and angle of the Kinect to an observed surface. The derived noise model can be used to filter Kinect depth maps for a variety of applications. Our second contribution applies our derived noise model to the KinectFusion system to extend filtering, volumetric fusion, and pose estimation within the pipeline. Qualitative results show our method allows reconstruction of finer details and the ability to reconstruct smaller objects and thinner surfaces. Quantitative results also show our method improves pose estimation accuracy. © 2012 IEEE.

3D cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer

Despite monolayer cultures being widely used for cancer drug development and testing, 2D cultures tend to be hypersensitive to chemotherapy and are relatively poor predictors of whether a drug will provide clinical benefit. Whilst generally more complicated, three dimensional (3D) culture systems often better recapitulate true cancer architecture and provide a more accurate drug response. As a step towards making 3D cancer cultures more accessible, we have developed a microwell platform and surface modification protocol to enable high throughput manufacture of 3D cancer aggregates. Herein we use this novel system to characterize prostate cancer cell microaggregates, including growth kinetics and drug sensitivity. Our results indicate that prostate cancer cells are viable in this system, however some non-cancerous prostate cell lines are not. This system allows us to consistently control for the presence or absence of an apoptotic core in the 3D cancer microaggregates. Similar to tumor tissues, the 3D microaggregates display poor polarity. Critically the response of 3D microaggregates to the chemotherapeutic drug, docetaxel, is more consistent with in vivo results than the equivalent 2D controls. Cumulatively, our results demonstrate that these prostate cancer microaggregates better recapitulate the morphology of prostate tumors compared to 2D and can be used for high-throughput drug testing.

Probabilistic multi-tensor estimation using the tensor distribution function

Diffusion weighted magnetic resonance (MR) imaging is a powerful tool that can be employed to study white matter microstructure by examining the 3D displacement profile of water molecules in brain tissue. By applying diffusion-sensitized gradients along a minimum of 6 directions, second-order tensors can be computed to model dominant diffusion processes. However, conventional DTI is not sufficient to resolve crossing fiber tracts. Recently, a number of high-angular resolution schemes with greater than 6 gradient directions have been employed to address this issue. In this paper, we introduce the Tensor Distribution Function (TDF), a probability function defined on the space of symmetric positive definite matrices. Here, fiber crossing is modeled as an ensemble of Gaussian diffusion processes with weights specified by the TDF. Once this optimal TDF is determined, the diffusion orientation distribution function (ODF) can easily be computed by analytic integration of the resulting displacement probability function.

The tensor distribution function

Diffusion weighted magnetic resonance imaging is a powerful tool that can be employed to study white matter microstructure by examining the 3D displacement profile of water molecules in brain tissue. By applying diffusion-sensitized gradients along a minimum of six directions, second-order tensors (represented by three-by-three positive definite matrices) can be computed to model dominant diffusion processes. However, conventional DTI is not sufficient to resolve more complicated white matter configurations, e.g., crossing fiber tracts. Recently, a number of high-angular resolution schemes with more than six gradient directions have been employed to address this issue. In this article, we introduce the tensor distribution function (TDF), a probability function defined on the space of symmetric positive definite matrices. Using the calculus of variations, we solve the TDF that optimally describes the observed data. Here, fiber crossing is modeled as an ensemble of Gaussian diffusion processes with weights specified by the TDF. Once this optimal TDF is determined, the orientation distribution function (ODF) can easily be computed by analytic integration of the resulting displacement probability function. Moreover, a tensor orientation distribution function (TOD) may also be derived from the TDF, allowing for the estimation of principal fiber directions and their corresponding eigenvalues.