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Sample records for 3d avascular tumors

  1. Numerical simulation of avascular tumor growth

    Slezak, D Fernandez; Suarez, C; Soba, A; Risk, M; Marshall, G [Laboratorio de Sistemas Complejos, Departamento de Computacion, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (C1428EGA) Buenos Aires (Argentina)

    2007-11-15

    A mathematical and numerical model for the description of different aspects of microtumor development is presented. The model is based in the solution of a system of partial differential equations describing an avascular tumor growth. A detailed second-order numeric algorithm for solving this system is described. Parameters are swiped to cover a range of feasible physiological values. While previous published works used a single set of parameters values, here we present a wide range of feasible solutions for tumor growth, covering a more realistic scenario. The model is validated by experimental data obtained with a multicellular spheroid model, a specific type of in vitro biological model which is at present considered to be optimum for the study of complex aspects of avascular microtumor physiology. Moreover, a dynamical analysis and local behaviour of the system is presented, showing chaotic situations for particular sets of parameter values at some fixed points. Further biological experiments related to those specific points may give potentially interesting results.

  2. A two-phase mixture model of avascular tumor growth

    Ozturk, Deniz; Burcin Unlu, M.; Yonucu, Sirin; Cetiner, Ugur

    2012-02-01

    Interactions with biological environment surrounding a growing tumor have major influence on tumor invasion. By recognizing that mechanical behavior of tumor cells could be described by biophysical laws, the research on physical oncology aims to investigate the inner workings of cancer invasion. In this study, we introduce a mathematical model of avascular tumor growth using the continuum theory of mixtures. Mechanical behavior of the tumor and physical interactions between the tumor and host tissue are represented by biophysically founded relationships. In this model, a solid tumor is embedded in inviscid interstitial fluid. The tumor has viscous mechanical properties. Interstitial fluid exhibits properties of flow through porous medium. Associated with the mixture saturation constraint, we introduce a Lagrange multiplier which represents hydrostatic pressure of the interstitial fluid. We solved the equations using Finite Element Method in two-dimensions. As a result, we have introduced a two-phase mixture model of avascular tumor growth that provided a flexible mathematical framework to include cells' response to mechanical aspects of the tumor microenvironment. The model could be extended to capture tumor-ECM interactions which would have profound influence on tumor invasion.

  3. ADT-3D Tumor Detection Assistant in 3D

    Jaime Lazcano Bello

    2008-12-01

    Full Text Available The present document describes ADT-3D (Three-Dimensional Tumor Detector Assistant, a prototype application developed to assist doctors diagnose, detect and locate tumors in the brain by using CT scan. The reader may find on this document an introduction to tumor detection; ADT-3D main goals; development details; description of the product; motivation for its development; result’s study; and areas of applicability.

  4. The Role of Oxygen in Avascular Tumor Growth.

    Grimes, David Robert; Kannan, Pavitra; McIntyre, Alan; Kavanagh, Anthony; Siddiky, Abul; Wigfield, Simon; Harris, Adrian; Partridge, Mike

    2016-01-01

    The oxygen status of a tumor has significant clinical implications for treatment prognosis, with well-oxygenated subvolumes responding markedly better to radiotherapy than poorly supplied regions. Oxygen is essential for tumor growth, yet estimation of local oxygen distribution can be difficult to ascertain in situ, due to chaotic patterns of vasculature. It is possible to avoid this confounding influence by using avascular tumor models, such as tumor spheroids, a much better approximation of realistic tumor dynamics than monolayers, where oxygen supply can be described by diffusion alone. Similar to in situ tumours, spheroids exhibit an approximately sigmoidal growth curve, often approximated and fitted by logistic and Gompertzian sigmoid functions. These describe the basic rate of growth well, but do not offer an explicitly mechanistic explanation. This work examines the oxygen dynamics of spheroids and demonstrates that this growth can be derived mechanistically with cellular doubling time and oxygen consumption rate (OCR) being key parameters. The model is fitted to growth curves for a range of cell lines and derived values of OCR are validated using clinical measurement. Finally, we illustrate how changes in OCR due to gemcitabine treatment can be directly inferred using this model. PMID:27088720

  5. Simulation of avascular tumor growth by agent-based game model involving phenotype-phenotype interactions.

    Chen, Yong; Wang, Hengtong; Zhang, Jiangang; Chen, Ke; Li, Yumin

    2015-01-01

    All tumors, both benign and metastatic, undergo an avascular growth stage with nutrients supplied by the surrounding tissue. This avascular growth process is much easier to carry out in more qualitative and quantitative experiments starting from tumor spheroids in vitro with reliable reproducibility. Essentially, this tumor progression would be described as a sequence of phenotypes. Using agent-based simulation in a two-dimensional spatial lattice, we constructed a composite growth model in which the phenotypic behavior of tumor cells depends on not only the local nutrient concentration and cell count but also the game among cells. Our simulation results demonstrated that in silico tumors are qualitatively similar to those observed in tumor spheroid experiments. We also found that the payoffs in the game between two living cell phenotypes can influence the growth velocity and surface roughness of tumors at the same time. Finally, this current model is flexible and can be easily extended to discuss other situations, such as environmental heterogeneity and mutation. PMID:26648395

  6. Efficient coarse simulation of a growing avascular tumor

    Kavousanakis, Michail E.; Liu, Ping; Boudouvis, Andreas G.; Lowengrub, John; Kevrekidis, Ioannis G.

    2013-01-01

    The subject of this work is the development and implementation of algorithms which accelerate the simulation of early stage tumor growth models. Among the different computational approaches used for the simulation of tumor progression, discrete stochastic models (e.g., cellular automata) have been widely used to describe processes occurring at the cell and subcell scales (e.g., cell-cell interactions and signaling processes). To describe macroscopic characteristics (e.g., morphology) of growing tumors, large numbers of interacting cells must be simulated. However, the high computational demands of stochastic models make the simulation of large-scale systems impractical. Alternatively, continuum models, which can describe behavior at the tumor scale, often rely on phenomenological assumptions in place of rigorous upscaling of microscopic models. This limits their predictive power. In this work, we circumvent the derivation of closed macroscopic equations for the growing cancer cell populations; instead, we construct, based on the so-called “equation-free” framework, a computational superstructure, which wraps around the individual-based cell-level simulator and accelerates the computations required for the study of the long-time behavior of systems involving many interacting cells. The microscopic model, e.g., a cellular automaton, which simulates the evolution of cancer cell populations, is executed for relatively short time intervals, at the end of which coarse-scale information is obtained. These coarse variables evolve on slower time scales than each individual cell in the population, enabling the application of forward projection schemes, which extrapolate their values at later times. This technique is referred to as coarse projective integration. Increasing the ratio of projection times to microscopic simulator execution times enhances the computational savings. Crucial accuracy issues arising for growing tumors with radial symmetry are addressed by

  7. Risk factors for avascular osteonecrosis in children with malignant tumors after thermochemotherapy

    Full text: In children with locally advanced malignant tumors or recurrences after first-line treatment, loco-regional deep hyperthermia (RHT) at temperatures between 42-44 oC and platinum-based chemotherapy ± radiotherapy were administered in order to facilitate complete surgical resection. Growing understanding and clinical experience with RHT techniques disclosed an increasing number of children achieving a long-term remission. Therefore, we have also to focus on risk factors for late sequelae. Based on the current data available, in our patient population the most important and severe complication after RHT is avascular osteonecrosis of the femoral head. Although this complication can also be found after chemo- and/or radiotherapy alone, RHT may also be a risk factor for this complication. Aseptic ON in children and adolescents in caused by an interruption of the capital femoris epiphysis blood supply. Most children present with mild or intermittent pain in the anterior thight and a limb. The pertinent early physical findings include antalgic gait; muscle spasm with mild restriction of motion, especially abduction and internal rotation. In order to determine whether RHT contributes to development of ON in our patient population, we compared different treatment parameters in children and adults. In this analysis 72 patients aged between 1 - 72 years (median 16,1 years) with pelvic malignancies were included. Twenty-four patients were male and 48 female. RHT was performed with 3 annular phased array applicators constructed in the same way (Sigma-30, -40 and -60, BSD 2000, Medical Corporation, Salt Lake City, Utah, USA). The number of heat sessions per patient was 2-30. Frequencies ranged between 87-140 MHz. Maximum power supply ranged between 130-1300 Watts (W). Five different age groups were assigned: 1-5 years (22 pts), 6-10 years (6 pts), 11-15 years (7 pts), 16-20 years (9 pts), > 20 years (27 pts). The number of heat sessions was subdivided in the following

  8. Engineering cancer microenvironments for in vitro 3-D tumor models

    Waseem Asghar

    2015-12-01

    Full Text Available The natural microenvironment of tumors is composed of extracellular matrix (ECM, blood vasculature, and supporting stromal cells. The physical characteristics of ECM as well as the cellular components play a vital role in controlling cancer cell proliferation, apoptosis, metabolism, and differentiation. To mimic the tumor microenvironment outside the human body for drug testing, two-dimensional (2-D and murine tumor models are routinely used. Although these conventional approaches are employed in preclinical studies, they still present challenges. For example, murine tumor models are expensive and difficult to adopt for routine drug screening. On the other hand, 2-D in vitro models are simple to perform, but they do not recapitulate natural tumor microenvironment, because they do not capture important three-dimensional (3-D cell–cell, cell–matrix signaling pathways, and multi-cellular heterogeneous components of the tumor microenvironment such as stromal and immune cells. The three-dimensional (3-D in vitro tumor models aim to closely mimic cancer microenvironments and have emerged as an alternative to routinely used methods for drug screening. Herein, we review recent advances in 3-D tumor model generation and highlight directions for future applications in drug testing.

  9. Automated 3D Brain Tumor Edema Segmentation in FLAIR MRI

    Dvořák, P.; Bartušek, Karel

    Vol. S1. Berlin : Springer-Verlag, 2013, s. 489. ISSN 1352-8661. [ESMRMB 2013. Congress. Tolouse (FR), 03.10.2013-05.10.2013] Institutional support: RVO:68081731 Keywords : Automated 3D * brain tumor edema segmentation * FLAIR MRI Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  10. Phase-field models for tumor growth uin the avascular phase

    Silva, Susana Patrícia Lopes Dias da

    2009-01-01

    Tumor é o crescimento anormal de uma massa de tecido resultante de várias divisões celulares sucessivas sem controlo, originadas por alteraçõoes no genoma do DNA da célula precurssora, ou seja esta célula inicial sofreu várias mutações. Para proliferar o tumor tem de vencer diversos factores externos, tais como o sistema imunitário do organismo que o considera um corpo estranho e tenta combatê-lo, a pressão exercida pela matriz extracelular e pelas células normais adjacen...

  11. Simulation of 3D tumor cell growth using nonlinear finite element method.

    Dong, Shoubing; Yan, Yannan; Tang, Liqun; Meng, Junping; Jiang, Yi

    2016-06-01

    We propose a novel parallel computing framework for a nonlinear finite element method (FEM)-based cell model and apply it to simulate avascular tumor growth. We derive computation formulas to simplify the simulation and design the basic algorithms. With the increment of the proliferation generations of tumor cells, the FEM elements may become larger and more distorted. Then, we describe a remesh and refinement processing of the distorted or over large finite elements and the parallel implementation based on Message Passing Interface to improve the accuracy and efficiency of the simulation. We demonstrate the feasibility and effectiveness of the FEM model and the parallelization methods in simulations of early tumor growth. PMID:26213205

  12. Brain tumor locating in 3D MR volume using symmetry

    Dvořák, Pavel; Bartušek, Karel

    Bellingham: SPIE, 2014, 903432:1-6. ISBN 978-0-8194-9827-4. ISSN 1605-7422. [Medical Imaging 2014: Image Processing . San Diego (US), 15.02.2014-20.02.2014] R&D Projects: GA ČR GAP102/12/1104; GA MŠk ED0017/01/01; GA MŠk(CZ) LO1212 Keywords : brain cancer * MRI * 3D MRI Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  13. Avascular Necrosis

    ... Kidney/Wilms Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid Cancer Understanding Children's Cancer Anxiety Around Procedures Childhood Cancer Statistics Late ...

  14. 3D-CT imaging processing for qualitative and quantitative analysis of maxillofacial cysts and tumors

    The objective of this study was to evaluate spiral-computed tomography (3D-CT) images of 20 patients presenting with cysts and tumors in the maxillofacial complex, in order to compare the surface and volume techniques of image rendering. The qualitative and quantitative appraisal indicated that the volume technique allowed a more precise and accurate observation than the surface method. On the average, the measurements obtained by means of the 3D volume-rendering technique were 6.28% higher than those obtained by means of the surface method. The sensitivity of the 3D surface technique was lower than that of the 3D volume technique for all conditions stipulated in the diagnosis and evaluation of lesions. We concluded that the 3D-CT volume rendering technique was more reproducible and sensitive than the 3D-CT surface method, in the diagnosis, treatment planning and evaluation of maxillofacial lesions, especially those with intra-osseous involvement. (author)

  15. XPO1 Inhibition Preferentially Disrupts the 3D Nuclear Organization of Telomeres in Tumor Cells.

    Taylor-Kashton, Cheryl; Lichtensztejn, Daniel; Baloglu, Erkan; Senapedis, William; Shacham, Sharon; Kauffman, Michael G; Kotb, Rami; Mai, Sabine

    2016-12-01

    Previous work has shown that the three-dimensional (3D) nuclear organization of telomeres is altered in cancer cells and the degree of alterations coincides with aggressiveness of disease. Nuclear pores are essential for spatial genome organization and gene regulation and XPO1 (exportin 1/CRM1) is the key nuclear export protein. The Selective Inhibitor of Nuclear Export (SINE) compounds developed by Karyopharm Therapeutics (KPT-185, KPT-330/selinexor, and KPT-8602) inhibit XPO1 nuclear export function. In this study, we investigated whether XPO1 inhibition has downstream effects on the 3D nuclear organization of the genome. This was assessed by measuring the 3D telomeric architecture of normal and tumor cells in vitro and ex vivo. Our data demonstrate for the first time a rapid and preferential disruption of the 3D nuclear organization of telomeres in tumor cell lines and in primary cells ex vivo derived from treatment-naïve newly diagnosed multiple myeloma patients. Normal primary cells in culture as well as healthy lymphocyte control cells from the same patients were minimally affected. Using both lymphoid and non-lymphoid tumor cell lines, we found that the downstream effects on the 3D nuclear telomere structure are independent of tumor type. We conclude that the 3D nuclear organization of telomeres is a sensitive indicator of cellular response when treated with XPO1 inhibitors. J. Cell. Physiol. 231: 2711-2719, 2016. © 2016 Wiley Periodicals, Inc. PMID:26991404

  16. Using a 3-d model system to screen for drugs effective on solid tumors

    Fayad, Walid

    2011-01-01

    There is a large medical need for the development of effective anticancer agents with minimal side effects. The present thesis represents an attempt to identify potent drugs for treatment of solid tumors. We used a strategy where 3-D multicellular tumor spheroids (cancer cells grown in three dimensional culture) were utilized as in vitro models for solid tumors. Drug libraries were screened using spheroids as targets and using apoptosis induction and loss of cell viability as endpoints. The h...

  17. Model-based risk assessment for motion effects in 3D radiotherapy of lung tumors

    Werner, René; Ehrhardt, Jan; Schmidt-Richberg, Alexander; Handels, Heinz

    2012-02-01

    Although 4D CT imaging becomes available in an increasing number of radiotherapy facilities, 3D imaging and planning is still standard in current clinical practice. In particular for lung tumors, respiratory motion is a known source of uncertainty and should be accounted for during radiotherapy planning - which is difficult by using only a 3D planning CT. In this contribution, we propose applying a statistical lung motion model to predict patients' motion patterns and to estimate dosimetric motion effects in lung tumor radiotherapy if only 3D images are available. Being generated based on 4D CT images of patients with unimpaired lung motion, the model tends to overestimate lung tumor motion. It therefore promises conservative risk assessment regarding tumor dose coverage. This is exemplarily evaluated using treatment plans of lung tumor patients with different tumor motion patterns and for two treatment modalities (conventional 3D conformal radiotherapy and step-&- shoot intensity modulated radiotherapy). For the test cases, 4D CT images are available. Thus, also a standard registration-based 4D dose calculation is performed, which serves as reference to judge plausibility of the modelbased 4D dose calculation. It will be shown that, if combined with an additional simple patient-specific breathing surrogate measurement (here: spirometry), the model-based dose calculation provides reasonable risk assessment of respiratory motion effects.

  18. Individualized Surgical Approach Planning for Petroclival Tumors Using a 3D Printer.

    Muelleman, Thomas John; Peterson, Jeremy; Chowdhury, Naweed Iffat; Gorup, Jason; Camarata, Paul; Lin, James

    2016-06-01

    Objectives To determine the utility of three-dimensional (3D) printed models in individualized petroclival tumor resection planning by measuring the fidelity of printed anatomical structures and comparing tumor exposure afforded by different approaches. Design Case series and review of the literature. Setting Tertiary care center. Participants Three patients with petroclival lesions. Main Outcome Measures Subjective opinion of access by neuro-otologists and neurosurgeons as well as surface area of tumor exposure. Results Surgeons found the 3D models of each patient's skull and tumor useful for preoperative planning. Limitations of individual surgical approaches not identified through preoperative imaging were apparent after 3D models were evaluated. Significant variability in exposure was noted between models for similar or identical approaches. A notable drawback is that our printing process did not replicate mastoid air cells. Conclusions We found that 3D modeling is useful for individualized preoperative planning for approaching petroclival tumors. Our printing techniques did produce authentic replicas of the tumors in relation to bony structures. PMID:27175320

  19. Digital holographic microscopy for imaging growth and treatment response in 3D tumor models

    Li, Yuyu; Petrovic, Ljubica; Celli, Jonathan P.; Yelleswarapu, Chandra S.

    2014-03-01

    While three-dimensional tumor models have emerged as valuable tools in cancer research, the ability to longitudinally visualize the 3D tumor architecture restored by these systems is limited with microscopy techniques that provide only qualitative insight into sample depth, or which require terminal fixation for depth-resolved 3D imaging. Here we report the use of digital holographic microscopy (DHM) as a viable microscopy approach for quantitative, non-destructive longitudinal imaging of in vitro 3D tumor models. Following established methods we prepared 3D cultures of pancreatic cancer cells in overlay geometry on extracellular matrix beds and obtained digital holograms at multiple timepoints throughout the duration of growth. The holograms were digitally processed and the unwrapped phase images were obtained to quantify nodule thickness over time under normal growth, and in cultures subject to chemotherapy treatment. In this manner total nodule volumes are rapidly estimated and demonstrated here to show contrasting time dependent changes during growth and in response to treatment. This work suggests the utility of DHM to quantify changes in 3D structure over time and suggests the further development of this approach for time-lapse monitoring of 3D morphological changes during growth and in response to treatment that would otherwise be impractical to visualize.

  20. The application of digital medical 3D printing technology on tumor operation

    Chen, Jimin; Jiang, Yijian; Li, Yangsheng

    2016-04-01

    Digital medical 3D printing technology is a new hi-tech which combines traditional medical and digital design, computer science, bio technology and 3D print technology. At the present time there are four levels application: The printed 3D model is the first and simple application. The surgery makes use of the model to plan the processing before operation. The second is customized operation tools such as implant guide. It helps doctor to operate with special tools rather than the normal medical tools. The third level application of 3D printing in medical area is to print artificial bones or teeth to implant into human body. The big challenge is the fourth level which is to print organs with 3D printing technology. In this paper we introduced an application of 3D printing technology in tumor operation. We use 3D printing to print guide for invasion operation. Puncture needles were guided by printed guide in face tumors operation. It is concluded that this new type guide is dominantly advantageous.

  1. 3D cell culture systems modeling tumor growth determinants in cancer target discovery.

    Thoma, Claudio R; Zimmermann, Miriam; Agarkova, Irina; Kelm, Jens M; Krek, Wilhelm

    2014-04-01

    Phenotypic heterogeneity of cancer cells, cell biological context, heterotypic crosstalk and the microenvironment are key determinants of the multistep process of tumor development. They sign responsible, to a significant extent, for the limited response and resistance of cancer cells to molecular-targeted therapies. Better functional knowledge of the complex intra- and intercellular signaling circuits underlying communication between the different cell types populating a tumor tissue and of the systemic and local factors that shape the tumor microenvironment is therefore imperative. Sophisticated 3D multicellular tumor spheroid (MCTS) systems provide an emerging tool to model the phenotypic and cellular heterogeneity as well as microenvironmental aspects of in vivo tumor growth. In this review we discuss the cellular, chemical and physical factors contributing to zonation and cellular crosstalk within tumor masses. On this basis, we further describe 3D cell culture technologies for growth of MCTS as advanced tools for exploring molecular tumor growth determinants and facilitating drug discovery efforts. We conclude with a synopsis on technological aspects for on-line analysis and post-processing of 3D MCTS models. PMID:24636868

  2. Modeling simulation and visualization of conformal 3D lung tumor dosimetry

    Lung tumors move during breathing depending on the patient's patho-physiological condition and orientation, thereby compromising the accurate deposition of the radiation dose during radiotherapy. In this paper, we present and validate a computer-based simulation framework to calculate the delivered dose to a 3D moving tumor and its surrounding normal tissues. The computer-based simulation framework models a 3D volumetric lung tumor and its surrounding tissues, simulates the tumor motion during a simulated dose delivery both as a self-reproducible motion and a random motion using the dose extracted from a treatment plan, and predicts the amount and location of radiation doses deposited. A radiation treatment plan of a small lung tumor (1-3 cm diameter) was developed in a commercial planning system (iPlan software, BrainLab, Munich, Germany) to simulate the radiation dose delivered. The dose for each radiation field was extracted from the software. The tumor motion was simulated for varying values of its rate, amplitude and direction within a single breath as well as from one breath to another. Such variations represent the variations in tumor motion induced by breathing variations. During the simulation of dose delivery, the dose on the target was summed to generate the real-time dose to the tumor for each beam independently. The simulation results show that the dose accumulated on the tumor varies significantly with both the tumor size and the tumor's motion rate, amplitude and direction. For a given tumor motion rate, amplitude and direction, the smaller the tumor size the smaller is the percentage of the radiation dose accumulated. The simulation results are validated by comparing the center plane of the 3D tumor with 2D film dosimetry measurements using a programmable 4D motion phantom moving in a self-reproducible pattern. The results also show the real-time capability of the framework at 40 discrete tumor motion steps per breath, which is higher than the

  3. 3-D in vivo brain tumor geometry study by scaling analysis

    Torres Hoyos, F.; Martín-Landrove, M.

    2012-02-01

    A new method, based on scaling analysis, is used to calculate fractal dimension and local roughness exponents to characterize in vivo 3-D tumor growth in the brain. Image acquisition was made according to the standard protocol used for brain radiotherapy and radiosurgery, i.e., axial, coronal and sagittal magnetic resonance T1-weighted images, and comprising the brain volume for image registration. Image segmentation was performed by the application of the k-means procedure upon contrasted images. We analyzed glioblastomas, astrocytomas, metastases and benign brain tumors. The results show significant variations of the parameters depending on the tumor stage and histological origin.

  4. Virtual 3D tumor marking-exact intraoperative coordinate mapping improve post-operative radiotherapy

    The quality of the interdisciplinary interface in oncological treatment between surgery, pathology and radiotherapy is mainly dependent on reliable anatomical three-dimensional (3D) allocation of specimen and their context sensitive interpretation which defines further treatment protocols. Computer-assisted preoperative planning (CAPP) allows for outlining macroscopical tumor size and margins. A new technique facilitates the 3D virtual marking and mapping of frozen sections and resection margins or important surgical intraoperative information. These data could be stored in DICOM format (Digital Imaging and Communication in Medicine) in terms of augmented reality and transferred to communicate patient's specific tumor information (invasion to vessels and nerves, non-resectable tumor) to oncologists, radiotherapists and pathologists

  5. Virtual 3D tumor marking-exact intraoperative coordinate mapping improve post-operative radiotherapy

    Essig Harald

    2011-11-01

    Full Text Available Abstract The quality of the interdisciplinary interface in oncological treatment between surgery, pathology and radiotherapy is mainly dependent on reliable anatomical three-dimensional (3D allocation of specimen and their context sensitive interpretation which defines further treatment protocols. Computer-assisted preoperative planning (CAPP allows for outlining macroscopical tumor size and margins. A new technique facilitates the 3D virtual marking and mapping of frozen sections and resection margins or important surgical intraoperative information. These data could be stored in DICOM format (Digital Imaging and Communication in Medicine in terms of augmented reality and transferred to communicate patient's specific tumor information (invasion to vessels and nerves, non-resectable tumor to oncologists, radiotherapists and pathologists.

  6. Detectability of hepatic tumors during 3D post-processed ultrafast cone-beam computed tomography

    To evaluate hepatic tumor detection using ultrafast cone-beam computed tomography (UCBCT) cross-sectional and 3D post-processed image datasets.657 patients were examined using UCBCT during hepatic transarterial chemoembolization (TACE), and data were collected retrospectively from January 2012 to September 2014. Tumor detectability, diagnostic ability, detection accuracy and sensitivity were examined for different hepatic tumors using UCBCT cross-sectional, perfusion blood volume (PBV) and UCBCT–MRI (magnetic resonance imaging) fused image datasets. Appropriate statistical tests were used to compare collected sample data.Fused image data showed the significantly higher (all P  <  0.05) diagnostic ability for hepatic tumors compared to UCBCT or PBV image data. The detectability of small hepatic tumors (<5 mm) was significantly reduced (all P  <  0.05) using UCBCT cross-sectional images compared to MRI or fused image data; however, PBV improved tumor detectability using a color display. Fused image data produced 100% tumor sensitivity due to the simultaneous availability of MRI and UCBCT information during tumor diagnosis.Fused image data produced excellent hepatic tumor sensitivity, detectability and diagnostic ability compared to other datasets assessed. Fused image data is extremely reliable and useful compared to UCBCT cross-sectional or PBV image datasets to depict hepatic tumors during TACE. Partial anatomical visualization on cross-sectional images was compensated by fused image data during tumor diagnosis. (paper)

  7. A novel asymmetric 3D in-vitro assay for the study of tumor cell invasion

    The induction of tumor cell invasion is an important step in tumor progression. Due to the cost and slowness of in-vivo invasion assays, there is need for quantitative in-vitro invasion assays that mimic as closely as possible the tumor environment and in which conditions can be rigorously controlled. We have established a novel asymmetric 3D in-vitro invasion assay by embedding a monolayer of tumor cells between two layers of collagen. The cells were then allowed to invade the upper and lower layers of collagen. To visualize invading cells the gels were sectioned perpendicular to the monolayer so that after seeding the monolayer appears as a thin line precisely defining the origin of invasion. The number of invading tumor cells, their proliferation rate, the distance they traverse and the direction of invasion could then be determined quantitatively. The assay was used to compare the invasive properties of several tumor cell types and the results compare well with those obtained by previously described assays. Lysyl-oxidase like protein-2 (Loxl2) is a potent inducer of invasiveness. Using our assay we show for the first time that inhibition of endogenous Loxl2 expression in several types of tumor cells strongly inhibits their invasiveness. We also took advantage of the asymmetric nature of the assay in order to show that fibronectin enhances the invasiveness of breast cancer cells more potently than laminin. The asymmetric properties of the assay were also used to demonstrate that soluble factors derived from fibroblasts can preferentially attract invading breast cancer cells. Our assay displays several advantages over previous invasion assays as it is allows the quantitative analysis of directional invasive behavior of tumor cells in a 3D environment mimicking the tumor microenvironment. It should be particularly useful for the study of the effects of components of the tumor microenvironment on tumor cell invasiveness

  8. 3D printer generated thorax phantom with mobile tumor for radiation dosimetry

    Mayer, Rulon; Liacouras, Peter; Thomas, Andrew; Kang, Minglei; Lin, Liyong; Simone, Charles B.

    2015-07-01

    This article describes the design, construction, and properties of an anthropomorphic thorax phantom with a moving surrogate tumor. This novel phantom permits detection of dose both inside and outside a moving tumor and within the substitute lung tissue material. A 3D printer generated the thorax shell composed of a chest wall, spinal column, and posterior regions of the phantom. Images of a computed tomography scan of the thorax from a patient with lung cancer provided the template for the 3D printing. The plastic phantom is segmented into two materials representing the muscle and bones, and its geometry closely matches a patient. A surrogate spherical plastic tumor controlled by a 3D linear stage simulates a lung tumor's trajectory during normal breathing. Sawdust emulates the lung tissue in terms of average and distribution in Hounsfield numbers. The sawdust also provides a forgiving medium that permits tumor motion and sandwiching of radiochromic film inside the mobile surrogate plastic tumor for dosimetry. A custom cork casing shields the film and tumor and eliminates film bending during extended scans. The phantom, lung tissue surrogate, and radiochromic film are exposed to a seven field plan based on an ECLIPSE plan for 6 MV photons from a Trilogy machine delivering 230 cGy to the isocenter. The dose collected in a sagittal plane is compared to the calculated plan. Gamma analysis finds 8.8% and 5.5% gamma failure rates for measurements of large amplitude trajectory and static measurements relative to the large amplitude plan, respectively. These particular gamma analysis results were achieved using parameters of 3% dose and 3 mm, for regions receiving doses >150 cGy. The plan assumes a stationary detection grid unlike the moving radiochromic film and tissues. This difference was experimentally observed and motivated calculated dose distributions that incorporated the phase of the tumor periodic motion. These calculations modestly improve agreement between

  9. Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

    Hui Guo

    2016-07-01

    Full Text Available Evodiamine (EVO and rutaecarpine (RUT are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids, and compared the results with those obtained from 2D monolayers. The drugs’ IC50 values were significantly increased from the range of 6.4–44.1 μM in 2D monolayers to 21.8–138.0 μM in 3D multicellular spheroids, which may be due to enhanced mass barrier and reduced drug penetration in 3D models. The fluorescence of EVO and RUT was measured via fluorescence spectroscopy and the cellular uptake of both drugs was characterized in 2D tumor models. The results showed that the cellular uptake concentrations of RUT increased with increasing drug concentrations. However, the EVO concentrations uptaken by the cells showed only a small change with increasing drug concentrations, which may be due to the different solubility of EVO and Rut in solvents. Overall, this study provided a new vision of the anti-tumor activity of EVO and RUT via 3D multicellular spheroids and cellular uptake through the fluorescence of compounds.

  10. Antiproliferative Activity and Cellular Uptake of Evodiamine and Rutaecarpine Based on 3D Tumor Models

    Hui Guo; Dongmei Liu; Bin Gao; Xiaohui Zhang; Minli You; Hui Ren; Hongbo Zhang; Santos, Hélder A.; Feng Xu

    2016-01-01

    Evodiamine (EVO) and rutaecarpine (RUT) are promising anti-tumor drug candidates. The evaluation of the anti-proliferative activity and cellular uptake of EVO and RUT in 3D multicellular spheroids of cancer cells would better recapitulate the native situation and thus better reflect an in vivo response to the treatment. Herein, we employed the 3D culture of MCF-7 and SMMC-7721 cells based on hanging drop method and evaluated the anti-proliferative activity and cellular uptake of EVO and RUT i...

  11. Conventional (2D) Versus Conformal (3D) Techniques in Radiotherapy for Malignant Pediatric Tumors: Dosimetric Perspectives

    Objectives: In pediatric radiotherapy, the enhanced radiosensitivity of the developing tissues combined with the high overall survival, raise the possibility of late complications. The present study aims at comparing two dimensional (2D) and three dimensional (3D) planning regarding dose homogeneity within target volume and dose to organs at risk (OARs) to demonstrate the efficacy of 3D in decreasing dose to normal tissue. Material and Methods: Thirty pediatric patients (18 years or less) with different pediatric tumors were planned using 2D and 3D plans. All were CT scanned after proper positioning and immobilization. Structures were contoured; including the planning target volume (PTV) and organs at risk (OARs). Conformal beams were designed and dose distribution analysis was edited to provide the best dose coverage to the PTV while sparing OARs using dose volume histograms (DVHs) of outlined structures. For the same PTVs conventional plans were created using the conventional simulator data (2-4 coplanar fields). Conventional and 3D plans coverage and distribution were compared using the term of V95% (volume of PTV receiving 95% of the prescribed dose), V107% (volume of PTV receiving 107% of the prescribed dose), and conformity index (CI) (volume receiving 90% of the prescribed dose/PTV). Doses received by OARs were compared in terms of mean dose. In children treated for brain lesions, OAR volume received 90% of the dose (V 90%) and OAR score were calculated. Results: The PTV coverage showed no statistical difference between 2D and 3D radiotherapy in terms of V95% or V107%. However, there was more conformity in 3D planning with CI 1.43 rather than conventional planning with CI 1.86 (p-value <0.001). Regarding OARs, 3D planning shows large gain in healthy tissue sparing. There was no statistical difference in mean dose received by each OAR. However, for brain cases, brain stem mean dose and brain V 90% showed better sparing in 3D planning (brain stem mean dose was

  12. 3D printer generated thorax phantom with mobile tumor for radiation dosimetry

    Mayer, Rulon [Henry Jackson Foundation, Bethesda, Maryland 20817 (United States); Liacouras, Peter [Walter Reed National Military Medical Center, Bethesda, Maryland 20899 (United States); Thomas, Andrew [ATC Healthcare, Washington, District of Columbia 20006 (United States); Kang, Minglei; Lin, Liyong; Simone, Charles B. [Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States)

    2015-07-15

    This article describes the design, construction, and properties of an anthropomorphic thorax phantom with a moving surrogate tumor. This novel phantom permits detection of dose both inside and outside a moving tumor and within the substitute lung tissue material. A 3D printer generated the thorax shell composed of a chest wall, spinal column, and posterior regions of the phantom. Images of a computed tomography scan of the thorax from a patient with lung cancer provided the template for the 3D printing. The plastic phantom is segmented into two materials representing the muscle and bones, and its geometry closely matches a patient. A surrogate spherical plastic tumor controlled by a 3D linear stage simulates a lung tumor’s trajectory during normal breathing. Sawdust emulates the lung tissue in terms of average and distribution in Hounsfield numbers. The sawdust also provides a forgiving medium that permits tumor motion and sandwiching of radiochromic film inside the mobile surrogate plastic tumor for dosimetry. A custom cork casing shields the film and tumor and eliminates film bending during extended scans. The phantom, lung tissue surrogate, and radiochromic film are exposed to a seven field plan based on an ECLIPSE plan for 6 MV photons from a Trilogy machine delivering 230 cGy to the isocenter. The dose collected in a sagittal plane is compared to the calculated plan. Gamma analysis finds 8.8% and 5.5% gamma failure rates for measurements of large amplitude trajectory and static measurements relative to the large amplitude plan, respectively. These particular gamma analysis results were achieved using parameters of 3% dose and 3 mm, for regions receiving doses >150 cGy. The plan assumes a stationary detection grid unlike the moving radiochromic film and tissues. This difference was experimentally observed and motivated calculated dose distributions that incorporated the phase of the tumor periodic motion. These calculations modestly improve agreement between

  13. 3D printer generated thorax phantom with mobile tumor for radiation dosimetry

    This article describes the design, construction, and properties of an anthropomorphic thorax phantom with a moving surrogate tumor. This novel phantom permits detection of dose both inside and outside a moving tumor and within the substitute lung tissue material. A 3D printer generated the thorax shell composed of a chest wall, spinal column, and posterior regions of the phantom. Images of a computed tomography scan of the thorax from a patient with lung cancer provided the template for the 3D printing. The plastic phantom is segmented into two materials representing the muscle and bones, and its geometry closely matches a patient. A surrogate spherical plastic tumor controlled by a 3D linear stage simulates a lung tumor’s trajectory during normal breathing. Sawdust emulates the lung tissue in terms of average and distribution in Hounsfield numbers. The sawdust also provides a forgiving medium that permits tumor motion and sandwiching of radiochromic film inside the mobile surrogate plastic tumor for dosimetry. A custom cork casing shields the film and tumor and eliminates film bending during extended scans. The phantom, lung tissue surrogate, and radiochromic film are exposed to a seven field plan based on an ECLIPSE plan for 6 MV photons from a Trilogy machine delivering 230 cGy to the isocenter. The dose collected in a sagittal plane is compared to the calculated plan. Gamma analysis finds 8.8% and 5.5% gamma failure rates for measurements of large amplitude trajectory and static measurements relative to the large amplitude plan, respectively. These particular gamma analysis results were achieved using parameters of 3% dose and 3 mm, for regions receiving doses >150 cGy. The plan assumes a stationary detection grid unlike the moving radiochromic film and tissues. This difference was experimentally observed and motivated calculated dose distributions that incorporated the phase of the tumor periodic motion. These calculations modestly improve agreement between

  14. Renal Tumor Cryoablation Planning. The Efficiency of Simulation on Reconstructed 3D CT Scan

    Ciprian Valerian LUCAN

    2010-12-01

    Full Text Available Introduction & Objective: Nephron-sparing surgical techniques risks are related to tumor relationships with adjacent anatomic structures. Complexity of the renal anatomy drives the interest to develop tools for 3D reconstruction and surgery simulation. The aim of the article was to assess the simulation on reconstructed 3D CT scan used for planning the cryoablation. Material & Method: A prospective randomized study was performed between Jan. 2007 and July 2009 on 27 patients who underwent retroperitoneoscopic T1a renal tumors cryoablation (RC. All patients were assessed preoperatively by CT scan, also used for 3D volume rendering. In the Gr.A, the patients underwent surgery planning by simulation on 3D CT scan. In the Gr.B., patients underwent standard RC. The two groups were compared in terms of surgical time, bleeding, postoperative drainage, analgesics requirement, hospital stay, time to socio-professional reintegration. Results: Fourteen patients underwent preoperative cryoablation planning (Gr.A and 13 patients underwent standard CR (Gr.B. All parameters analyzed were shorter in the Gr.A. On multivariate logistic regression, only shortens of the surgical time (138.79±5.51 min. in Gr.A. vs. 140.92±5.54 min in Gr.B. and bleeding (164.29±60.22 mL in Gr.A. vs. 215.38±100.80 mL in Gr.B. achieved statistical significance (p<0.05. The number of cryoneedles assessed by simulation had a 92.52% accuracy when compared with those effectively used. Conclusions: Simulation of the cryoablation using reconstructed 3D CT scan improves the surgical results. The application used for simulation was able to accurately assess the number of cryoneedles required for tumor ablation, their direction and approach.

  15. Recovering 3D tumor locations from 2D bioluminescence images and registration with CT images

    Huang, Xiaolei; Metaxas, Dimitris N.; Menon, Lata G.; Mayer-Kuckuk, Philipp; Bertino, Joseph R.; Banerjee, Debabrata

    2006-02-01

    In this paper, we introduce a novel and efficient algorithm for reconstructing the 3D locations of tumor sites from a set of 2D bioluminescence images which are taken by a same camera but after continually rotating the object by a small angle. Our approach requires a much simpler set up than those using multiple cameras, and the algorithmic steps in our framework are efficient and robust enough to facilitate its use in analyzing the repeated imaging of a same animal transplanted with gene marked cells. In order to visualize in 3D the structure of the tumor, we also co-register the BLI-reconstructed crude structure with detailed anatomical structure extracted from high-resolution microCT on a single platform. We present our method using both phantom studies and real studies on small animals.

  16. Contrast-enhanced 3D ultrasound in the radiofrequency ablation of liver tumors

    Edward Leen; Senthil Kumar; Shahid A Khan; Gavin Low; Keh Oon Ong; Paul Tait; Mike Averkiou

    2009-01-01

    Liver metastases and hepatocellular carcinomas are two of the most common causes of cancer deaths in the world. Radiofrequency ablation (RFA) is a well recognized, effective and minimally invasive means of treating malignant hepatic tumors. This article describes the use of contrast-enhanced 3D ultrasound (CE-3DUS) in the staging, targeting and followup of patients with liver tumors undergoing RFA. In particular, its value in the management of large hepatic lesions will be illustrated. Current limitations of CE-3DUS and future developments in the technique will also be discussed. In summary, CE-3DUS is useful in the RFA of liver tumors with improved detection and display of occult lesions and recurrence, in the assessment of lesional geometry and orientation for a more accurate planning and guidance of multiple RFA needle electrodes in large tumors and in the evaluation of residual or recurrent disease within the immediate and/or subsequent follow-up periods.

  17. Generation of a tumor spheroid in a microgravity environment as a 3D model of melanoma.

    Marrero, Bernadette; Messina, Jane L; Heller, Richard

    2009-10-01

    An in vitro 3D model was developed utilizing a synthetic microgravity environment to facilitate studying the cell interactions. 2D monolayer cell culture models have been successfully used to understand various cellular reactions that occur in vivo. There are some limitations to the 2D model that are apparent when compared to cells grown in a 3D matrix. For example, some proteins that are not expressed in a 2D model are found up-regulated in the 3D matrix. In this paper, we discuss techniques used to develop the first known large, free-floating 3D tissue model used to establish tumor spheroids. The bioreactor system known as the High Aspect Ratio Vessel (HARVs) was used to provide a microgravity environment. The HARVs promoted aggregation of keratinocytes (HaCaT) that formed a construct that served as scaffolding for the growth of mouse melanoma. Although there is an emphasis on building a 3D model with the proper extracellular matrix and stroma, we were able to develop a model that excluded the use of matrigel. Immunohistochemistry and apoptosis assays provided evidence that this 3D model supports B16.F10 cell growth, proliferation, and synthesis of extracellular matrix. Immunofluorescence showed that melanoma cells interact with one another displaying observable cellular morphological changes. The goal of engineering a 3D tissue model is to collect new information about cancer development and develop new potential treatment regimens that can be translated to in vivo models while reducing the use of laboratory animals. PMID:19533253

  18. Characteristics of tumor and host cells in 3-D simulated microgravity environment

    Chopra, V.; Dinh, T.; Wood, T.; Pellis, N.; Hannigan, E.

    Co-cultures of three-dimensional (3-D) constructs of one cell type with dispersed cells of a second cell type in low-shear rotating suspension cultures in simulated microgravity environment have been used to investigate invasive properties of normal and malignant cell types. We have shown that the epithelial and endothelial cells undergo a switch in characteristics when grown in an in vitro 3-D environment, that mimics the in vivo host environment as compared with conventional two-dimensional (2-D) monolayer cultures. Histological preparations and immunohistochemical staining procedures of cocultured harvests demonstrated various markers of interest: like collagen vimentin, mucin, elastin, fibrin, fibrinogen, cytokeratin, adhesion molecules and various angiogenic factors by tumor cells from gynecological cancer patients along with fibroblasts, endothelial cells and patient-derived mononuclear cells (n=8). The growth rate was enhanced 10-15 folds by 3-D cocultures of patient-derived cells as compared with 2-D monolayer cultures and 3-D monocultures. The production of interleukin-2, interleukin-6, interleukin -8, vascular endothelial cell growth factor, basic fibroblast growth factor, and angiogenin was studied by using ELISA and RT- PCR. Human umbilical vein-derived endothelial cell (HUVEC) were used to study the mitogenic response of the conditioned medium collected from 3-D monocultures and cocultures during proliferation and migration assays. The conditioned medium collected from 3-D cocultures of cancer cells also 1) increased the expression of message levels of vascular endothelial growth factor and its receptor flt-1 and KDR was observed by HUVEC, and 2) increased the expression of intracellular and vascular cell adhesion molecules on the surface of HUVEC, when measured by using Live cell ELISA assays and immunofluorescent staining as compared with 3-D monocultures of normal epithelial cells. There was an increase in production of 1) enzymatic activity that

  19. Modeling tumor/polyp/lesion structure in 3D for computer-aided diagnosis in colonoscopy

    Chen, Chao-I.; Sargent, Dusty; Wang, Yuan-Fang

    2010-02-01

    We describe a software system for building three-dimensional (3D) models from colonoscopic videos. The system is end-to-end in the sense that it takes as input raw image frames-shot during a colon exam-and produces the 3D structure of objects of interest (OOI), such as tumors, polyps, and lesions. We use the structure-from-motion (SfM) approach in computer vision which analyzes an image sequence in which camera's position and aim vary relative to the OOI. The varying pose of the camera relative to the OOI induces the motion-parallax effect which allows 3D depth of the OOI to be inferred. Unlike the traditional SfM system pipeline, our software system contains many check-and-balance mechanisms to ensure robustness, and the analysis from earlier stages of the pipeline is used to guide the later processing stages to better handle challenging medical data. The constructed 3D models allow the pathology (growth and change in both structure and appearance) to be monitored over time.

  20. 3-D-conformal radiation therapy for pediatric giant cell tumors of the skull base

    Hug, E.B. [Massachusetts General Hospital, Boston, MA (United States). Dept. of Radiation Oncology; Harvard Univ., Cambridge, MA (United States). Cyclotron Lab.; Dartmouth Hitchcock Medical Center, Lebanon, NH (United States). Section of Radiation Oncology; Muenter, M.W.; Vries, A. de [Massachusetts General Hospital, Boston, MA (United States). Dept. of Radiation Oncology; Adams, J.A.; Munzenrider, J.E. [Massachusetts General Hospital, Boston, MA (United States). Dept. of Radiation Oncology; Harvard Univ., Cambridge, MA (United States). Cyclotron Lab.; Rosenberg, A.E. [Massachusetts General Hospital, Boston, MA (United States). Dept. of Pathology

    2002-05-01

    Background: Giant cell tumors (GCT) of the base of skull are rare neoplasms. This report reviews the treatment of four pediatric patients presenting with aggressive giant cell tumor, using fractionated and combined, conformal proton and photon radiation therapy at Massachusetts General Hospital and Harvard Cyclotron Laboratory. Patients and Methods: Three female patients and one adolescent male, ages 10-15 years, had undergone prior, extensive surgical resection(s) and were treated for either primary (two patients) or recurrent (two patients) disease. Gross residual tumor was evident in three patients and microscopic disease suspected in one patient. Combined proton and photon radiation theory was based on three-dimensional (3-D) planning, consisting of fractionated treatment, one fraction per day at 1.8 CGE (cobalt-gray equivalent) to total target doses of 57.6, 57.6, 59.4, and 61.2 Gy/CGE. Results: With observation times of 3.1 years, 3.3, 5.3, and 5.8 years, all four patients were alive and well and remained locally controlled without evidence of recurrent disease. Except for one patient with partial pituitary insufficiency following radiotherapy for sellar recurrent disease, thus far no late effects attributable to radiation therapy have been observed. Conclusions: 3-D conformal radiation therapy offers a realistic chance of tumor control for aggressive giant cell tumor in the skull base, either postoperatively or at time of recurrence. Conformal treatment techniques allow the safe delivery of relatively high radiation doses in the pediatric patient without apparent increase of side effects. (orig.)

  1. Biologically relevant 3D tumor arrays: treatment response and the importance of stromal partners

    Rizvi, Imran; Celli, Jonathan P.; Xu, Feng; Evans, Conor L.; Abu-Yousif, Adnan O.; Muzikansky, Alona; Elrington, Stefan A.; Pogue, Brian W.; Finkelstein, Dianne M.; Demirci, Utkan; Hasan, Tayyaba

    2011-02-01

    The development and translational potential of therapeutic strategies for cancer is limited, in part, by a lack of biological models that capture important aspects of tumor growth and treatment response. It is also becoming increasingly evident that no single treatment will be curative for this complex disease. Rationally-designed combination regimens that impact multiple targets provide the best hope of significantly improving clinical outcomes for cancer patients. Rapidly identifying treatments that cooperatively enhance treatment efficacy from the vast library of candidate interventions is not feasible, however, with current systems. There is a vital, unmet need to create cell-based research platforms that more accurately mimic the complex biology of human tumors than monolayer cultures, while providing the ability to screen therapeutic combinations more rapidly than animal models. We have developed a highly reproducible in vitro three-dimensional (3D) tumor model for micrometastatic ovarian cancer (OvCa), which in conjunction with quantitative image analysis routines to batch-process large datasets, serves as a high throughput reporter to screen rationally-designed combination regimens. We use this system to assess mechanism-based combination regimens with photodynamic therapy (PDT), which sensitizes OvCa to chemo and biologic agents, and has shown promise in clinic trials. We show that PDT synergistically enhances carboplatin efficacy in a sequence dependent manner. In printed heterocellular cultures we demonstrate that proximity of fibroblasts enhances 3D tumor growth and investigate co-cultures with endothelial cells. The principles described here could inform the design and evaluation of mechanism-based therapeutic options for a broad spectrum of metastatic solid tumors.

  2. Metabolic approach for tumor delineation in glioma surgery: 3D MR spectroscopy image-guided resection.

    Zhang, Jie; Zhuang, Dong-Xiao; Yao, Cheng-Jun; Lin, Ching-Po; Wang, Tian-Liang; Qin, Zhi-Yong; Wu, Jin-Song

    2016-06-01

    OBJECT The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy ((1)H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D (1)H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection. METHODS Choline (Cho)-N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D (1)H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection. RESULTS Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional (1)H-MRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D (1)H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection. PMID:26636387

  3. Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D

    MultiCellular Tumor Spheroid (MCTS) mimics the organization of a tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization and the activation of cell cycle checkpoints in 3D. Cell cycle and proliferation parameters were investigated in Capan-2 spheroids by immunofluorescence staining, EdU incorporation and using cells engineered to express Fucci-red and -green reporters. We describe in details the changes in proliferation and cell cycle parameters during spheroid growth and regionalization. We report the kinetics and regionalized aspects of cell cycle arrest in response to checkpoint activation induced by EGF starvation, lovastatin treatment and etoposide-induced DNA damage. Our data present the power and the limitation of spheroids made of genetically modified cells to explore cell cycle checkpoints. This study paves the way for the investigation of molecular aspects and dynamic studies of the response to novel antiproliferative agents in 3D models

  4. Correlation between the respiratory waveform measured using a respiratory sensor and 3D tumor motion in gated radiotherapy

    Purpose: The purpose of this study is to investigate the correlation between the respiratory waveform measured using a respiratory sensor and three-dimensional (3D) tumor motion. Methods and materials: A laser displacement sensor (LDS: KEYENCE LB-300) that measures distance using infrared light was used as the respiratory sensor. This was placed such that the focus was in an area around the patient's navel. When the distance from the LDS to the body surface changes as the patient breathes, the displacement is detected as a respiratory waveform. To obtain the 3D tumor motion, a biplane digital radiography unit was used. For the tumor in the lung, liver, and esophagus of 26 patients, the waveform was compared with the 3D tumor motion. The relationship between the respiratory waveform and the 3D tumor motion was analyzed by means of the Fourier transform and a cross-correlation function. Results: The respiratory waveform cycle agreed with that of the cranial-caudal and dorsal-ventral tumor motion. A phase shift observed between the respiratory waveform and the 3D tumor motion was principally in the range 0.0 to 0.3 s, regardless of the organ being measured, which means that the respiratory waveform does not always express the 3D tumor motion with fidelity. For this reason, the standard deviation of the tumor position in the expiration phase, as indicated by the respiratory waveform, was derived, which should be helpful in suggesting the internal margin required in the case of respiratory gated radiotherapy. Conclusion: Although obtained from only a few breathing cycles for each patient, the correlation between the respiratory waveform and the 3D tumor motion was evident in this study. If this relationship is analyzed carefully and an internal margin is applied, the accuracy and convenience of respiratory gated radiotherapy could be improved by use of the respiratory sensor.Thus, it is expected that this procedure will come into wider use

  5. A novel 3-D mineralized tumor model to study breast cancer bone metastasis.

    Siddharth P Pathi

    Full Text Available BACKGROUND: Metastatic bone disease is a frequent cause of morbidity in patients with advanced breast cancer, but the role of the bone mineral hydroxyapatite (HA in this process remains unclear. We have developed a novel mineralized 3-D tumor model and have employed this culture system to systematically investigate the pro-metastatic role of HA under physiologically relevant conditions in vitro. METHODOLOGY/PRINCIPAL FINDINGS: MDA-MB231 breast cancer cells were cultured within non-mineralized or mineralized polymeric scaffolds fabricated by a gas foaming-particulate leaching technique. Tumor cell adhesion, proliferation, and secretion of pro-osteoclastic interleukin-8 (IL-8 was increased in mineralized tumor models as compared to non-mineralized tumor models, and IL-8 secretion was more pronounced for bone-specific MDA-MB231 subpopulations relative to lung-specific breast cancer cells. These differences were pathologically significant as conditioned media collected from mineralized tumor models promoted osteoclastogenesis in an IL-8 dependent manner. Finally, drug testing and signaling studies with transforming growth factor beta (TGFbeta confirmed the clinical relevance of our culture system and revealed that breast cancer cell behavior is broadly affected by HA. CONCLUSIONS/SIGNIFICANCE: Our results indicate that HA promotes features associated with the neoplastic and metastatic growth of breast carcinoma cells in bone and that IL-8 may play an important role in this process. The developed mineralized tumor models may help to reveal the underlying cellular and molecular mechanisms that may ultimately enable more efficacious therapy of patients with advanced breast cancer.

  6. Clinical evaluation of 3D/3D MRI-CBCT automatching on brain tumors for online patient setup verification - A step towards MRI-based treatment planning

    Buhl, Sune K.; Duun-Christensen, Anne Katrine; Kristensen, Brian H.;

    2010-01-01

    undergoing postoperative radiotherapy for malignant brain tumors received a weekly CBCT. In total 18 scans was matched with both CT and MRI as reference. The CBCT scans were acquired using a Clinac iX 2300 linear accelerator (Varian Medical Systems) with an On-Board Imager (OBI). Results. For the phantom......Background. Magnetic Resonance Imaging (MRI) is often used in modern day radiotherapy (RT) due to superior soft tissue contrast. However, treatment planning based solely on MRI is restricted due to e. g. the limitations of conducting online patient setup verification using MRI as reference. In this...... study 3D/3D MRI-Cone Beam CT (CBCT) automatching for online patient setup verification was investigated. Material and methods. Initially, a multi-modality phantom was constructed and used for a quantitative comparison of CT-CBCT and MRI-CBCT automatching. Following the phantom experiment three patients...

  7. Dosimetry in brain tumor phantom at 15 MV 3D conformal radiation therapy

    Glioblastoma multiforme (GBM) is the most common, aggressive, highly malignant and infiltrative of all brain tumors with low rate of control. The main goal of this work was to evaluate the spatial dose distribution into a GBM simulator inside a head phantom exposed to a 15 MV 3D conformal radiation therapy in order to validate internal doses. A head and neck phantom developed by the Ionizing Radiation Research Group (NRI) was used on the experiments. Such phantom holds the following synthetic structures: brain and spinal cord, skull, cervical and thoracic vertebrae, jaw, hyoid bone, laryngeal cartilages, head and neck muscles and skin. Computer tomography (CT) of the simulator was taken, capturing a set of contrasted references. Therapy Radiation planning (TPS) was performed based on those CT images, satisfying a 200 cGy prescribed dose split in three irradiation fields. The TPS assumed 97% of prescribed dose cover the prescribed treatment volume (PTV). Radiochromic films in a solid water phantom provided dose response as a function of optical density. Spatial dosimetric distribution was generated by radiochromic film samples at coronal, sagittal-anterior and sagittal-posterior positions, inserted into tumor simulator and brain. The spatial dose profiles held 70 to 120% of the prescribed dose. In spite of the stratified profile, as opposed to the smooth dose profile from TPS, the tumor internal doses were within a 5% deviation from 214.4 cGy evaluated by TPS. 83.2% of the points with a gamma value of less than 1 (3%/3mm) for TPS and experimental values, respectively. At the tumor, measured at coronal section, a few dark spots in the film caused the appearance of outlier points in 13-15% of dose deviation percentage. And, as final conclusion, such dosimeter choice and the physical anthropomorphic and anthropometric phantom provided an efficient method for validating radiotherapy protocols

  8. 3D tumor localization through real-time volumetric x-ray imaging for lung cancer radiotherapy

    Li, Ruijiang; Jia, Xun; Gu, Xuejun; Folkerts, Michael; Men, Chunhua; Song, William Y; Jiang, Steve B

    2011-01-01

    Recently we have developed an algorithm for reconstructing volumetric images and extracting 3D tumor motion information from a single x-ray projection. We have demonstrated its feasibility using a digital respiratory phantom with regular breathing patterns. In this work, we present a detailed description and a comprehensive evaluation of the improved algorithm. The algorithm was improved by incorporating respiratory motion prediction. The accuracy and efficiency were then evaluated on 1) a digital respiratory phantom, 2) a physical respiratory phantom, and 3) five lung cancer patients. These evaluation cases include both regular and irregular breathing patterns that are different from the training dataset. For the digital respiratory phantom with regular and irregular breathing, the average 3D tumor localization error is less than 1 mm. On an NVIDIA Tesla C1060 GPU card, the average computation time for 3D tumor localization from each projection ranges between 0.19 and 0.26 seconds, for both regular and irreg...

  9. 3D reconstruction of breast tumors from ultrasonic cross-sectional images, using fuzzy reasoning and the marching cubes algorithm

    With the intention of improving the speed and accuracy of current breast cancer screening techniques, a novel method for automatically extracting and rendering a 3D representation of a potentially cancerous tumor, from 2D ultrasonic images, has been developed. Using fuzzy reasoning and the marching cubes algorithm, the system produce an interactive 3D image of the tumor. Using measurements and characteristics of the tumour's shape, a probability of malignancy is calculated. In tests, the results produced by the system are in excellent agreement with the doctors' diagnoses. (author)

  10. Engineering a 3D microfluidic culture platform for tumor-treating field application.

    Pavesi, Andrea; Adriani, Giulia; Tay, Andy; Warkiani, Majid Ebrahimi; Yeap, Wei Hseun; Wong, Siew Cheng; Kamm, Roger D

    2016-01-01

    The limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field; however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured individually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo-like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy. PMID:27215466

  11. Engineering a 3D microfluidic culture platform for tumor-treating field application

    Pavesi, Andrea; Adriani, Giulia; Tay, Andy; Warkiani, Majid Ebrahimi; Yeap, Wei Hseun; Wong, Siew Cheng; Kamm, Roger D.

    2016-05-01

    The limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field; however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured individually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo-like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy.

  12. Engineering a 3D microfluidic culture platform for tumor-treating field application

    Pavesi, Andrea; Adriani, Giulia; Tay, Andy; Warkiani, Majid Ebrahimi; Yeap, Wei Hseun; Wong, Siew Cheng; Kamm, Roger D.

    2016-01-01

    The limitations of current cancer therapies highlight the urgent need for a more effective therapeutic strategy. One promising approach uses an alternating electric field; however, the mechanisms involved in the disruption of the cancer cell cycle as well as the potential adverse effects on non-cancerous cells must be clarified. In this study, we present a novel microfluidic device with embedded electrodes that enables the application of an alternating electric field therapy to cancer cells in a 3D extracellular matrix. To demonstrate the potential of our system to aid in designing and testing new therapeutic approaches, cancer cells and cancer cell aggregates were cultured individually or co-cultured with endothelial cells. The metastatic potential of the cancer cells was reduced after electric field treatment. Moreover, the proliferation rate of the treated cancer cells was lower compared with that of the untreated cells, whereas the morphologies and proliferative capacities of the endothelial cells were not significantly affected. These results demonstrate that our novel system can be used to rapidly screen the effect of an alternating electric field on cancer and normal cells within an in vivo-like microenvironment with the potential to optimize treatment protocols and evaluate synergies between tumor-treating field treatment and chemotherapy. PMID:27215466

  13. 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions

    Wenzel, Carsten; Riefke, Björn; Gründemann, Stephan; Krebs, Alice; Christian, Sven; Prinz, Florian; Osterland, Marc; Golfier, Sven; Räse, Sebastian [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany); Ansari, Nariman [Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt (Germany); Esner, Milan; Bickle, Marc [Max Planck Institute of Molecular Cell Biology and Genetics, High-Throughput Technology Development Studio (TDS), Dresden (Germany); Pampaloni, Francesco; Mattheyer, Christian; Stelzer, Ernst H. [Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt (Germany); Parczyk, Karsten; Prechtl, Stefan [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany); Steigemann, Patrick, E-mail: Patrick.Steigemann@bayer.com [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany)

    2014-04-15

    Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions. - Highlights: • Establishment of a novel method for 3D cell culture based high-content screening. • First reported high

  14. 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions

    Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions. - Highlights: • Establishment of a novel method for 3D cell culture based high-content screening. • First reported high

  15. Assessment of different 3D culture systems to study tumor phenotype and chemosensitivity in pancreatic ductal adenocarcinoma.

    Zeeberg, Katrine; Cardone, Rosa Angela; Greco, Maria Raffaella; Saccomano, Mara; Nøhr-Nielsen, Asbjørn; Alves, Frauke; Pedersen, Stine Falsig; Reshkin, Stephan Joel

    2016-07-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease with a very poor prognosis, due to the influence of the tumor stroma, which promotes tumor growth, early invasion and chemoradiation resistance. Efforts to develop models for identifying novel anticancer therapeutic compounds have been hampered by the limited ability of in vitro models to mimic these in vivo tumor-stroma interactions. This has led to the development of various three-dimensional (3D) culture platforms recapitulating the in vivo tumor-stroma crosstalk and designed to better understand basic cancer processes and screen drug action. However, a consensus for different experimental 3D platforms is still missing in PDAC. We compared four PDAC cell lines of different malignancy grown in 2D monolayers to three of the more commonly used 3D techniques (ultralow adhesion concave microwells, Matrigel inclusion and organotypic systems) and to tumors derived from their orthotopic implantation in mice. In these 3D platforms, we observed that cells grow with very different tumor morphologies and the organotypic setting most closely resembles the tumor cytoarchitecture obtained by orthotopically implanting the four cell lines in mice. We then analyzed the molecular and cellular responses of one of these cell lines to epidermal growth factor receptor (EGFR) stimulation with EGF and inhibition with erlotinib and found that only in the 3D platforms, and especially the organotypic, cells: i) responded to EGF by changing the expression of signalling components underlying cell-stroma crosstalk and tissue architecture, growth, invasion and drug resistance (E-cadherin, EGFR, ezrin, β1 integrin, NHERF1 and HIF-1α) similar to those reported in vivo; ii) had stimulated growth and increased erlotinib sensitivity in response to EGF, more faithfully mimicking their known in vivo behaviour. Altogether, these results, indicate the organotypic as the most relevant physiological 3D system to study the

  16. A Bayesian approach to real-time 3D tumor localization via monoscopic x-ray imaging during treatment delivery

    Purpose: Monoscopic x-ray imaging with on-board kV devices is an attractive approach for real-time image guidance in modern radiation therapy such as VMAT or IMRT, but it falls short in providing reliable information along the direction of imaging x-ray. By effectively taking consideration of projection data at prior times and/or angles through a Bayesian formalism, the authors develop an algorithm for real-time and full 3D tumor localization with a single x-ray imager during treatment delivery. Methods: First, a prior probability density function is constructed using the 2D tumor locations on the projection images acquired during patient setup. Whenever an x-ray image is acquired during the treatment delivery, the corresponding 2D tumor location on the imager is used to update the likelihood function. The unresolved third dimension is obtained by maximizing the posterior probability distribution. The algorithm can also be used in a retrospective fashion when all the projection images during the treatment delivery are used for 3D localization purposes. The algorithm does not involve complex optimization of any model parameter and therefore can be used in a ''plug-and-play'' fashion. The authors validated the algorithm using (1) simulated 3D linear and elliptic motion and (2) 3D tumor motion trajectories of a lung and a pancreas patient reproduced by a physical phantom. Continuous kV images were acquired over a full gantry rotation with the Varian TrueBeam on-board imaging system. Three scenarios were considered: fluoroscopic setup, cone beam CT setup, and retrospective analysis. Results: For the simulation study, the RMS 3D localization error is 1.2 and 2.4 mm for the linear and elliptic motions, respectively. For the phantom experiments, the 3D localization error is < 1 mm on average and < 1.5 mm at 95th percentile in the lung and pancreas cases for all three scenarios. The difference in 3D localization error for different scenarios is small and is not

  17. Generation of a tumor spheroid in a microgravity environment as a 3D model of melanoma

    Marrero, Bernadette; Messina, Jane L.; Heller, Richard

    2009-01-01

    An in vitro 3D model was developed utilizing a synthetic microgravity environment to facilitate studying the cell interactions. 2D monolayer cell culture models have been successfully used to understand various cellular reactions that occur in vivo. There are some limitations to the 2D model that are apparent when compared to cells grown in a 3D matrix. For example, some proteins that are not expressed in a 2D model are found up-regulated in the 3D matrix. In this paper, we discuss techniques...

  18. AlgiMatrix™ Based 3D Cell Culture System as an In-Vitro Tumor Model for Anticancer Studies

    Godugu, Chandraiah; Patel, Apurva R.; Desai, Utkarsh; Andey, Terrick; Sams, Alexandria; Singh, Mandip

    2013-01-01

    Background Three-dimensional (3D) in-vitro cultures are recognized for recapitulating the physiological microenvironment and exhibiting high concordance with in-vivo conditions. Taking the advantages of 3D culture, we have developed the in-vitro tumor model for anticancer drug screening. Methods Cancer cells grown in 6 and 96 well AlgiMatrix™ scaffolds resulted in the formation of multicellular spheroids in the size range of 100–300 µm. Spheroids were grown in two weeks in cultures without co...

  19. 3D-CT imaging processing for qualitative and quantitative analysis of maxillofacial cysts and tumors Processamento de imagens em 3D-TC para análise qualitativa e quantitativa de cistos e tumores maxilo-faciais

    Marcelo de Gusmão Paraiso Cavalcanti

    2002-09-01

    Full Text Available The objective of this study was to evaluate spiral-computed tomography (3D-CT images of 20 patients presenting with cysts and tumors in the maxillofacial complex, in order to compare the surface and volume techniques of image rendering. The qualitative and quantitative appraisal indicated that the volume technique allowed a more precise and accurate observation than the surface method. On the average, the measurements obtained by means of the 3D volume-rendering technique were 6.28% higher than those obtained by means of the surface method. The sensitivity of the 3D surface technique was lower than that of the 3D volume technique for all conditions stipulated in the diagnosis and evaluation of lesions. We concluded that the 3D-CT volume rendering technique was more reproducible and sensitive than the 3D-CT surface method, in the diagnosis, treatment planning and evaluation of maxillofacial lesions, especially those with intra-osseous involvement.O presente trabalho consiste em um estudo associativo e comparativo entre as técnicas de superfície e volume para a reconstrução de imagens em três dimensões (3D utilizando tomografia computadorizada (TC. Foram realizadas tomografias computadorizadas em espiral de 20 pacientes com cistos e tumores do complexo maxilo-facial para análise qualitativa e quantitativa, utilizando métodos de superfície e de volume em 3D. A comparação interexaminadores apresentou erro padrão percentual menos elevado para a técnica de volume (1,94% que para a técnica de superfície (4,38%, indicando a maior reprodutibilidade do primeiro método. As medidas obtidas pela técnica de volume foram em média 6,28% mais elevadas que as medidas obtidas pela técnica de superfície. A técnica de volume apresentou sensibilidade mais elevada que a técnica de superfície na identificação das lesões do complexo maxilo-facial. A técnica de volume em 3D-TC, utilizando a metodologia da computação gráfica, apresentou maior

  20. Intrinsic subtypes and tumor grades in breast cancer are associated with distinct 3-D power Doppler sonographic vascular features

    Chang, Yeun-Chung [Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10041, Taiwan, ROC (China); Huang, Yao-Sian [Department of Computer Science and Information Engineering, National Taiwan University, Taipei 10617, Taiwan, ROC (China); Huang, Chiun-Sheng [Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10041, Taiwan, ROC (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan, ROC (China); Chen, Jeon-Hor [Center for Functional Onco-Imaging and Department of Radiological Science, University of California Irvine, California, CA 92868 (United States); Department of Radiology, E-Da Hospital and I-Shou University, Kaohsiung 82445, Taiwan, ROC (China); Chang, Ruey-Feng, E-mail: rfchang@csie.ntu.edu.tw [Department of Computer Science and Information Engineering, National Taiwan University, Taipei 10617, Taiwan, ROC (China); Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan, ROC (China)

    2014-08-15

    Purpose: This study aimed to investigate the three-dimensional (3-D) power Doppler ultrasonographic (PDUS) vascular features of breast carcinoma according to intrinsic subtypes, nodal stage, and tumor grade. Materials and methods: Total 115 receiving mastectomy breast carcinomas (mean size, 2.5 cm; range, 0.7–6.5 cm), including 102 invasive ductal carcinomas (IDC), 10 ductal carcinomas in situ (DCIS), and 3 invasive lobular carcinomas (ILC) diagnosed after mastectomy, were used in this retrospective study. Sixty IDC had nodal status and histopathologic tumor grades available for analysis. Vascular features, including number of vascular trees (NV), longest path length (LPL), total vessel length (TVL), number of bifurcations (NB), distance metric (DM), inflection count metric (ICM), vessel diameter (VD), and vessel-to-volume ratio (VVR) were extracted using 3-D thinning method. The Mann–Whitney U test, Student's t-test, one-way ANOVA, and Kruskal–Wallis test were performed as appropriate. Results: There was no significant difference of vascular features among IDC, DCIS and ILC. Except VD, vascular features in luminal type were significantly lower compared to HER2-enriched or triple negative types (p < 0.05). Compared to ER+ (estrogen receptor positive) tumors, all features in ER− (estrogen receptor negative) tumors were significantly higher (p < 0.01). Despite some significantly higher vascular features in high grade IDC compared to low and intermediate grade, there was no significant correlation between vascular features and nodal stages. Conclusion: Differences in 3-D PDUS vascular features among intrinsic types of IDC are attributed to their ER status. Vascular features extracted by 3-D PDUS correlate with tumor grades but not nodal stage in IDC.

  1. AlgiMatrix™ based 3D cell culture system as an in-vitro tumor model for anticancer studies.

    Chandraiah Godugu

    Full Text Available BACKGROUND: Three-dimensional (3D in-vitro cultures are recognized for recapitulating the physiological microenvironment and exhibiting high concordance with in-vivo conditions. Taking the advantages of 3D culture, we have developed the in-vitro tumor model for anticancer drug screening. METHODS: Cancer cells grown in 6 and 96 well AlgiMatrix™ scaffolds resulted in the formation of multicellular spheroids in the size range of 100-300 µm. Spheroids were grown in two weeks in cultures without compromising the growth characteristics. Different marketed anticancer drugs were screened by incubating them for 24 h at 7, 9 and 11 days in 3D cultures and cytotoxicity was measured by AlamarBlue® assay. Effectiveness of anticancer drug treatments were measured based on spheroid number and size distribution. Evaluation of apoptotic and anti-apoptotic markers was done by immunohistochemistry and RT-PCR. The 3D results were compared with the conventional 2D monolayer cultures. Cellular uptake studies for drug (Doxorubicin and nanoparticle (NLC were done using spheroids. RESULTS: IC(50 values for anticancer drugs were significantly higher in AlgiMatrix™ systems compared to 2D culture models. The cleaved caspase-3 expression was significantly decreased (2.09 and 2.47 folds respectively for 5-Fluorouracil and Camptothecin in H460 spheroid cultures compared to 2D culture system. The cytotoxicity, spheroid size distribution, immunohistochemistry, RT-PCR and nanoparticle penetration data suggested that in vitro tumor models show higher resistance to anticancer drugs and supporting the fact that 3D culture is a better model for the cytotoxic evaluation of anticancer drugs in vitro. CONCLUSION: The results from our studies are useful to develop a high throughput in vitro tumor model to study the effect of various anticancer agents and various molecular pathways affected by the anticancer drugs and formulations.

  2. Longitudinal, label-free, quantitative tracking of cell death and viability in a 3D tumor model with OCT

    Jung, Yookyung; Klein, Oliver J.; Wang, Hequn; Evans, Conor L.

    2016-06-01

    Three-dimensional in vitro tumor models are highly useful tools for studying tumor growth and treatment response of malignancies such as ovarian cancer. Existing viability and treatment assessment assays, however, face shortcomings when applied to these large, complex, and heterogeneous culture systems. Optical coherence tomography (OCT) is a noninvasive, label-free, optical imaging technique that can visualize live cells and tissues over time with subcellular resolution and millimeters of optical penetration depth. Here, we show that OCT is capable of carrying out high-content, longitudinal assays of 3D culture treatment response. We demonstrate the usage and capability of OCT for the dynamic monitoring of individual and combination therapeutic regimens in vitro, including both chemotherapy drugs and photodynamic therapy (PDT) for ovarian cancer. OCT was validated against the standard LIVE/DEAD Viability/Cytotoxicity Assay in small tumor spheroid cultures, showing excellent correlation with existing standards. Importantly, OCT was shown to be capable of evaluating 3D spheroid treatment response even when traditional viability assays failed. OCT 3D viability imaging revealed synergy between PDT and the standard-of-care chemotherapeutic carboplatin that evolved over time. We believe the efficacy and accuracy of OCT in vitro drug screening will greatly contribute to the field of cancer treatment and therapy evaluation.

  3. A computational model for estimating tumor margins in complementary tactile and 3D ultrasound images

    Shamsil, Arefin; Escoto, Abelardo; Naish, Michael D.; Patel, Rajni V.

    2016-03-01

    Conventional surgical methods are effective for treating lung tumors; however, they impose high trauma and pain to patients. Minimally invasive surgery is a safer alternative as smaller incisions are required to reach the lung; however, it is challenging due to inadequate intraoperative tumor localization. To address this issue, a mechatronic palpation device was developed that incorporates tactile and ultrasound sensors capable of acquiring surface and cross-sectional images of palpated tissue. Initial work focused on tactile image segmentation and fusion of position-tracked tactile images, resulting in a reconstruction of the palpated surface to compute the spatial locations of underlying tumors. This paper presents a computational model capable of analyzing orthogonally-paired tactile and ultrasound images to compute the surface circumference and depth margins of a tumor. The framework also integrates an error compensation technique and an algebraic model to align all of the image pairs and to estimate the tumor depths within the tracked thickness of a palpated tissue. For validation, an ex vivo experimental study was conducted involving the complete palpation of 11 porcine liver tissues injected with iodine-agar tumors of varying sizes and shapes. The resulting tactile and ultrasound images were then processed using the proposed model to compute the tumor margins and compare them to fluoroscopy based physical measurements. The results show a good negative correlation (r = -0.783, p = 0.004) between the tumor surface margins and a good positive correlation (r = 0.743, p = 0.009) between the tumor depth margins.

  4. A comparison of 3D-CTA and 4D-CE-MRA for the dynamic monitoring of angiogenesis in a rabbit VX2 tumor

    Purpose: To compare three-dimensional computed tomography angiography (3D-CTA) and four-dimensional contrast-enhanced magnetic resonance angiography (4D-CE-MRA) for the in vivo monitoring of tumor angiogenesis. Materials and methods: VX2 tumors were implanted into the right thigh muscle of 30 New Zealand white rabbits. The animals were randomly assigned to 5 groups, which, respectively, were scanned by 3D-CTA and 4D-CE-MRA on day 4, 7, 10, 13, or 16 after tumor implantation. After scanning, tumors were resected and processed for conventional histology and CD-31 immunohistochemistry. Tumor volume measurements derived from CT and MR imaging were compared with histopathological data. The minimum tumor diameter and the number of new tumor blood vessels detectable by 3D-CTA and 4D-CE-MRA were also compared. Results: There were no significant differences in the tumor volume measurements derived from CT, MR, and histological analysis. The minimum diameter of tumor vessels detectable by 3D-CTA (0.68 ± 0.07 mm) was significantly less than that by 4D-CE-MRA (0.85 ± 0.12 mm) (P = 0.005). The number of tumor vessels detected by each imaging method was not significantly different until day 13 after implantation, when 3D-CTA detected a greater number (P < 0.001). The morphologic process of tumor angiogenesis was demonstrated dynamically by 3D-CTA and 4D-CE-MRA in vivo. Conclusions: Tumor angiogenesis can be dynamically monitored in vivo by 3D-CTA and 4D-CE-MRA. Of the two methods, 3D-CTA has better spatial resolution, but 4D-CE-MRA allows temporal resolution of tumor angiogenesis.

  5. 3D modeling of human cancer: A PEG-fibrin hydrogel system to study the role of tumor microenvironment and recapitulate the in vivo effect of oncolytic adenovirus.

    Del Bufalo, Francesca; Manzo, Teresa; Hoyos, Valentina; Yagyu, Shigeki; Caruana, Ignazio; Jacot, Jeffrey; Benavides, Omar; Rosen, Daniel; Brenner, Malcolm K

    2016-04-01

    Interactions between malignant and stromal cells and the 3D spatial architecture of the tumor both substantially modify tumor behavior, including the responses to small molecule drugs and biological therapies. Conventional 2D culture systems cannot replicate this complexity. To overcome these limitations and more accurately model solid tumors, we developed a highly versatile 3D PEG-fibrin hydrogel model of human lung adenocarcinoma. Our model relevantly recapitulates the effect of oncolytic adenovirus; tumor responses in this setting nearly reproduce those observed in vivo. We have also validated the use of this model for complex, long-term, 3D cultures of cancer cells and their stroma (fibroblasts and endothelial cells). Both tumor proliferation and invasiveness were enhanced in the presence of stromal components. These results validate our 3D hydrogel model as a relevant platform to study cancer biology and tumor responses to biological treatments. PMID:26826297

  6. Extracellular matrix composition and rigidity regulate invasive behavior and response to PDT in 3D pancreatic tumor models

    Cramer, Gwendolyn; El-Hamidi, Hamid; Jafari, Seyedehrojin; Jones, Dustin P.; Celli, Jonathan P.

    2016-03-01

    The composition and mechanical compliance of the extracellular matrix (ECM) have been shown to serve as regulators of tumor growth and invasive behavior. These effects may be particularly relevant in tumors of the pancreas, noted for a profound desmoplastic reaction and an abundance of stroma rich in ECM. In view of recent progress in the clinical implementation of photodynamic therapy (PDT) for pancreatic tumors, in this report we examine how ECM composition and rheological properties impact upon invasive behavior and response to PDT in 3D multicellular pancreatic tumor spheroids in ECM environments with characterized rheological properties. Tumor spheroids were cultured initially in attachment-free conditions to form millimeter-sized spheroids that were transplanted into reconstituted ECM microenvironments (Matrigel and Type I Collagen) that were characterized using bulk oscillatory shear rheology. Analysis of growth behavior shows that the soft collagen ECM promoted growth and extensive invasion and this microenvironment was used in subsequent assessment of PDT and chemotherapy response. Evaluation of treatment response revealed that primary tumor nodule growth is inhibited more effectively with PDT, while verteporfin PDT response is significantly enhanced in the ECM-infiltrating populations that are non-responsive to oxaliplatin chemotherapy. This finding is potentially significant, suggesting the potential for PDT to target these clinically problematic invasive populations that are associated with aggressive metastatic progression and chemoresistance. Experiments to further validate and identify the mechanistic basis of this observation are ongoing.

  7. APPLICATION OF 3D MODELING IN 3D PRINTING FOR THE LOWER JAW RECONSTRUCTION

    Yu. Yu. Dikov

    2015-01-01

    Full Text Available Aim of study: improvement of functional and aesthetic results of microsurgery reconstructions of the lower jaw due to the use of the methodology of 3D modeling and 3D printing. Application of this methodology has been demonstrated on the example of treatment of 4 patients with locally distributed tumors of the mouth cavity, who underwent excision of the tumor with simultaneous reconstruction of the lower jaw with revascularized fibular graft.Before, one patient has already undergo segmental resection of the lower jaw with the defect replacement with the avascular ileac graft and a reconstruction plate. Then, a relapse of the disease and lysis of the graft has developed with him. Modeling of the graft according to the shape of the lower jaw was performed by making osteotomies of the bone part of the graft using three-dimensional virtual models created by computed tomography data. Then these 3D models were printed with a 3D printer of plastic with the scale of 1:1 with the fused deposition modeling (FDM technology and were used during the surgery in the course of modeling of the graft. Sterilizing of the plastic model was performed in the formalin chamber.This methodology allowed more specific reconstruction of the resected fragment of the lower jaw and get better functional and aesthetic results and prepare patients to further dental rehabilitation. Advantages of this methodology are the possibility of simultaneous performance of stages of reconstruction and resection and shortening of the time of surgery.

  8. Treating benign optic nerve tumors with a 3-D conformal plan

    A 68 year old male patient presented for radiation therapy for treatment of a benign tumor, a glioma of his left optic nerve. The radiation oncologist intended to prescribe 52.2 Gy to the planning target volume, while maintaining a maximum of 54 Gy to the optic nerves and the optic chiasm and a maximum of 40–45 Gy to the globes in order to minimize the possibility of damaging the optic system, which is especially important as this is a benign tumor. The dosimetrist devised a conformal non-coplanar three-dimensional plan with a slightly weighted forward planning component. This plan was created in approximately 15 minutes after the critical organs and the targets were delineated and resulted in an extremely conformal and homogenous plan, treating the target while sparing the nearby critical structures. This approach can also be extended to other tumors in the brain - benign or malignant

  9. Azo-Based Iridium(III) Complexes as Multicolor Phosphorescent Probes to Detect Hypoxia in 3D Multicellular Tumor Spheroids

    Sun, Lingli; Li, Guanying; Chen, Xiang; Chen, Yu; Jin, Chengzhi; Ji, Liangnian; Chao, Hui

    2015-10-01

    Hypoxia is an important characteristic of malignant solid tumors and is considered as a possible causative factor for serious resistance to chemo- and radiotherapy. The exploration of novel fluorescent probes capable of detecting hypoxia in solid tumors will aid tumor diagnosis and treatment. In this study, we reported the design and synthesis of a series of “off-on” phosphorescence probes for hypoxia detection in adherent and three-dimensional multicellular spheroid models. All of the iridium(III) complexes incorporate an azo group as an azo-reductase reactive moiety to detect hypoxia. Reduction of non-phosphorescent probes Ir1-Ir8 by reductases under hypoxic conditions resulted in the generation of highly phosphorescent corresponding amines for detection of hypoxic regions. Moreover, these probes can penetrate into 3D multicellular spheroids over 100 μm and image the hypoxic regions. Most importantly, these probes display a high selectivity for the detection of hypoxia in 2D cells and 3D multicellular spheroids.

  10. Estimation of Pulmonary Motion in Healthy Subjects and Patients with Intrathoracic Tumors Using 3D-Dynamic MRI: Initial Results

    Plathow, Christian; Schoebinger, Max; Meinzer, Heinz Peter [German Cancer Research Center, Heidelberg (Germany); Herth, Felix; Tuengerthal, Siegfried [Clinic of Thoracic Disease, Heidelberg (Germany); Kauczor, Hans Ulrich [University of Heidelberg, Heidelberg (Germany)

    2009-12-15

    To estimate a new technique for quantifying regional lung motion using 3D-MRI in healthy volunteers and to apply the technique in patients with intra- or extrapulmonary tumors. Intraparenchymal lung motion during a whole breathing cycle was quantified in 30 healthy volunteers using 3D-dynamic MRI (FLASH [fast low angle shot] 3D, TRICKS [time-resolved interpolated contrast kinetics]). Qualitative and quantitative vector color maps and cumulative histograms were performed using an introduced semiautomatic algorithm. An analysis of lung motion was performed and correlated with an established 2D-MRI technique for verification. As a proof of concept, the technique was applied in five patients with non-small cell lung cancer (NSCLC) and 5 patients with malignant pleural mesothelioma (MPM). The correlation between intraparenchymal lung motion of the basal lung parts and the 2D-MRI technique was significant (r = 0.89, p < 0.05). Also, the vector color maps quantitatively illustrated regional lung motion in all healthy volunteers. No differences were observed between both hemithoraces, which was verified by cumulative histograms. The patients with NSCLC showed a local lack of lung motion in the area of the tumor. In the patients with MPM, there was global diminished motion of the tumor bearing hemithorax, which improved significantly after chemotherapy (CHT) (assessed by the 2D- and 3D-techniques) (p < 0.01). Using global spirometry, an improvement could also be shown (vital capacity 2.9 {+-} 0.5 versus 3.4 L {+-} 0.6, FEV1 0.9 {+-} 0.2 versus 1.4 {+-} 0.2 L) after CHT, but this improvement was not significant. A 3D-dynamic MRI is able to quantify intraparenchymal lung motion. Local and global parenchymal pathologies can be precisely located and might be a new tool used to quantify even slight changes in lung motion (e.g. in therapy monitoring, follow-up studies or even benign lung diseases)

  11. Estimation of Pulmonary Motion in Healthy Subjects and Patients with Intrathoracic Tumors Using 3D-Dynamic MRI: Initial Results

    To estimate a new technique for quantifying regional lung motion using 3D-MRI in healthy volunteers and to apply the technique in patients with intra- or extrapulmonary tumors. Intraparenchymal lung motion during a whole breathing cycle was quantified in 30 healthy volunteers using 3D-dynamic MRI (FLASH [fast low angle shot] 3D, TRICKS [time-resolved interpolated contrast kinetics]). Qualitative and quantitative vector color maps and cumulative histograms were performed using an introduced semiautomatic algorithm. An analysis of lung motion was performed and correlated with an established 2D-MRI technique for verification. As a proof of concept, the technique was applied in five patients with non-small cell lung cancer (NSCLC) and 5 patients with malignant pleural mesothelioma (MPM). The correlation between intraparenchymal lung motion of the basal lung parts and the 2D-MRI technique was significant (r = 0.89, p < 0.05). Also, the vector color maps quantitatively illustrated regional lung motion in all healthy volunteers. No differences were observed between both hemithoraces, which was verified by cumulative histograms. The patients with NSCLC showed a local lack of lung motion in the area of the tumor. In the patients with MPM, there was global diminished motion of the tumor bearing hemithorax, which improved significantly after chemotherapy (CHT) (assessed by the 2D- and 3D-techniques) (p < 0.01). Using global spirometry, an improvement could also be shown (vital capacity 2.9 ± 0.5 versus 3.4 L ± 0.6, FEV1 0.9 ± 0.2 versus 1.4 ± 0.2 L) after CHT, but this improvement was not significant. A 3D-dynamic MRI is able to quantify intraparenchymal lung motion. Local and global parenchymal pathologies can be precisely located and might be a new tool used to quantify even slight changes in lung motion (e.g. in therapy monitoring, follow-up studies or even benign lung diseases)

  12. Mechanically assisted 3D ultrasound for pre-operative assessment and guiding percutaneous treatment of focal liver tumors

    Sadeghi Neshat, Hamid; Bax, Jeffery; Barker, Kevin; Gardi, Lori; Chedalavada, Jason; Kakani, Nirmal; Fenster, Aaron

    2014-03-01

    Image-guided percutaneous ablation is the standard treatment for focal liver tumors deemed inoperable and is commonly used to maintain eligibility for patients on transplant waitlists. Radiofrequency (RFA), microwave (MWA) and cryoablation technologies are all delivered via one or a number of needle-shaped probes inserted directly into the tumor. Planning is mostly based on contrast CT/MRI. While intra-procedural CT is commonly used to confirm the intended probe placement, 2D ultrasound (US) remains the main, and in some centers the only imaging modality used for needle guidance. Corresponding intraoperative 2D US with planning and other intra-procedural imaging modalities is essential for accurate needle placement. However, identification of matching features of interest among these images is often challenging given the limited field-of-view (FOV) and low quality of 2D US images. We have developed a passive tracking arm with a motorized scan-head and software tools to improve guiding capabilities of conventional US by large FOV 3D US scans that provides more anatomical landmarks that can facilitate registration of US with both planning and intra-procedural images. The tracker arm is used to scan the whole liver with a high geometrical accuracy that facilitates multi-modality landmark based image registration. Software tools are provided to assist with the segmentation of the ablation probes and tumors, find the 2D view that best shows the probe(s) from a 3D US image, and to identify the corresponding image from planning CT scans. In this paper, evaluation results from laboratory testing and a phase 1 clinical trial for planning and guiding RFA and MWA procedures using the developed system will be presented. Early clinical results show a comparable performance to intra-procedural CT that suggests 3D US as a cost-effective alternative with no side-effects in centers where CT is not available.

  13. Cranial nerve assessment in cavernous sinus tumors with contrast-enhanced 3D fast-imaging employing steady-state acquisition MR imaging

    Amemiya, Shiori; Aoki, Shigeki; Ohtomo, Kuni [University of Tokyo, Department of Radiology, Graduate School of Medicine, Bunkyo-ku, Tokyo (Japan)

    2009-07-15

    The purpose of this study is to apply contrast-enhanced 3D fast-imaging employing steady-state acquisition (3D-FIESTA) imaging to the evaluation of cranial nerves (CN) in patients with cavernous sinus tumors. Contrast-enhanced 3D-FIESTA images were acquired from ten patients with cavernous sinus tumors with a 3-T unit. In all cases, the trigeminal nerve with tumor involvement was easily identified in the cavernous portions. Although oculomotor and abducens nerves were clearly visualized against the tumor area with intense contrast enhancement, they were hardly identifiable within the area lacking contrast enhancement. The trochlear nerve was visualized in part, but not delineated as a linear structure outside of the lesion. Contrast-enhanced 3D-FIESTA can be useful in the assessment of cranial nerves in and around the cavernous sinus with tumor involvement. (orig.)

  14. Cranial nerve assessment in cavernous sinus tumors with contrast-enhanced 3D fast-imaging employing steady-state acquisition MR imaging

    The purpose of this study is to apply contrast-enhanced 3D fast-imaging employing steady-state acquisition (3D-FIESTA) imaging to the evaluation of cranial nerves (CN) in patients with cavernous sinus tumors. Contrast-enhanced 3D-FIESTA images were acquired from ten patients with cavernous sinus tumors with a 3-T unit. In all cases, the trigeminal nerve with tumor involvement was easily identified in the cavernous portions. Although oculomotor and abducens nerves were clearly visualized against the tumor area with intense contrast enhancement, they were hardly identifiable within the area lacking contrast enhancement. The trochlear nerve was visualized in part, but not delineated as a linear structure outside of the lesion. Contrast-enhanced 3D-FIESTA can be useful in the assessment of cranial nerves in and around the cavernous sinus with tumor involvement. (orig.)

  15. Correlating intravital multi-photon microscopy to 3D electron microscopy of invading tumor cells using anatomical reference points.

    Matthia A Karreman

    Full Text Available Correlative microscopy combines the advantages of both light and electron microscopy to enable imaging of rare and transient events at high resolution. Performing correlative microscopy in complex and bulky samples such as an entire living organism is a time-consuming and error-prone task. Here, we investigate correlative methods that rely on the use of artificial and endogenous structural features of the sample as reference points for correlating intravital fluorescence microscopy and electron microscopy. To investigate tumor cell behavior in vivo with ultrastructural accuracy, a reliable approach is needed to retrieve single tumor cells imaged deep within the tissue. For this purpose, fluorescently labeled tumor cells were subcutaneously injected into a mouse ear and imaged using two-photon-excitation microscopy. Using near-infrared branding, the position of the imaged area within the sample was labeled at the skin level, allowing for its precise recollection. Following sample preparation for electron microscopy, concerted usage of the artificial branding and anatomical landmarks enables targeting and approaching the cells of interest while serial sectioning through the specimen. We describe here three procedures showing how three-dimensional (3D mapping of structural features in the tissue can be exploited to accurately correlate between the two imaging modalities, without having to rely on the use of artificially introduced markers of the region of interest. The methods employed here facilitate the link between intravital and nanoscale imaging of invasive tumor cells, enabling correlating function to structure in the study of tumor invasion and metastasis.

  16. Liver Tumor Segmentation from MR Images Using 3D Fast Marching Algorithm and Single Hidden Layer Feedforward Neural Network

    Trong-Ngoc Le

    2016-01-01

    Full Text Available Objective. Our objective is to develop a computerized scheme for liver tumor segmentation in MR images. Materials and Methods. Our proposed scheme consists of four main stages. Firstly, the region of interest (ROI image which contains the liver tumor region in the T1-weighted MR image series was extracted by using seed points. The noise in this ROI image was reduced and the boundaries were enhanced. A 3D fast marching algorithm was applied to generate the initial labeled regions which are considered as teacher regions. A single hidden layer feedforward neural network (SLFN, which was trained by a noniterative algorithm, was employed to classify the unlabeled voxels. Finally, the postprocessing stage was applied to extract and refine the liver tumor boundaries. The liver tumors determined by our scheme were compared with those manually traced by a radiologist, used as the “ground truth.” Results. The study was evaluated on two datasets of 25 tumors from 16 patients. The proposed scheme obtained the mean volumetric overlap error of 27.43% and the mean percentage volume error of 15.73%. The mean of the average surface distance, the root mean square surface distance, and the maximal surface distance were 0.58 mm, 1.20 mm, and 6.29 mm, respectively.

  17. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  18. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    Min Yugang; Santhanam, Anand; Ruddy, Bari H [University of Central Florida, FL (United States); Neelakkantan, Harini; Meeks, Sanford L [M D Anderson Cancer Center Orlando, FL (United States); Kupelian, Patrick A, E-mail: anand.santhanam@orlandohealth.co [Department of Radiation Oncology, University of California, Los Angeles, CA (United States)

    2010-09-07

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  19. A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

    Min, Yugang; Santhanam, Anand; Neelakkantan, Harini; Ruddy, Bari H.; Meeks, Sanford L.; Kupelian, Patrick A.

    2010-09-01

    In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

  20. Integration of 3D 1H-magnetic resonance spectroscopy data into neuronavigation systems for tumor biopsies

    Kanberoglu, Berkay; Moore, Nina Z.; Frakes, David; Karam, Lina J.; Debbins, Josef P.; Preul, Mark C.

    2013-03-01

    Many important applications in clinical medicine can benefit from the fusion of spectroscopy data with anatomical images. For example, the correlation of metabolite profiles with specific regions of interest in anatomical tumor images can be useful in characterizing and treating heterogeneous tumors that appear structurally homogeneous. Such applications can build on the correlation of data from in-vivo Proton Magnetic Resonance Spectroscopy Imaging (1HMRSI) with data from genetic and ex-vivo Nuclear Magnetic Resonance spectroscopy. To establish that correlation, tissue samples must be neurosurgically extracted from specifically identified locations with high accuracy. Toward that end, this paper presents new neuronavigation technology that enhances current clinical capabilities in the context of neurosurgical planning and execution. The proposed methods improve upon the current state-of-the-art in neuronavigation through the use of detailed three dimensional (3D) 1H-MRSI data. MRSI spectra are processed and analyzed, and specific voxels are selected based on their chemical contents. 3D neuronavigation overlays are then generated and applied to anatomical image data in the operating room. Without such technology, neurosurgeons must rely on memory and other qualitative resources alone for guidance in accessing specific MRSI-identified voxels. In contrast, MRSI-based overlays provide quantitative visual cues and location information during neurosurgery. The proposed methods enable a progressive new form of online MRSI-guided neuronavigation that we demonstrate in this study through phantom validation and clinical application.

  1. Topographical guidance of 3D tumor cell migration at an interface of collagen densities

    During cancer progression, metastatic cells leave the primary tumor and invade into the fibrous extracellular matrix (ECM) within the surrounding stroma. This ECM network is highly heterogeneous, and interest in understanding how this network can affect cell behavior has increased in the past several decades. However, replicating this heterogeneity has proven challenging. Here, we designed and utilized a method to create a well-defined interface between two distinct regions of high- and low-density collagen gels to mimic the heterogeneities in density found in the tumor stroma. We show that cells will invade preferentially from the high-density side into the low-density side. We also demonstrate that the net cell migration is a function of the density of the collagen in which the cells are embedded, and the difference in density between the two regions has minimal effect on cell net displacement and distance travelled. Our data further indicate that a low-to-high density interface promotes directional migration and induces formation of focal adhesion on the interface surface. Together, the current results demonstrate how ECM heterogeneities, in the form of interfacial boundaries, can affect cell migration. (paper)

  2. Designing PDT-based combinations to overcome chemoresistance in heterocellular 3D tumor models (Conference Presentation)

    Rizvi, Imran; Briars, Emma A.; Bulin, Anne-Laure; Anbil, Sriram; Vecchio, Daniela; Alkhateeb, Ahmed; Hanna, William R.; Celli, Jonathan P.; Hasan, Tayyaba

    2016-03-01

    A major barrier to treating advanced-stage cancers is heterogeneity in the responsiveness of metastatic disease to conventional therapies leading to resistance and treatment failure. Photodynamic therapy (PDT) has been shown to synergize with conventional agents and to overcome the evasion pathways that cause resistance. Developing PDT-based combinations that target resistant tumor populations and cooperate mechanistically with conventional agents is an increasingly promising approach to improve therapeutic efficacy while minimizing toxicity, particularly in complex disease sites. Identifying the molecular, cellular, and microenvironmental cues that lead to heterogeneity and treatment resistance is critical to developing strategies to target unresponsive regions of stubborn disease. Cell-based research platforms that integrate key microenvironmental cues are emerging as increasingly important tools to improve the translational efficiency of new agents, and to design combination regimens. Among the challenges associated with developing and scaling complex cell-based screening platforms is the need to integrate, and balance, biological relevance with appropriate, high-content imaging routines that provide meaningful quantitative readouts of therapeutic response. The benefits and challenges associated with deriving meaningful insights from complex cell-based models will be presented, with a particular emphasis on overcoming chemoresistance mediated by physical stress and communication with stromal partners (e.g. tumor endothelial cells, which are emerging as dynamic regulators of treatment resistance) using PDT-based combinations.

  3. 3D-SPGR序列在脑肿瘤MRI中的应用%The Application of MRI 3D-SPGR Sequence in Brain Tumor

    李长青

    2000-01-01

    @@ 脑肿瘤是磁共振成像中较常见的肿瘤,当前应用于脑肿瘤的MR技术主要是二维的SE序列,笔者通过对41例患者行3D-SPGR序列扫描,试图评价该序列在脑肿瘤MRI的应用价值.

  4. Accuracy of a 3D online motion compensation system for tumor therapy with scanned ion beams

    An integrated three-dimensional online motion compensation (3DOMC) system is being developed at GSI to treat tumors in moving organs with scanned ion beams. Target motion is detected by a laser distance sensor, and the motion compensation parameters are calculated in a dedicated module of the treatment control system (TCS). The lateral compensation parameters are sent to the TCS controller of the scanning magnets to adapt the beam laterally. The longitudinal compensation parameters are sent to a range shifter which consists of two sets of PMMA wedges mounted on linear motors. The wedges are placed symmetrically to form a double wedge with a homogeneous thickness in the overlapped area. By moving the wedges apart or together with the linear motors the range of the traversing ion beams can be modulated. The system response time has been optimized to ∼1ms for lateral compensation and to ∼25 ms for 5 mm water equivalent depth compensation. In experiments with a position detector deviations of 0.3 mm RMS were measured for lateral motion compensation by comparing measured and nominal beam positions. For longitudinal compensation an accuracy of 0.2(2) mm was obtained by comparing stationary depth dose profiles to those with motion compensation

  5. Co-culture of 3D tumor spheroids with fibroblasts as a model for epithelial–mesenchymal transition in vitro

    Epithelial–mesenchymal transition (EMT) acts as a facilitator of metastatic dissemination in the invasive margin of malignant tumors where active tumor–stromal crosstalks take place. Co-cultures of cancer cells with cancer-associated fibroblasts (CAFs) are often used as in vitro models of EMT. We established a tumor–fibroblast proximity co-culture using HT-29 tumor spheroids (TSs) with CCD-18co fibroblasts. When co-cultured with TSs, CCD-18co appeared activated, and proliferative activity as well as cell migration increased. Expression of fibronectin increased whereas laminin and type I collagen decreased in TSs co-cultured with fibroblasts compared to TSs alone, closely resembling the margin of in vivo xenograft tissue. Active TGFβ1 in culture media significantly increased in TS co-cultures but not in 2D co-cultures of cancer cells–fibroblasts, indicating that 3D context-associated factors from TSs may be crucial to crosstalks between cancer cells and fibroblasts. We also observed in TSs co-cultured with fibroblasts increased expression of α-SMA, EGFR and CTGF; reduced expression of membranous β-catenin and E-cadherin, together suggesting an EMT-like changes similar to a marginal region of xenograft tissue in vivo. Overall, our in vitro TS–fibroblast proximity co-culture mimics the EMT-state of the invasive margin of in vivo tumors in early metastasis. - Highlights: • An adjacent co-culture of tumor spheroids and fibroblasts is presented as EMT model. • Activation of fibroblasts and increased cell migration were shown in co-culture. • Expression of EMT-related factors in co-culture was similar to that in tumor tissue. • Crosstalk between spheroids and fibroblasts was demonstrated by secretome analysis

  6. Co-culture of 3D tumor spheroids with fibroblasts as a model for epithelial–mesenchymal transition in vitro

    Kim, Sun-Ah, E-mail: j.sarah.k@gmail.com [Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Lee, Eun Kyung, E-mail: leeek@catholic.ac.kr [Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Kuh, Hyo-Jeong, E-mail: hkuh@catholic.ac.kr [Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of)

    2015-07-15

    Epithelial–mesenchymal transition (EMT) acts as a facilitator of metastatic dissemination in the invasive margin of malignant tumors where active tumor–stromal crosstalks take place. Co-cultures of cancer cells with cancer-associated fibroblasts (CAFs) are often used as in vitro models of EMT. We established a tumor–fibroblast proximity co-culture using HT-29 tumor spheroids (TSs) with CCD-18co fibroblasts. When co-cultured with TSs, CCD-18co appeared activated, and proliferative activity as well as cell migration increased. Expression of fibronectin increased whereas laminin and type I collagen decreased in TSs co-cultured with fibroblasts compared to TSs alone, closely resembling the margin of in vivo xenograft tissue. Active TGFβ1 in culture media significantly increased in TS co-cultures but not in 2D co-cultures of cancer cells–fibroblasts, indicating that 3D context-associated factors from TSs may be crucial to crosstalks between cancer cells and fibroblasts. We also observed in TSs co-cultured with fibroblasts increased expression of α-SMA, EGFR and CTGF; reduced expression of membranous β-catenin and E-cadherin, together suggesting an EMT-like changes similar to a marginal region of xenograft tissue in vivo. Overall, our in vitro TS–fibroblast proximity co-culture mimics the EMT-state of the invasive margin of in vivo tumors in early metastasis. - Highlights: • An adjacent co-culture of tumor spheroids and fibroblasts is presented as EMT model. • Activation of fibroblasts and increased cell migration were shown in co-culture. • Expression of EMT-related factors in co-culture was similar to that in tumor tissue. • Crosstalk between spheroids and fibroblasts was demonstrated by secretome analysis.

  7. Clinical evaluation of 3D/3D MRI-CBCT automatching on brain tumors for online patient setup verification - A step towards MRI-based treatment planning

    Buhl, S.K.; Duun-Christensen, Anne Katrine; Kristensen, B.H.;

    2010-01-01

    undergoing postoperative radiotherapy for malignant brain tumors received a weekly CBCT. In total 18 scans was matched with both CT and MRI as reference. The CBCT scans were acquired using a Clinac iX 2300 linear accelerator (Varian Medical Systems) with an On-Board Imager (OBI). Results. For the phantom...

  8. Dose distribution and tumor control probability in out-of-field lymph node stations in intensity modulated radiotherapy (IMRT) vs 3D-conformal radiotherapy (3D-CRT) of non-small-cell lung cancer: an in silico analysis

    The advent of IMRT and image-guided radiotherapy (IGRT) in combination with involved-field radiotherapy (IF-RT) in inoperable non-small-cell lung cancer results in a decreased incidental dose deposition in elective nodal stations. While incidental nodal irradiation is considered a relevant by-product of 3D-CRT to control microscopic disease this planning study analyzed the impact of IMRT on dosimetric parameters and tumor control probabilities (TCP) in elective nodal stations in direct comparison with 3D-CRT. The retrospective planning study was performed on 41 patients with NSCLC (stages II-III). The CTV was defined as the primary tumor (GTV + 3 mm) and all FDG-PET-positive lymph node stations. As to the PTV (CTV + 7 mm), both an IMRT plan and a 3D-CRT plan were established. Plans were escalated until the pre-defined dose-constraints of normal tissues (spinal cord, lung, esophagus and heart) were reached. Additionally, IMRT plans were normalized to the total dose of the corresponding 3D-CRT. For two groups of out-of-field mediastinal node stations (all lymph node stations not included in the CTV (LNall-el) and those directly adjacent to the CTV (LNadj-el)) the equivalent uniform dose (EUD) and the TCP (for microscopic disease a D50 of 36.5 Gy was assumed) for the treatment with IMRT vs 3D-CRT were calculated. In comparison, a significantly higher total dose for the PTV could be achieved with the IMRT planning as opposed to conventional 3D-CRT planning (74.3 Gy vs 70.1 Gy; p = 0.03). In identical total reference doses, the EUD of LNadj-el is significantly lower with IMRT than with 3D-CRT (40.4 Gy vs. 44.2 Gy. P = 0.05) and a significant reduction of TCP with IMRT vs 3D-CRT was demonstrated for LNall-el and LNadj-el (12.6 % vs. 14.8 %; and 23.6 % vs 27.3 %, respectively). In comparison with 3D-CRT, IMRT comes along with a decreased EUD in out-of-field lymph node stations. This translates into a statistically significant decrease in TCP-values. Yet, the combination

  9. Short and long time effects of low temperature Plasma Activated Media on 3D multicellular tumor spheroids

    Judée, Florian; Fongia, Céline; Ducommun, Bernard; Yousfi, Mohammed; Lobjois, Valérie; Merbahi, Nofel

    2016-02-01

    This work investigates the regionalized antiproliferative effects of plasma-activated medium (PAM) on colon adenocarcinoma multicellular tumor spheroid (MCTS), a model that mimics 3D organization and regionalization of a microtumor region. PAM was generated by dielectric barrier plasma jet setup crossed by helium carrier gas. MCTS were transferred in PAM at various times after plasma exposure up to 48 hours and effect on MCTS growth and DNA damage were evaluated. We report the impact of plasma exposure duration and delay before transfer on MCTS growth and DNA damage. Local accumulation of DNA damage revealed by histone H2AX phosphorylation is observed on outermost layers and is dependent on plasma exposure. DNA damage is completely reverted by catalase addition indicating that H2O2 plays major role in observed genotoxic effect while growth inhibitory effect is maintained suggesting that it is due to others reactive species. SOD and D-mannitol scavengers also reduced DNA damage by 30% indicating that and OH* are involved in H2O2 formation. Finally, PAM is able to retain its cytotoxic and genotoxic activity upon storage at +4 °C or -80 °C. These results suggest that plasma activated media may be a promising new antitumor strategy for colorectal cancer tumors.

  10. Single minimum incision endoscopic radical nephrectomy for renal tumors with preoperative virtual navigation using 3D-CT volume-rendering

    Shioyama Yasukazu

    2010-04-01

    Full Text Available Abstract Background Single minimum incision endoscopic surgery (MIES involves the use of a flexible high-definition laparoscope to facilitate open surgery. We reviewed our method of radical nephrectomy for renal tumors, which is single MIES combined with preoperative virtual surgery employing three-dimensional CT images reconstructed by the volume rendering method (3D-CT images in order to safely and appropriately approach the renal hilar vessels. We also assessed the usefulness of 3D-CT images. Methods Radical nephrectomy was done by single MIES via the translumbar approach in 80 consecutive patients. We performed the initial 20 MIES nephrectomies without preoperative 3D-CT images and the subsequent 60 MIES nephrectomies with preoperative 3D-CT images for evaluation of the renal hilar vessels and the relation of each tumor to the surrounding structures. On the basis of the 3D information, preoperative virtual surgery was performed with a computer. Results Single MIES nephrectomy was successful in all patients. In the 60 patients who underwent 3D-CT, the number of renal arteries and veins corresponded exactly with the preoperative 3D-CT data (100% sensitivity and 100% specificity. These 60 nephrectomies were completed with a shorter operating time and smaller blood loss than the initial 20 nephrectomies. Conclusions Single MIES radical nephrectomy combined with 3D-CT and virtual surgery achieved a shorter operating time and less blood loss, possibly due to safer and easier handling of the renal hilar vessels.

  11. Dose distribution and tumor control probability in out-of-field lymph node stations in intensity modulated radiotherapy (IMRT) vs 3D-conformal radiotherapy (3D-CRT) of non-small-cell lung cancer: an in silico analysis

    Fleckenstein, Jochen; Eschler, Andrea; Kremp, Katharina; Kremp, Stephanie; Rübe, Christian

    2015-01-01

    Background The advent of IMRT and image-guided radiotherapy (IGRT) in combination with involved-field radiotherapy (IF-RT) in inoperable non-small-cell lung cancer results in a decreased incidental dose deposition in elective nodal stations. While incidental nodal irradiation is considered a relevant by-product of 3D-CRT to control microscopic disease this planning study analyzed the impact of IMRT on dosimetric parameters and tumor control probabilities (TCP) in elective nodal stations in di...

  12. Dose measurements and calculations for tumors within lung: a comparative 3D study for 6 and 18 MV photons

    Purpose/Objective: For treatment of lung cancer, dose heterogeneity corrections and subsequent prescription alteration remain controversial. Previous dosimetry studies based on slab geometry and single beam geometry may not adequately represent the clinical situation of a circumscribed tumor within lung. Energy choice also remains a controversy. The objective of this study was to perform dose measurements for a tumor in lung in an anthropomorphic phantom using a clinically relevant beam arrangement for both 6 and 18 MV photons. Measured and calculated dose distributions were compared, using several different dose calculation algorithms. Methods and Materials: An anthropomorphic phantom was modified by replacing lung cylinders (2.5 and 5.0 cm diameter) with muscle-equivalent cylinders. The phantom was scanned on a CT simulator. Gross, clinical, and planning target volumes (GTV, CTV, PTV1 - tumor and regional nodes plus one cm margin, PTV2 - tumor only plus one cm margin) were delineated slice-by-slice. 3D planning was performed with large fields (AP/PA/RPO) covering PTV1 and boost fields optimized for each PTV2 for 6 and 18 MV photons. Ratio-TAR (RTAR) both with and without heterogeneity corrections, convolution adapted RTAR (CARTAR), and superposition convolution dose calculation algorithms were tested. Film was placed in between phantom slices at the 'tumor' levels. The phantom was irradiated using homogeneous monitor unit calculations. Measured and calculated dose distributions were compared by isodoses and dose volume histograms. One test case (2.5 cm. cylinder) compared film and TLD dose measurements with similar results. Lung-tissue ratio (LTR) measurements with an ion chamber imbedded in a 3 x 3 cm2 muscle-equivalent rectangular solid, surrounded by either lung or muscle-equivalent material, were also performed. Results: The three heterogeneity correction algorithms, compared with the measured isodoses, overpredicted the minimum dose to PTV2 by 11-18% for the

  13. Role of combined DWIBS/3D-CE-T1w whole-body MRI in tumor staging: Comparison with PET-CT

    Objectives: To assess the diagnostic performance of whole-body magnetic resonance imaging (WB-MRI) by diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) in malignant tumor detection and the potential diagnostic advantages in generating fused DWIBS/3D-contrast enhanced T1w (3D-CE-T1w) images. Methods: 45 cancer patients underwent 18F-FDG PET-CT and WB-MRI for staging purpose. Fused DWIBS/3D-CE T1w images were generated off-line. 3D-CE-T1w, DWIBS images alone and fused with 3D-CE T1w were compared by two readers groups for detection of primary diseases and local/distant metastases. Diagnostic performance between the three WB-MRI data sets was assessed using receiver operating characteristic (ROC) curve analysis. Imaging exams and histopathological results were used as standard of references. Results: Areas under the ROC curves of DWIBS vs. 3D-CE-T1w vs. both sequences in fused fashion were 0.97, 0.978, and 1.00, respectively. The diagnostic performance in tumor detection of fused DWIBS/3D-CE-T1w images were statistically superior to DWIBS (p < 0.001) and 3D-CE-T1w (p ≤ 0.002); while the difference between DWIBS and 3D-CE-T1w did not show statistical significance difference. Detection rates of malignancy did not differ between WB-MRI with DWIBS and 18F-FDG PET-CT. Conclusion: WB-MRI with DWIBS is to be considered as alternative tool to conventional whole-body methods for tumor staging and during follow-up in cancer patients.

  14. Role of combined DWIBS/3D-CE-T1w whole-body MRI in tumor staging: Comparison with PET-CT

    Manenti, Guglielmo, E-mail: guggi@tiscali.it [Department of Diagnostic and Molecular Imaging, Interventional Radiology and Radiotherapy, University ' Tor Vergata' , PTV Foundation - Policlinic ' Tor Vergata' , Viale Oxford 81, 00133 Rome (Italy); Ciccio, Carmelo, E-mail: carmeciccio@libero.it [Department of Diagnostic and Molecular Imaging, Interventional Radiology and Radiotherapy, University ' Tor Vergata' , PTV Foundation - Policlinic ' Tor Vergata' , Viale Oxford 81, 00133 Rome (Italy); Squillaci, Ettore, E-mail: ettoresquillaci@tiscali.it [Department of Diagnostic and Molecular Imaging, Interventional Radiology and Radiotherapy, University ' Tor Vergata' , PTV Foundation - Policlinic ' Tor Vergata' , Viale Oxford 81, 00133 Rome (Italy); Strigari, Lidia, E-mail: strigari@ifo.it [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome (Italy); Calabria, Ferdinando, E-mail: ferdinandocalabria@hotmail.it [Department of Diagnostic and Molecular Imaging, Interventional Radiology and Radiotherapy, University ' Tor Vergata' , PTV Foundation - Policlinic ' Tor Vergata' , Viale Oxford 81, 00133 Rome (Italy); Danieli, Roberta, E-mail: roberta.danieli@ptvonline.it [Department of Diagnostic and Molecular Imaging, Interventional Radiology and Radiotherapy, University ' Tor Vergata' , PTV Foundation - Policlinic ' Tor Vergata' , Viale Oxford 81, 00133 Rome (Italy); and others

    2012-08-15

    Objectives: To assess the diagnostic performance of whole-body magnetic resonance imaging (WB-MRI) by diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) in malignant tumor detection and the potential diagnostic advantages in generating fused DWIBS/3D-contrast enhanced T1w (3D-CE-T1w) images. Methods: 45 cancer patients underwent 18F-FDG PET-CT and WB-MRI for staging purpose. Fused DWIBS/3D-CE T1w images were generated off-line. 3D-CE-T1w, DWIBS images alone and fused with 3D-CE T1w were compared by two readers groups for detection of primary diseases and local/distant metastases. Diagnostic performance between the three WB-MRI data sets was assessed using receiver operating characteristic (ROC) curve analysis. Imaging exams and histopathological results were used as standard of references. Results: Areas under the ROC curves of DWIBS vs. 3D-CE-T1w vs. both sequences in fused fashion were 0.97, 0.978, and 1.00, respectively. The diagnostic performance in tumor detection of fused DWIBS/3D-CE-T1w images were statistically superior to DWIBS (p < 0.001) and 3D-CE-T1w (p {<=} 0.002); while the difference between DWIBS and 3D-CE-T1w did not show statistical significance difference. Detection rates of malignancy did not differ between WB-MRI with DWIBS and 18F-FDG PET-CT. Conclusion: WB-MRI with DWIBS is to be considered as alternative tool to conventional whole-body methods for tumor staging and during follow-up in cancer patients.

  15. SU-E-J-200: A Dosimetric Analysis of 3D Versus 4D Image-Based Dose Calculation for Stereotactic Body Radiation Therapy in Lung Tumors

    Ma, M; Rouabhi, O; Flynn, R; Xia, J [University of Iowa Hospitals and Clinics, Iowa City, IA (United States); Bayouth, J [University of Wisconsin, Madison, WI (United States)

    2014-06-01

    Purpose: To evaluate the dosimetric difference between 3D and 4Dweighted dose calculation using patient specific respiratory trace and deformable image registration for stereotactic body radiation therapy in lung tumors. Methods: Two dose calculation techniques, 3D and 4D-weighed dose calculation, were used for dosimetric comparison for 9 lung cancer patients. The magnitude of the tumor motion varied from 3 mm to 23 mm. Breath-hold exhale CT was used for 3D dose calculation with ITV generated from the motion observed from 4D-CT. For 4D-weighted calculation, dose of each binned CT image from the ten breathing amplitudes was first recomputed using the same planning parameters as those used in the 3D calculation. The dose distribution of each binned CT was mapped to the breath-hold CT using deformable image registration. The 4D-weighted dose was computed by summing the deformed doses with the temporal probabilities calculated from their corresponding respiratory traces. Dosimetric evaluation criteria includes lung V20, mean lung dose, and mean tumor dose. Results: Comparing with 3D calculation, lung V20, mean lung dose, and mean tumor dose using 4D-weighted dose calculation were changed by −0.67% ± 2.13%, −4.11% ± 6.94% (−0.36 Gy ± 0.87 Gy), −1.16% ± 1.36%(−0.73 Gy ± 0.85 Gy) accordingly. Conclusion: This work demonstrates that conventional 3D dose calculation method may overestimate the lung V20, MLD, and MTD. The absolute difference between 3D and 4D-weighted dose calculation in lung tumor may not be clinically significant. This research is supported by Siemens Medical Solutions USA, Inc and Iowa Center for Research By Undergraduates.

  16. Precise and real-time measurement of 3D tumor motion in lung due to breathing and heartbeat, measured during radiotherapy

    Purpose: In this work, three-dimensional (3D) motion of lung tumors during radiotherapy in real time was investigated. Understanding the behavior of tumor motion in lung tissue to model tumor movement is necessary for accurate (gated or breath-hold) radiotherapy or CT scanning. Methods: Twenty patients were included in this study. Before treatment, a 2-mm gold marker was implanted in or near the tumor. A real-time tumor tracking system using two fluoroscopy image processor units was installed in the treatment room. The 3D position of the implanted gold marker was determined by using real-time pattern recognition and a calibrated projection geometry. The linear accelerator was triggered to irradiate the tumor only when the gold marker was located within a certain volume. The system provided the coordinates of the gold marker during beam-on and beam-off time in all directions simultaneously, at a sample rate of 30 images per second. The recorded tumor motion was analyzed in terms of the amplitude and curvature of the tumor motion in three directions, the differences in breathing level during treatment, hysteresis (the difference between the inhalation and exhalation trajectory of the tumor), and the amplitude of tumor motion induced by cardiac motion. Results: The average amplitude of the tumor motion was greatest (12±2 mm [SD]) in the cranial-caudal direction for tumors situated in the lower lobes and not attached to rigid structures such as the chest wall or vertebrae. For the lateral and anterior-posterior directions, tumor motion was small both for upper- and lower-lobe tumors (2±1 mm). The time-averaged tumor position was closer to the exhale position, because the tumor spent more time in the exhalation than in the inhalation phase. The tumor motion was modeled as a sinusoidal movement with varying asymmetry. The tumor position in the exhale phase was more stable than the tumor position in the inhale phase during individual treatment fields. However, in many

  17. Dosimetric Comparison Between Intensity-Modulated with Coplanar Field and 3D Conformal Radiotherapy with Noncoplanar Field for Postocular Invasion Tumor

    This study presents a dosimetric optimization effort aiming to compare noncoplanar field (NCF) on 3 dimensions conformal radiotherapy (3D-CRT) and coplanar field (CF) on intensity-modulated radiotherapy (IMRT) planning for postocular invasion tumor. We performed a planning study on the computed tomography data of 8 consecutive patients with localized postocular invasion tumor. Four fields NCF 3D-CRT in the transverse plane with gantry angles of 0-10 deg., 30-45 deg., 240-270 deg., and 310-335 deg. degrees were isocentered at the center of gravity of the target volume. The geometry of the beams was determined by beam's eye view. The same constraints were prepared with between CF IMRT optimization and NCF 3D-CRT treatment. The maximum point doses (D max) for the different optic pathway structures (OPS) with NCF 3D-CRT treatment should differ in no more than 3% from those with the NCF IMRT plan. Dose-volume histograms (DVHs) were obtained for all targets and organ at risk (OAR) with both treatment techniques. Plans with NCF 3D-CRT and CF IMRT constraints on target dose in homogeneity were computed, as well as the conformity index (CI) and homogeneity index (HI) in the target volume. The PTV coverage was optimal with both NCF 3D-CRT and CF IMRT plans in the 8 tumor sites. No difference was noted between the two techniques for the average Dmax and Dmin dose. NCF 3D-CRT and CF IMRT will yield similar results on CI. However, HI was a significant difference between NCF 3D-CRT and CF IMRT plan (p < 0.001). Physical endpoints for target showed the mean target dose to be low in the CF IMRT plan, caused by a large target dose in homogeneity (p < 0.001). The impact of NCF 3D-CRT versus CF IMRT set-up is very slight. NCF3D-CRT is one of the treatment options for postocular invasion tumor. However, constraints for OARs are needed.

  18. Accuracy and inter-observer variability of 3D versus 4D cone-beam CT based image-guidance in SBRT for lung tumors

    Sweeney Reinhart A

    2012-06-01

    Full Text Available Abstract Background To analyze the accuracy and inter-observer variability of image-guidance (IG using 3D or 4D cone-beam CT (CBCT technology in stereotactic body radiotherapy (SBRT for lung tumors. Materials and methods Twenty-one consecutive patients treated with image-guided SBRT for primary and secondary lung tumors were basis for this study. A respiration correlated 4D-CT and planning contours served as reference for all IG techniques. Three IG techniques were performed independently by three radiation oncologists (ROs and three radiotherapy technicians (RTTs. Image-guidance using respiration correlated 4D-CBCT (IG-4D with automatic registration of the planning 4D-CT and the verification 4D-CBCT was considered gold-standard. Results were compared with two IG techniques using 3D-CBCT: 1 manual registration of the planning internal target volume (ITV contour and the motion blurred tumor in the 3D-CBCT (IG-ITV; 2 automatic registration of the planning reference CT image and the verification 3D-CBCT (IG-3D. Image quality of 3D-CBCT and 4D-CBCT images was scored on a scale of 1–3, with 1 being best and 3 being worst quality for visual verification of the IGRT results. Results Image quality was scored significantly worse for 3D-CBCT compared to 4D-CBCT: the worst score of 3 was given in 19 % and 7.1 % observations, respectively. Significant differences in target localization were observed between 4D-CBCT and 3D-CBCT based IG: compared to the reference of IG-4D, tumor positions differed by 1.9 mm ± 0.9 mm (3D vector on average using IG-ITV and by 3.6 mm ± 3.2 mm using IG-3D; results of IG-ITV were significantly closer to the reference IG-4D compared to IG-3D. Differences between the 4D-CBCT and 3D-CBCT techniques increased significantly with larger motion amplitude of the tumor; analogously, differences increased with worse 3D-CBCT image quality scores. Inter-observer variability was largest in SI direction and was

  19. Characterization of novel tumor stroma markers identified by gene expression profiling of human cancer tissues and 3D co-culture models

    The tumor stroma plays an important role in tumorigenesis. During cancer progression it undergoes changes in architecture, gene expression and secretion of proteolytic enzymes that are essential for the invasive and metastatic phenotype of malignant tumors. Cancer associated fibroblasts (Cafes) represent the major cellular component of the stroma and recent studies demonstrated the prognostic and therapeutic significance of CaF-related molecular signatures. The identification and characterization of genes and signaling pathways involved in the molecular interactions between tumor and stromal cells has been the focus of this study. For that purpose we have used two complementary approaches: the identification of novel tumor stroma targets in human colon cancer samples using whole genome Affymetrix GeneChip analysis and the validation of theses targets in a newly established of 3D co-culture model that mimics the cellular and molecular heterogeneity of human cancers. We have demonstrated increased expression of gene sets related to hypoxia, epithelial-to-mesenchymal transition (EMT) and TGFβ pathway activation in CAFs vs their normal counterparts in both systems. The putative TGFβ target IGFBP7 (insulin-like growth factor binding protein 7) was identified as a tumor stroma marker of epithelial cancers and as a tumor antigen in mesenchyme-derived sarcomas. IGFPB7 was shown to promote anchorage-independent growth in malignant mesenchymal cells and malignant epithelial cells with an EMT-phenotype, whereas a tumor suppressor function was observed in tumor epithelial cells. In summary, we have demonstrated that a number of important signaling pathways involved in cancer progression and metastasis are specifically dysregulated in the tumor stroma both in our in vivo screen and in the in vitro 3D model, illustrating the value of these approaches for the identification and characterization of novel stromal markers. (author)

  20. Emergent Stratification in Solid Tumors Selects for Reduced Cohesion of Tumor Cells: A Multi-Cell, Virtual-Tissue Model of Tumor Evolution Using CompuCell3D.

    Maciej H Swat

    Full Text Available Tumor cells and structure both evolve due to heritable variation of cell behaviors and selection over periods of weeks to years (somatic evolution. Micro-environmental factors exert selection pressures on tumor-cell behaviors, which influence both the rate and direction of evolution of specific behaviors, especially the development of tumor-cell aggression and resistance to chemotherapies. In this paper, we present, step-by-step, the development of a multi-cell, virtual-tissue model of tumor somatic evolution, simulated using the open-source CompuCell3D modeling environment. Our model includes essential cell behaviors, microenvironmental components and their interactions. Our model provides a platform for exploring selection pressures leading to the evolution of tumor-cell aggression, showing that emergent stratification into regions with different cell survival rates drives the evolution of less cohesive cells with lower levels of cadherins and higher levels of integrins. Such reduced cohesivity is a key hallmark in the progression of many types of solid tumors.

  1. 1-integrin and MT1-MMP promote tumor cell migration in 2D but not in 3D fibronectin microenvironments

    Corall, Silke; Haraszti, Tamas; Bartoschik, Tanja; Spatz, Joachim Pius; Ludwig, Thomas; Cavalcanti-Adam, Elisabetta Ada

    2014-03-01

    Cell migration is a crucial event for physiological processes, such as embryonic development and wound healing, as well as for pathological processes, such as cancer dissemination and metastasis formation. Cancer cell migration is a result of the concerted action of matrix metalloproteinases (MMPs), expressed by cancer cells to degrade the surrounding matrix, and integrins, the transmembrane receptors responsible for cell binding to matrix proteins. While it is known that cell-microenvironment interactions are essential for migration, the role of the physical state of such interactions remains still unclear. In this study we investigated human fibrosarcoma cell migration in two-dimensional (2D) and three-dimensional (3D) fibronectin (FN) microenvironments. By using antibody blocking approach and cell-binding site mutation, we determined that -integrin is the main mediator of fibrosarcoma cell migration in 2D FN, whereas in 3D fibrillar FN, the binding of - and -integrins is not necessary for cell movement in the fibrillar network. Furthermore, while the general inhibition of MMPs with GM6001 has no effect on cell migration in both 2D and 3D FN matrices, we observed opposing effect after targeted silencing of a membrane-bound MMP, namely MT1-MMP. In 2D fibronectin, silencing of MT1-MMP results in decreased migration speed and loss of directionality, whereas in 3D FN matrices, cell migration speed is increased and integrin-mediated signaling for actin dynamics is promoted. Our results suggest that the fibrillar nature of the matrix governs the migratory behavior of fibrosarcoma cells. Therefore, to hinder migration and dissemination of diseased cells, matrix molecules should be directly targeted, rather than specific subtypes of receptors at the cell membrane.

  2. Comparison of 2D and 3D algorithms for adding a margin to the gross tumor volume in the conformal radiotherapy planning of prostate cancer

    Purpose: To evaluate the adequacy of tumor volume coverage using a three-dimensional (3D) margin-growing algorithm compared to a two-dimensional (2D) margin-growing algorithm in the conformal radiotherapy planning of prostate cancer. Methods and Materials: Two gross tumor volumes (GTV) were segmented in each of 10 patients with localized prostate cancer; prostate gland only (PO) and prostate with seminal vesicles (PSV). A predetermined margin of 10 mm was applied to these two groups (PO and PSV) using both 2D and 3D margin-growing algorithms. The 2D algorithm added a transaxial margin to each GTV slice, whereas the 3D algorithm added a volumetric margin all around the GTV. The true planning target volume (PTV) was defined as the region delineated by the 3D algorithm. The adequacy of geometric coverage of the GTV by the two algorithms was examined in a series of transaxial planes throughout the target volume. Results: The 2D margin-growing algorithm underestimated the PTV by 17% (range 12-20) in the PO group and by 20% (range 13-28) for the PSV group when compared to the 3D-margin algorithm. For the PO group, the mean transaxial difference between the 2D and 3D algorithm was 3.8 mm inferiorly (range 0-20), 1.8 mm centrally (range 0-9), and 4.4 mm superiorly (range 0-22). Considering all of these regions, the mean discrepancy anteriorly was 5.1 mm (range 0-22), posteriorly 2.2 (range 0-20), right border 2.8 mm (range 0-14), and left border 3.1 mm (range 0-12). For the PSV group, the mean discrepancy in the inferior region was 3.8 mm (range 0-20), central region of the prostate was 1.8 mm ( range 0-9), the junction region of the prostate and the seminal vesicles was 5.5 mm (range 0-30), and the superior region of the seminal vesicles was 4.2 mm (range 0-55). When the different borders were considered in the PSV group, the mean discrepancies for the anterior, posterior, right, and left borders were 6.4 mm (range 0-55), 2.5 mm (range 0-20), 2.6 mm (range 0-14), and 3

  3. Tumor control probability and the utility of 4D vs 3D dose calculations for stereotactic body radiotherapy for lung cancer

    Valdes, Gilmer, E-mail: gilmer.valdes@uphs.upenn.edu [Department of Radiation Oncology, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, PA (United States); Robinson, Clifford [Department of Radiation Oncology, Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO (United States); Lee, Percy [Department of Radiation Oncology, David Geffen School of Medicine, UCLA, Los Angeles, CA (United States); Morel, Delphine [Department of Biomedical Engineering, AIX Marseille 2 University, Marseille (France); Department of Medical Physics, Joseph Fourier University, Grenoble (France); Low, Daniel; Iwamoto, Keisuke S.; Lamb, James M. [Department of Radiation Oncology, David Geffen School of Medicine, UCLA, Los Angeles, CA (United States)

    2015-04-01

    Four-dimensional (4D) dose calculations for lung cancer radiotherapy have been technically feasible for a number of years but have not become standard clinical practice. The purpose of this study was to determine if clinically significant differences in tumor control probability (TCP) exist between 3D and 4D dose calculations so as to inform the decision whether 4D dose calculations should be used routinely for treatment planning. Radiotherapy plans for Stage I-II lung cancer were created for 8 patients. Clinically acceptable treatment plans were created with dose calculated on the end-exhale 4D computed tomography (CT) phase using a Monte Carlo algorithm. Dose was then projected onto the remaining 9 phases of 4D-CT using the Monte Carlo algorithm and accumulated onto the end-exhale phase using commercially available deformable registration software. The resulting dose-volume histograms (DVH) of the gross tumor volume (GTV), planning tumor volume (PTV), and PTV{sub setup} were compared according to target coverage and dose. The PTV{sub setup} was defined as a volume including the GTV and a margin for setup uncertainties but not for respiratory motion. TCPs resulting from these DVHs were estimated using a wide range of alphas, betas, and tumor cell densities. Differences of up to 5 Gy were observed between 3D and 4D calculations for a PTV with highly irregular shape. When the TCP was calculated using the resulting DVHs for fractionation schedules typically used in stereotactic body radiation therapy (SBRT), the TCP differed at most by 5% between 4D and 3D cases, and in most cases, it was by less than 1%. We conclude that 4D dose calculations are not necessary for most cases treated with SBRT, but they might be valuable for irregularly shaped target volumes. If 4D calculations are used, 4D DVHs should be evaluated on volumes that include margin for setup uncertainty but not respiratory motion.

  4. Tumor control probability and the utility of 4D vs 3D dose calculations for stereotactic body radiotherapy for lung cancer

    Four-dimensional (4D) dose calculations for lung cancer radiotherapy have been technically feasible for a number of years but have not become standard clinical practice. The purpose of this study was to determine if clinically significant differences in tumor control probability (TCP) exist between 3D and 4D dose calculations so as to inform the decision whether 4D dose calculations should be used routinely for treatment planning. Radiotherapy plans for Stage I-II lung cancer were created for 8 patients. Clinically acceptable treatment plans were created with dose calculated on the end-exhale 4D computed tomography (CT) phase using a Monte Carlo algorithm. Dose was then projected onto the remaining 9 phases of 4D-CT using the Monte Carlo algorithm and accumulated onto the end-exhale phase using commercially available deformable registration software. The resulting dose-volume histograms (DVH) of the gross tumor volume (GTV), planning tumor volume (PTV), and PTVsetup were compared according to target coverage and dose. The PTVsetup was defined as a volume including the GTV and a margin for setup uncertainties but not for respiratory motion. TCPs resulting from these DVHs were estimated using a wide range of alphas, betas, and tumor cell densities. Differences of up to 5 Gy were observed between 3D and 4D calculations for a PTV with highly irregular shape. When the TCP was calculated using the resulting DVHs for fractionation schedules typically used in stereotactic body radiation therapy (SBRT), the TCP differed at most by 5% between 4D and 3D cases, and in most cases, it was by less than 1%. We conclude that 4D dose calculations are not necessary for most cases treated with SBRT, but they might be valuable for irregularly shaped target volumes. If 4D calculations are used, 4D DVHs should be evaluated on volumes that include margin for setup uncertainty but not respiratory motion

  5. Quantitative Assessment of Variational Surface Reconstruction from Sparse Point Clouds in Freehand 3D Ultrasound Imaging during Image-Guided Tumor Ablation

    Shuangcheng Deng

    2016-04-01

    Full Text Available Surface reconstruction for freehand 3D ultrasound is used to provide 3D visualization of a VOI (volume of interest during image-guided tumor ablation surgery. This is a challenge because the recorded 2D B-scans are not only sparse but also non-parallel. To solve this issue, we established a framework to reconstruct the surface of freehand 3D ultrasound imaging in 2011. The key technique for surface reconstruction in that framework is based on variational interpolation presented by Greg Turk for shape transformation and is named Variational Surface Reconstruction (VSR. The main goal of this paper is to evaluate the quality of surface reconstructions, especially when the input data are extremely sparse point clouds from freehand 3D ultrasound imaging, using four methods: Ball Pivoting, Power Crust, Poisson, and VSR. Four experiments are conducted, and quantitative metrics, such as the Hausdorff distance, are introduced for quantitative assessment. The experiment results show that the performance of the proposed VSR method is the best of the four methods at reconstructing surface from sparse data. The VSR method can produce a close approximation to the original surface from as few as two contours, whereas the other three methods fail to do so. The experiment results also illustrate that the reproducibility of the VSR method is the best of the four methods.

  6. Prone Hypofractionated Whole-Breast Radiotherapy Without a Boost to the Tumor Bed: Comparable Toxicity of IMRT Versus a 3D Conformal Technique

    but confirmed benefit in terms of toxicities. If a concurrent boost to the tumor bed is not required, a conformal 3D-CRT approach can adequately deliver prone whole-breast hypofractionation radiotherapy.

  7. Prone Hypofractionated Whole-Breast Radiotherapy Without a Boost to the Tumor Bed: Comparable Toxicity of IMRT Versus a 3D Conformal Technique

    Hardee, Matthew E.; Raza, Shahzad; Becker, Stewart J.; Jozsef, Gabor; Lymberis, Stella C. [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States); Hochman, Tsivia; Goldberg, Judith D. [Division of Biostatistics, New York University School of Medicine, New York, NY (United States); DeWyngaert, Keith J. [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States); Formenti, Silvia C., E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University School of Medicine, New York, NY (United States)

    2012-03-01

    but confirmed benefit in terms of toxicities. If a concurrent boost to the tumor bed is not required, a conformal 3D-CRT approach can adequately deliver prone whole-breast hypofractionation radiotherapy.

  8. Double targeting of Survivin and XIAP radiosensitizes 3D grown human colorectal tumor cells and decreases migration

    Background and purpose: In the present study, we aimed to investigate the effect of single and double knockdown of the inhibitor of apoptosis proteins (IAP) Survivin and X-linked IAP (XIAP) on three-dimensional (3D) clonogenic survival, migration capacity and underlying signaling pathways. Materials and methods: Colorectal cancer cell lines (HCT-15, SW48, SW480, SW620) were subjected to siRNA-mediated single or Survivin/XIAP double knockdown followed by 3D colony forming assays, cell cycle analysis, Caspase activity assays, migration assays, matrigel transmigration assays and Western blotting (Survivin, XIAP, Focal adhesion kinase (FAK), p-FAK Y397, Akt1, p-Akt1 S473, Extracellular signal-regulated kinase (ERK1/2), p-ERK1/2 T202/Y204, Glycogen synthase kinase (GSK)3β, p-GSK3β S9, nuclear factor (NF)-κB p65). Results: While basal cell survival was altered cell line-dependently, Survivin or XIAP single and Survivin/XIAP double knockdown enhanced cellular radiosensitivity of all tested cancer cell lines grown in 3D. Particularly double knockdown conditions revealed accumulation of cells in G2/M, increased subG1 fraction, elevated Caspase 3/7 activity, and reduced migration. Intracellular signaling showed dephosphorylation of FAK and Akt1 upon Survivin and/or Survivin/XIAP silencing. Conclusions: Our results strengthen the notion of Survivin and XIAP to act as radiation resistance factors and further indicate that these apoptosis-regulating proteins are also functioning in cell cycling and cell migration

  9. Comparison of 2D and 3D algorithms for adding a margin to the gross tumor volume in the conformal radiotherapy planning of prostate cancer

    Purpose: To evaluate the adequacy of tumor volume coverage using a three dimensional (3D) margin growing algorithm compared to a two dimensional (2D) margin growing algorithm in the conformal radiotherapy planning of prostate cancer. Methods and Materials: Two gross tumor volumes (GTV) were segmented in each of ten patients with localized prostate cancer: prostate gland only (PO) and prostate with seminal vesicles (PSV). A margin of 10 mm was applied to these two groups (PO and PSV) using both the 2D and 3D margin growing algorithms. The true planning target volume (PTV) was defined as the region delineated by the 3D algorithm. Adequacy of geometric coverage of the GTV with the two algorithms was examined throughout the target volume. Discrepancies between the two margin methods were measured in the transaxial plane. Results: The 2D algorithm underestimated the PTV by 17% (range 12-20) in the PO group and by 20% (range 13-28) for the PSV group when compared to the 3D algorithm. For both the PO and PSV groups, the inferior coverage of the PTV was consistently underestimated by the 2D margin algorithm when compared to the 3D margins with a mean radial distance of 4.8 mm (range 0-10). In the central region of the prostate gland, the anterior, posterior, and lateral PTV borders were underestimated with the 2D margin in both the PO and PSV groups by a mean of 3.6 mm (range 0-9), 2.1 mm (range 0-8), and 1.8 (range 0-9) respectively. The PTV coverage of the PO group superiorly was radially underestimated by 4.5mm (range 0-14) when comparing the 2D margins to the 3D margins. For the PSV group, the junction region between the prostate and the seminal vesicles was underestimated by the 2D margin by a mean transaxial distance of 18.1 mm in the anterior PTV border (range 4-30), 7.2 mm posteriorly (range 0-20), and 3.7 mm laterally (range 0-14). The superior region of the seminal vesicles in the PSV group was also consistently underestimated with a radial discrepancy of 3.3 mm

  10. Fully Automated One-Step Production of Functional 3D Tumor Spheroids for High-Content Screening.

    Monjaret, François; Fernandes, Mathieu; Duchemin-Pelletier, Eve; Argento, Amelie; Degot, Sébastien; Young, Joanne

    2016-04-01

    Adoption of spheroids within high-content screening (HCS) has lagged behind high-throughput screening (HTS) due to issues with running complex assays on large three-dimensional (3D) structures.To enable multiplexed imaging and analysis of spheroids, different cancer cell lines were grown in 3D on micropatterned 96-well plates with automated production of nine uniform spheroids per well. Spheroids achieve diameters of up to 600 µm, and reproducibility was experimentally validated (interwell and interplate CV(diameter) imaging confirmed that micropatterned spheroids exhibit characteristic cell heterogeneity with distinct microregions. Furthermore, central necrosis appears at a consistent spheroid size, suggesting standardized growth.Using three reference compounds (fluorouracil, irinotecan, and staurosporine), we validated HT-29 micropatterned spheroids on an HCS platform, benchmarking against hanging-drop spheroids. Spheroid formation and imaging in a single plate accelerate assay workflow, and fixed positioning prevents structures from overlapping or sticking to the well wall, augmenting image processing reliability. Furthermore, multiple spheroids per well increase the statistical confidence sufficiently to discriminate compound mechanisms of action and generate EC50 values for endpoints of cell death, architectural change, and size within a single-pass read. Higher quality data and a more efficient HCS work chain should encourage integration of micropatterned spheroid models within fundamental research and drug discovery applications. PMID:26385905

  11. Development of a new rapid isolation device for circulating tumor cells (CTCs using 3D palladium filter and its application for genetic analysis.

    Akiko Yusa

    Full Text Available Circulating tumor cells (CTCs in the blood of patients with epithelial malignancies provide a promising and minimally invasive source for early detection of metastasis, monitoring of therapeutic effects and basic research addressing the mechanism of metastasis. In this study, we developed a new filtration-based, sensitive CTC isolation device. This device consists of a 3-dimensional (3D palladium (Pd filter with an 8 µm-sized pore in the lower layer and a 30 µm-sized pocket in the upper layer to trap CTCs on a filter micro-fabricated by precise lithography plus electroforming process. This is a simple pump-less device driven by gravity flow and can enrich CTCs from whole blood within 20 min. After on-device staining of CTCs for 30 min, the filter cassette was removed from the device, fixed in a cassette holder and set up on the upright fluorescence microscope. Enumeration and isolation of CTCs for subsequent genetic analysis from the beginning were completed within 1.5 hr and 2 hr, respectively. Cell spike experiments demonstrated that the recovery rate of tumor cells from blood by this Pd filter device was more than 85%. Single living tumor cells were efficiently isolated from these spiked tumor cells by a micromanipulator, and KRAS mutation, HER2 gene amplification and overexpression, for example, were successfully detected from such isolated single tumor cells. Sequential analysis of blood from mice bearing metastasis revealed that CTC increased with progression of metastasis. Furthermore, a significant increase in the number of CTCs from the blood of patients with metastatic breast cancer was observed compared with patients without metastasis and healthy volunteers. These results suggest that this new 3D Pd filter-based device would be a useful tool for the rapid, cost effective and sensitive detection, enumeration, isolation and genetic analysis of CTCs from peripheral blood in both preclinical and clinical settings.

  12. A dose-volume intercomparison of volumetric-modulated arc therapy, 3D static conformal, and rotational conformal techniques for portal vein tumor thrombus in hepatocellular carcinoma

    We created volumetric-modulated arc therapy (VMAT) plans for portal vein tumor thrombus (PVTT) in hepatocellular carcinoma, and compared the results with those from three-dimensional conformal radiotherapy (3D-CRT) and rotational conformal radiotherapy (R-CRT) plans. CT scan data from 10 consecutive patients with PVTT treated with 3D-CRT between January 2008 and January 2010 were utilized in the analysis. We analyzed the dosimetric properties of the plans for the 10 patients using the three different techniques with three different isocenter doses of 50, 56 and 60 Gy in 2-Gy fractions. The D95, Dmean, homogeneity index and conformity index were compared for the planning target volume (PTV). The Dmean, V20 and V30 were also compared for normal livers. The monitor units (MUs) and the treatment time were also evaluated. The normal liver V30 for VMAT was significantly less than that for 3D-CRT for the prescribed doses of 56 and 60 Gy (P<0.05). It was also found that the normal liver V30 resulting from 3D-CRT was prohibitively increased when the prescribed dose was increased in two steps. For PTV D95, we found no significant differences between the three techniques for the 50- and 56-Gy prescriptions, or between VMAT and the other techniques for the 60-Gy prescription. The differences in the MUs and treatment times were not statistically significant between VMAT and 3D-CRT. We have demonstrated that VMAT may be a more advantageous technique for dose escalation reaching 60 Gy in the treatment of PVTT due to the reduced normal liver V30. (author)

  13. AP-PA field orientation followed by IMRT reduces lung exposure in comparison to conventional 3D conformal and sole IMRT in centrally located lung tumors

    Little attention has been paid to the fact that intensity modulated radiation therapy (IMRT) techniques do not easily enable treatment with opposed beams. Three treatment plans (3 D conformal, IMRT, and combined (anterior-posterior-posterio-anterior (AP-PA) + IMRT) of 7 patients with centrally-located lung cancer were compared for exposure of lung, spinal cord and esophagus. Combined IMRT and AP-PA techniques offer better lung tissue sparing compared to plans predicated solely on IMRT for centrally-located lung tumors

  14. AP-PA field orientation followed by IMRT reduces lung exposure in comparison to conventional 3D conformal and sole IMRT in centrally located lung tumors.

    Soyfer, Viacheslav; Meir, Yaron; Corn, Benjamin W; Schifter, Dan; Gez, Eliahu; Tempelhoff, Haim; Shtraus, Natan

    2012-01-01

    Little attention has been paid to the fact that intensity modulated radiation therapy (IMRT) techniques do not easily enable treatment with opposed beams. Three treatment plans (3 D conformal, IMRT, and combined (anterior-posterior-posterio-anterior (AP-PA) + IMRT) of 7 patients with centrally-located lung cancer were compared for exposure of lung, spinal cord and esophagus. Combined IMRT and AP-PA techniques offer better lung tissue sparing compared to plans predicated solely on IMRT for centrally-located lung tumors. PMID:22340727

  15. AP-PA field orientation followed by IMRT reduces lung exposure in comparison to conventional 3D conformal and sole IMRT in centrally located lung tumors

    Soyfer Viacheslav

    2012-02-01

    Full Text Available Abstract Little attention has been paid to the fact that intensity modulated radiation therapy (IMRT techniques do not easily enable treatment with opposed beams. Three treatment plans (3 D conformal, IMRT, and combined (anterior-posterior-posterio-anterior (AP-PA + IMRT of 7 patients with centrally-located lung cancer were compared for exposure of lung, spinal cord and esophagus. Combined IMRT and AP-PA techniques offer better lung tissue sparing compared to plans predicated solely on IMRT for centrally-located lung tumors.

  16. 3D viability imaging of tumor phantoms treated with single-walled carbon nanohorns and photothermal therapy

    A new image analysis method called the spatial phantom evaluation of cellular thermal response in layers (SPECTRL) is presented for assessing spatial viability response to nanoparticle enhanced photothermal therapy in tissue representative phantoms. Sodium alginate phantoms seeded with MDA-MB-231 breast cancer cells and single-walled nanohorns were laser irradiated with an ytterbium fiber laser at a wavelength of 1064 nm and irradiance of 3.8 W cm−2 for 10–80 s. SPECTRL quantitatively assessed and correlated 3D viability with spatiotemporal temperature. Based on this analysis, kill and transition zones increased from 3.7 mm3 and 13 mm3 respectively to 44.5 mm3 and 44.3 mm3 as duration was increased from 10 to 80 s. SPECTRL provides a quantitative tool for measuring precise spatial treatment regions, providing information necessary to tailor therapy protocols. (paper)

  17. 3D viability imaging of tumor phantoms treated with single-walled carbon nanohorns and photothermal therapy

    Whitney, Jon; DeWitt, Matthew; Whited, Bryce M.; Carswell, William; Simon, Alex; Rylander, Christopher G.; Rylander, Marissa Nichole

    2013-07-01

    A new image analysis method called the spatial phantom evaluation of cellular thermal response in layers (SPECTRL) is presented for assessing spatial viability response to nanoparticle enhanced photothermal therapy in tissue representative phantoms. Sodium alginate phantoms seeded with MDA-MB-231 breast cancer cells and single-walled nanohorns were laser irradiated with an ytterbium fiber laser at a wavelength of 1064 nm and irradiance of 3.8 W cm-2 for 10-80 s. SPECTRL quantitatively assessed and correlated 3D viability with spatiotemporal temperature. Based on this analysis, kill and transition zones increased from 3.7 mm3 and 13 mm3 respectively to 44.5 mm3 and 44.3 mm3 as duration was increased from 10 to 80 s. SPECTRL provides a quantitative tool for measuring precise spatial treatment regions, providing information necessary to tailor therapy protocols.

  18. QUANTOM - improved tumor diagnosis by quantitative evaluation of tomography data using digital 3D image processing. Final report

    Nonlinear techniques are applied to tasks in medical image processing. Using the so-called scaling index method and scaling vector method segmentation and detection algorithms are developed in order to recognise and measure tumors in three-dimensional tomographic data sets. It is shown that pulmonary nodules can well be detected in the lung only by analysing their morphological structure. Especially the nodules can be discriminated from the bronchovascular structures, which have the same intensity in the data sets. Newly developed segmentation algorithms, with which an exact volumetric assessment of tumors is made possible, are presented. It turns out that an algorithm, which combines elements from the watershed-transformation and from region growing techniques, yields the best results in terms of accuracy, transparency and reproducibility. The clinical valence of the volumetry is illustrated with studies concerning the response evaluation of tumors of the gastrointestinal tract during (chemo-)therapy. It turns out that the results obtained with an exact three-dimensional volume determination are in much better agreement with the histological gold standard than those obtained with simple conventional, planimetric measurements. Furthermore the specificity of the prediction for the response to a chosen therapy can be significantly increased using CT-volumetry and PET-measurements. Therefore, the number of therapeutically questionable operations can be reduced. Further possible fields of application for the newly developed methods are presented. (orig.)

  19. 关于股骨头坏死、骨髓炎、脑垂体瘤、尿崩症的患者临床观察与宣教%Patients with Clinical Observation and Education on Avascular Necrosis of the Femoral Head, Osteomyelitis, Pituitary tumor, Diabetes insipidus

    李娟

    2015-01-01

    Through the introduction of avascular necrosis of the femoral head, osteomyelitis, pituitary tumor and diabetes insipidus(DI)in patients with clinical observation process and the nursing operation technique, explains the related health care workers to guide the patients correctly understand the disease, establish the confidence to overcome the disease’s method.%通过介绍股骨头坏死、骨髓炎、脑垂体瘤和尿崩症(DI)患者的临床观察过程和护理操作技术,阐述了相关医护工作者指导患者正确认识疾病、树立战胜疾病信心的方法。

  20. Real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy

    Li, Ruijiang; Lewis, John H; Gu, Xuejun; Folkerts, Michael; Men, Chunhua; Jiang, Steve B

    2010-01-01

    Purpose: To develop an algorithm for real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy. Methods: Given a set of volumetric images of a patient at N breathing phases as the training data, we perform deformable image registration between a reference phase and the other N-1 phases, resulting in N-1 deformation vector fields (DVFs). These DVFs can be represented efficiently by a few eigenvectors and coefficients obtained from principal component analysis (PCA). By varying the PCA coefficients, we can generate new DVFs, which, when applied on the reference image, lead to new volumetric images. We then can reconstruct a volumetric image from a single projection image by optimizing the PCA coefficients such that its computed projection matches the measured one. The 3D location of the tumor can be derived by applying the inverted DVF on its position in the reference image. Our algorithm was implemented on graphics processing units...

  1. Evaluation of anti-HER2 scFv-conjugated PLGA-PEG nanoparticles on 3D tumor spheroids of BT474 and HCT116 cancer cells

    Thuy Duong Le, Thi; Pham, Thu Hong; Nghia Nguyen, Trong; Giang Ngo, Thi Hong; Nhung Hoang, Thi My; Huan Le, Quang

    2016-06-01

    Three-dimensional culture cells (spheroids) are one of the multicellular culture models that can be applied to anticancer chemotherapeutic development. Multicellular spheroids more closely mimic in vivo tumor-like patterns of physiologic environment and morphology. In previous research, we designed docetaxel-loaded pegylated poly(D, L-lactide-co-glycolide) nanoparticles conjugated with anti-HER2 single chain antibodies (scFv-Doc-PLGA-PEG) and evaluated them in 2D cell culture. In this study, we continuously evaluate the cellular uptake and cytotoxic effect of scFv-Doc-PLGA-PEG on a 3D tumor spheroid model of BT474 (HER2-overexpressing) and HCT116 (HER2-underexpressing) cancer cells. The results showed that the nanoparticle formulation conjugated with scFv had a significant internalization effect on the spheroids of HER2-overexpressing cancer cells as compared to the spheroids of HER2-underexpressing cancer cells. Therefore, cytotoxic effects of targeted nanoparticles decreased the size and increased necrotic score of HER2-overexpressing tumor spheroids. Thus, these scFv-Doc-PLGA-PEG nanoparticles have potential for active targeting for HER2-overexpressing cancer therapy. In addition, BT474 and HCT116 spheroids can be used as a tumor model for evaluation of targeting therapies.

  2. Image-guided installation of 3D-printed patient-specific implant and its application in pelvic tumor resection and reconstruction surgery.

    Chen, Xiaojun; Xu, Lu; Wang, Yiping; Hao, Yongqiang; Wang, Liao

    2016-03-01

    Nowadays, the diagnosis and treatment of pelvic sarcoma pose a major surgical challenge for reconstruction in orthopedics. With the development of manufacturing technology, the metal 3D-printed customized implants have brought revolution for the limb-salvage resection and reconstruction surgery. However, the tumor resection is not without risk and the precise implant placement is very difficult due to the anatomic intricacies of the pelvis. In this study, a surgical navigation system including the implant calibration algorithm has been developed, so that the surgical instruments and the 3D-printed customized implant can be tracked and rendered on the computer screen in real time, minimizing the risks and improving the precision of the surgery. Both the phantom experiment and the pilot clinical case study presented the feasibility of our computer-aided surgical navigation system. According to the accuracy evaluation experiment, the precision of customized implant installation can be improved three to five times (TRE: 0.75±0.18 mm) compared with the non-navigated implant installation after the guided osteotomy (TRE: 3.13±1.28 mm), which means it is sufficient to meet the clinical requirements of the pelvic reconstruction. However, more clinical trials will be conducted in the future work for the validation of the reliability and efficiency of our navigation system. PMID:26652978

  3. A 3D graphene oxide microchip and a Au-enwrapped silica nanocomposite-based supersandwich cytosensor toward capture and analysis of circulating tumor cells

    Li, Na; Xiao, Tingyu; Zhang, Zhengtao; He, Rongxiang; Wen, Dan; Cao, Yiping; Zhang, Weiying; Chen, Yong

    2015-10-01

    Determination of the presence and number of circulating tumor cells (CTCs) in peripheral blood can provide clinically important data for prognosis and therapeutic response patterns. In this study, a versatile supersandwich cytosensor was successfully developed for the highly sensitive and selective analysis of CTCs using Au-enwrapped silica nanocomposites (Si/AuNPs) and three-dimensional (3D) microchips. First, 3D microchips were fabricated by a photolithography method. Then, the prepared substrate was applied to bind graphene oxide, streptavidin and biotinylated epithelial-cell adhesion-molecule antibody, resulting in high stability, bioactivity, and capability for CTCs capture. Furthermore, horseradish peroxidase and anti-CA153 were co-linked to the Si/AuNPs for signal amplification. The performance of the cytosensor was evaluated with MCF7 breast cancer cells. Under optimal conditions, the proposed supersandwich cytosensor showed high sensitivity with a wide range of 101 to 107 cells per mL and a detection limit of 10 cells per mL. More importantly, it could effectively distinguish CTCs from normal cells, which indicated the promising applications of our method for the clinical diagnosis and therapeutic monitoring of cancers.

  4. Overcoming therapeutic resistance in pancreatic cancer is not a simple mix of PDT and chemotherapy: Evaluation of PDT-chemotherapy combinations in 3D tumor models

    Celli, Jonathan P.; Petrovic, Ljubica; Massdodi, Iqbal; Rizvi, Imran; Hasan, Tayyaba

    2013-03-01

    The dismal survival statistics for pancreatic cancer are due in large part to the notoriously poor response of these tumors to conventional therapies. Here we examine the ability of photodynamic therapy (PDT), using the photosensitizer verteporfin to enhance of the efficacy of traditional chemotherapy agents and/or eradicate populations that are nonresponsive to these agents. Using an in vitro 3D tumor model of pancreatic cancer combined with an imaging-based methodology for quantifying therapeutic response, we specifically examine PDT combination treatments with gemcitabine and oxaliplatin. We show that our 3D cell culture model recapitulates a more clinically-relevant dose response to gemcitabine, with minimal cytotoxic response even at high doses. The same cultures exhibit modest response to PDT treatments, but are also less responsive to this modality relative to our previous reports of monolayer dose response in the same cells. In combination we found no evidence of any enhancement in efficacy of either PDT or gemcitabine treatment regardless of dose or sequence (PDT before gemcitabine, or gemcitabine before PDT). However, when oxaliplatin chemotherapy was administered immediately after treatment with 2.5J/cm2 verteporfin PDT, there was an observable enhancement in response that appears to exceed the additive combination of either treatment alone and suggesting there may be a synergistic interaction. This observation is consistent with previous reports of enhanced efficacy in combinations of PDT with platinum-based chemotherapy. The contrast in results between the combinations examined here underscores the need for rational design of mechanism-based PDT combinations.

  5. 3 D打印技术在肾肿瘤治疗的应用%The Application of 3 D Printing Technology in Renal Tumor Treatment

    王锋; 赵淼; 马静

    2016-01-01

    Objective To analysis the application of 3 D printing in renal tumor treatment.Methods Selected 48 patients with renal tumors, according to the random distribution divided into research group (24 cases) and control group (24 cases) and control group received MRI and CT reconstruction image analysis, the study group received 3 D printing technology reconstruction image analysis, compared two groups ofoperation indicators. Results Through the analysis, the team estimated blood loss, blocking blood lfow to the time, operation time, blood creatinine levels and the incidence of adverse reactions were lower than those of the control group obviously (P<0.05). Conclusion In the treatment for kidney cancer, 3 D printing technology in the preoperative simulation and resection of guidance, can reduce the risk of surgery, reduce the rate of renal injury.%目的:分析3 D打印技术在肾肿瘤治疗中的应用效果。方法选取我院48例肾肿瘤患者,按照随机分配,分为研究组(24例)和对照组(24例),对照组通过MRI和CT重建图像分析,研究组通过3 D打印技术重建图像分析,对比两组手术指标。结果经分析,研究组估计出血量、血流阻断时间、手术时间、血肌酐水平和不良反应发生率比对照组更低,两组对比差异存在统计学意义(P<0.05)。结论对于肾肿瘤治疗,3 D打印技术在术前模拟和切除术指导,可减少手术风险,降低肾功能损伤率。

  6. New-generation taxoid SB-T-1214 inhibits stem cell-related gene expression in 3D cancer spheroids induced by purified colon tumor-initiating cells

    Rowehl Rebecca A

    2010-07-01

    Full Text Available Abstract Background Growing evidence suggests that the majority of tumors are organized hierarchically, comprising a population of tumor-initiating, or cancer stem cells (CSCs responsible for tumor development, maintenance and resistance to drugs. Previously we have shown that the CD133high/CD44high fraction of colon cancer cells is different from their bulk counterparts at the functional, morphological and genomic levels. In contrast to the majority of colon cancer cells expressing moderate levels of CD133, CD44 and CD166, cells with a high combined expression of CD133 and CD44 possessed several characteristic stem cell features, including profound self-renewal capacity in vivo and in vitro, and the ability to give rise to different cell phenotypes. The present study was undertaken for two aims: a to determine stem cell-related genomic characteristics of floating 3D multicellular spheroids induced by CD133high/CD44high colon cancer cells; and b to evaluate CSC-specific alterations induced by new-generation taxoid SB-T-1214. Results Selected CSC phenotype was isolated from three independent invasive colon cancer cell lines, HCT116, HT29 and DLD-1. A stem cell-specific PCR array assay (SABiosciences revealed that colonospheres induced by purified CD133high/CD44high expressing cells display profound up-regulation of stem cell-related genes in comparison with their bulk counterparts. The FACS analysis has shown that the 3D colonospheres contained some minority cell populations with high levels of expression of Oct4, Sox2, Nanog and c-Myc, which are essential for stem cell pluripotency and self-renewal. Single administration of the SB-T-1214 at concentration 100 nM-1 μM for 48 hr not only induced growth inhibition and apoptotic cell death in these three types of colon cancer spheroids in 3D culture, but also mediated massive inhibition of the stem cell-related genes and significant down-regulation of the pluripotency gene expression. PCR array and

  7. Avascular necrosis of the femoral head presenting as trochanteric bursitis.

    Mandell, B F

    1990-01-01

    Five patients are described with avascular necrosis of the femoral head who presented with ipsilateral trochanteric bursitis, in the absence of clearcut hip joint disease. Avascular necrosis was indicated by magnetic resonance imaging. It is suggested that clinical trochanteric bursitis, especially when refractory to local corticosteroid treatment, may be the initial sign of hip disease. In the patient with risk factor(s) for avascular necrosis that diagnosis should be considered and evaluate...

  8. Comparison of stereotactic radiosurgery and fractionated stereotactic radiotherapy of acoustic neurinomas according to 3-D tumor volume shrinkage and quality of life

    Henzel, Martin; Engenhart-Cabillic, Rita [Dept. of Radiation Oncology, Philipps Univ. Marburg (Germany); Hamm, Klaus; Surber, Gunnar; Kleinert, Gabriele [Dept. of Stereotactic Neurosurgery and Radiosurgery, HELIOS Klinikum, Erfurt (Germany); Sitter, Helmut [Dept. of Theoretical Surgery, Philipps Univ. Marburg (Germany); Gross, Markus W. [Dept. of Radiation Oncology, Philipps Univ. Marburg (Germany); Dept. of Radio-Oncology, Univ. Hospital of Basel (Switzerland)

    2009-09-15

    Background and purpose: stereotactic radiosurgery (SRS) and also fractionated stereotactic radiotherapy (SRT) offer high local control (LC) rates (> 90%). This study aimed to evaluate three-dimensional (3-D) tumor volume (TV) shrinkage and to assess quality of life (QoL) after SRS/SRT. Patients and methods: from 1999 to 2005, 35/74 patients were treated with SRS, and 39/74 with SRT. Median age was 60 years. Treatment was delivered by a linear accelerator. Median single dose was 13 Gy (SRS) or 54 Gy (SRT). Patients were followed up {>=} 12 months after SRS/SRT. LC and toxicity were evaluated by clinical examinations and magnetic resonance imaging. 3-D TV shrinkage was evaluated with the planning system. QoL was assessed using the questionnaire Short Form-36. Results: Median follow-up was 50/36 months (SRS/SRT). Actuarial 5-year freedom from progression/overall survival was 88.1%/100% (SRS), and 87.5%/87.2% (SRT). TV shrinkage was 15.1%/40.7% (SRS/SRT; p = 0.01). Single dose (< 13 Gy) was the only determinant factor for TV shrinkage after SRS (p = 0.001). Age, gender, initial TV, and previous operations did not affect TV shrinkage. Acute or late toxicity ({>=} grade 3) was never seen. Concerning QoL, no significant differences were observed after SRS/SRT. Previous operations and gender did not affect QoL (p > 0.05). Compared with the German normal population, patients had worse values for all domains except for mental health. Conclusion: TV shrinkage was significantly higher after SRT than after SRS. Main symptoms were not affected by SRS/SRT. Retrospectively, QoL was neither affected by SRS nor by SRT. (orig.)

  9. A fully automatic, threshold-based segmentation method for the estimation of the Metabolic Tumor Volume from PET images: validation on 3D printed anthropomorphic oncological lesions

    Gallivanone, F.; Interlenghi, M.; Canervari, C.; Castiglioni, I.

    2016-01-01

    18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET) is a standard functional diagnostic technique to in vivo image cancer. Different quantitative paramters can be extracted from PET images and used as in vivo cancer biomarkers. Between PET biomarkers Metabolic Tumor Volume (MTV) has gained an important role in particular considering the development of patient-personalized radiotherapy treatment for non-homogeneous dose delivery. Different imaging processing methods have been developed to define MTV. The different proposed PET segmentation strategies were validated in ideal condition (e.g. in spherical objects with uniform radioactivity concentration), while the majority of cancer lesions doesn't fulfill these requirements. In this context, this work has a twofold objective: 1) to implement and optimize a fully automatic, threshold-based segmentation method for the estimation of MTV, feasible in clinical practice 2) to develop a strategy to obtain anthropomorphic phantoms, including non-spherical and non-uniform objects, miming realistic oncological patient conditions. The developed PET segmentation algorithm combines an automatic threshold-based algorithm for the definition of MTV and a k-means clustering algorithm for the estimation of the background. The method is based on parameters always available in clinical studies and was calibrated using NEMA IQ Phantom. Validation of the method was performed both in ideal (e.g. in spherical objects with uniform radioactivity concentration) and non-ideal (e.g. in non-spherical objects with a non-uniform radioactivity concentration) conditions. The strategy to obtain a phantom with synthetic realistic lesions (e.g. with irregular shape and a non-homogeneous uptake) consisted into the combined use of standard anthropomorphic phantoms commercially and irregular molds generated using 3D printer technology and filled with a radioactive chromatic alginate. The proposed segmentation algorithm was feasible in a

  10. Real-time intensity based 2D/3D registration using kV-MV image pairs for tumor motion tracking in image guided radiotherapy

    Furtado, H.; Steiner, E.; Stock, M.; Georg, D.; Birkfellner, W.

    2014-03-01

    Intra-fractional respiratorymotion during radiotherapy is one of themain sources of uncertainty in dose application creating the need to extend themargins of the planning target volume (PTV). Real-time tumormotion tracking by 2D/3D registration using on-board kilo-voltage (kV) imaging can lead to a reduction of the PTV. One limitation of this technique when using one projection image, is the inability to resolve motion along the imaging beam axis. We present a retrospective patient study to investigate the impact of paired portal mega-voltage (MV) and kV images, on registration accuracy. We used data from eighteen patients suffering from non small cell lung cancer undergoing regular treatment at our center. For each patient we acquired a planning CT and sequences of kV and MV images during treatment. Our evaluation consisted of comparing the accuracy of motion tracking in 6 degrees-of-freedom(DOF) using the anterior-posterior (AP) kV sequence or the sequence of kV-MV image pairs. We use graphics processing unit rendering for real-time performance. Motion along cranial-caudal direction could accurately be extracted when using only the kV sequence but in AP direction we obtained large errors. When using kV-MV pairs, the average error was reduced from 3.3 mm to 1.8 mm and the motion along AP was successfully extracted. The mean registration time was of 190+/-35ms. Our evaluation shows that using kVMV image pairs leads to improved motion extraction in 6 DOF. Therefore, this approach is suitable for accurate, real-time tumor motion tracking with a conventional LINAC.

  11. 3D video

    Lucas, Laurent; Loscos, Céline

    2013-01-01

    While 3D vision has existed for many years, the use of 3D cameras and video-based modeling by the film industry has induced an explosion of interest for 3D acquisition technology, 3D content and 3D displays. As such, 3D video has become one of the new technology trends of this century.The chapters in this book cover a large spectrum of areas connected to 3D video, which are presented both theoretically and technologically, while taking into account both physiological and perceptual aspects. Stepping away from traditional 3D vision, the authors, all currently involved in these areas, provide th

  12. 3D Animation Essentials

    Beane, Andy

    2012-01-01

    The essential fundamentals of 3D animation for aspiring 3D artists 3D is everywhere--video games, movie and television special effects, mobile devices, etc. Many aspiring artists and animators have grown up with 3D and computers, and naturally gravitate to this field as their area of interest. Bringing a blend of studio and classroom experience to offer you thorough coverage of the 3D animation industry, this must-have book shows you what it takes to create compelling and realistic 3D imagery. Serves as the first step to understanding the language of 3D and computer graphics (CG)Covers 3D anim

  13. Avascular osteonecrosis of the femoral condyle after arthroscopic surgery

    Avascular osteonecrosis of the femoral condyle after arthroscopic surgery. Retrospective review of 10 patients who presented with avascular necrosis of the ipsilateral femoral condyle following arthroscopic meniscectomy (9 medial, 1 lateral). The bone lesions were evaluated by radiography and MRI, which were repeated for few patients. MRI allows earlier diagnosis of avascular necrosis of the femoral condyle and offers an evaluation of extent of the lesions whose evolution is variable: 3 patients required a knee prosthesis, the other 7 patients were treated medically. (authors)

  14. Changes in Global Gene Expression Associated with 3D Structure of Tumors: An Ex Vivo Matrix-Free Mesothelioma Spheroid Model

    Heungnam Kim; Yen Phung; Mitchell Ho

    2012-01-01

    Tumor microenvironments present significant barriers to anti-tumor agents. Molecules involved in multicellular tumor microenvironments, however, are difficult to study ex vivo. Here, we generated a matrix-free tumor spheroid model using the NCI-H226 mesothelioma cell line and compared the gene expression profiles of spheroids and monolayers using microarray analysis. Microarray analysis revealed that 142 probe sets were differentially expressed between tumor spheroids and monolayers. Gene ont...

  15. EUROPEANA AND 3D

    D. Pletinckx

    2012-09-01

    Full Text Available The current 3D hype creates a lot of interest in 3D. People go to 3D movies, but are we ready to use 3D in our homes, in our offices, in our communication? Are we ready to deliver real 3D to a general public and use interactive 3D in a meaningful way to enjoy, learn, communicate? The CARARE project is realising this for the moment in the domain of monuments and archaeology, so that real 3D of archaeological sites and European monuments will be available to the general public by 2012. There are several aspects to this endeavour. First of all is the technical aspect of flawlessly delivering 3D content over all platforms and operating systems, without installing software. We have currently a working solution in PDF, but HTML5 will probably be the future. Secondly, there is still little knowledge on how to create 3D learning objects, 3D tourist information or 3D scholarly communication. We are still in a prototype phase when it comes to integrate 3D objects in physical or virtual museums. Nevertheless, Europeana has a tremendous potential as a multi-facetted virtual museum. Finally, 3D has a large potential to act as a hub of information, linking to related 2D imagery, texts, video, sound. We describe how to create such rich, explorable 3D objects that can be used intuitively by the generic Europeana user and what metadata is needed to support the semantic linking.

  16. Solid works 3D

    This book explains modeling of solid works 3D and application of 3D CAD/CAM. The contents of this book are outline of modeling such as CAD and 2D and 3D, solid works composition, method of sketch, writing measurement fixing, selecting projection, choosing condition of restriction, practice of sketch, making parts, reforming parts, modeling 3D, revising 3D modeling, using pattern function, modeling necessaries, assembling, floor plan, 3D modeling method, practice floor plans for industrial engineer data aided manufacturing, processing of CAD/CAM interface.

  17. Combination of cross-sectional MRI, MRCP and gadolinium-enhanced dual-phase 3D-MRA in the staging of pancreatic tumors: first clinical results; Kombinierter Einsatz von MRT, MRCP und kontrastverstaerkter 2-Phasen 3D-MRA in der Diagnostik von Pankreastumoren: Erste klinische Ergebnisse

    Gaa, J.; Tesdal, I.K.; Lehmann, K.J.; Boehm, C.; Moeckel, R.; Georgi, M. [Klinikum Mannheim gGmbH (Germany). Inst. fuer Klinische Radiologie; Wendl, K.; Meier-Willersen, H.J.; Richter, A.; Trede, M. [Klinikum Mannheim gGmbH (Germany). Chirurgische Klinik

    1999-06-01

    Purpose: To evaluate the accuracy of a non-invasive `all-in-one` staging MR method in patients with pancreatic tumors. Material and Methods: 46 patients were prospectively evaluated by a combined MR imaging protocol including breath-hold T{sub 1}- and T{sub 2}-weighted pulse sequence, MRCP using a breath-hold 2D-RARE sequence, and breathhold gadolinium-enhanced dual-phase 3D-MR angiography. Results: All pancreatic tumors were detected by the combination of cross-sectional imaging and MRCP. In spite of the use of MRCP, definitive differentiation between pancreatic carcinoma and chronic pancreatitis was not possible in 3 (6.5%) out of 46 cases. High quality 3D-MR angiograms were obtained in 43 (93.5%) cases. In 6 (13%) patients 3D-MRA showed an aberrant right hepatic artery. The overall accuracy of MRI in assessing extrapancreatic tumor spread, lymph node metastases, liver metastases, and vascular involvement was 95.7%, 80.4%, 93.5%, and 89.1%, respectively. Conclusion: Due to its high accuracy the `all-in-one` MR protocol may become the most important modality after clinical examination and ultrasound in the diagnostic work-up for most patients with suspicion of pancreatic tumors. (orig.) [Deutsch] Ziel: Beurteilung der Wertigkeit eines `globalen` MR-Protokolls in der Diagnostik von Pankreastumoren. Material und Methode: 46 Patienten mit Verdacht auf Pankreaskarzinom wurden mit einem definierten Protokoll unter Einbeziehung von T{sub 1}- und T{sub 2}-gewichteten Sequenzen, einer 2D-RARE MRCP-Sequenz und einer konstrastverstaerkten 2-Phasen 3D-MRA untersucht. Ergebnisse: Alle Pankreastumoren wurden mit der Kombination von Schnittbild und MRCP nachgewiesen. Trotz des Einsatzes der MRCP gelang in 3 (6,5%) von 46 Faellen eine sichere Differenzierung zwischen Pankreaskarzinom und chronischer Pankreatitis nicht. Qualitativ hochwertige 3D-MR-Angiogramme wurden in 43 (93,5%) Faellen erzielt. In 6 (13%) Faellen wurde eine aberrierende, aus der A. mesenterica superior

  18. mTOR-inhibitor treatment of metastatic renal cell carcinoma: contribution of Choi and modified Choi criteria assessed in 2D or 3D to evaluate tumor response

    Lamuraglia, M. [Laboratoire d' Imagerie Biomedicale, Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Paris (France); Raslan, S.; Penna, R.R.; Wagner, M. [Groupe Hospitalier Pitie-Salpetriere, APHP UPMC, Service de Radiologie Polyvalente et Oncologique, Paris Cedex 13 (France); Elaidi, R.; Oudard, S. [APHP, Oncology Unit, Georges-Pompidou Hospital, Paris (France); Escudier, B. [Gustave-Roussy Institute, Medical Oncology Department, Villejuif (France); Slimane, K. [Novartis Pharma, Rueil-Malmaison (France); Lucidarme, O. [Groupe Hospitalier Pitie-Salpetriere, APHP UPMC, Service de Radiologie Polyvalente et Oncologique, Paris Cedex 13 (France); Laboratoire d' Imagerie Biomedicale, Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Paris (France)

    2016-01-15

    To determine whether 2D or 3D Choi and modified Choi (mChoi) criteria could assess the efficacy of everolimus against metastatic renal cell carcinoma (mRCC). RECIST-1.1, Choi, and mChoi criteria were applied retrospectively to analyse baseline and 2-month contrast-enhanced computed tomography (CECT) images in 48 patients with mRCC enrolled in the everolimus arm of the French randomized double-blind multicentre phase III trial comparing everolimus versus placebo (RECORD-1). The primary endpoint was centrally reviewed progression-free survival (PFS) calculated from the initial RECORD-1 analysis. Mean attenuation was determined for 2D target lesion regions of interest drawn on CECT sections whose largest diameters had been measured, and for the 3D whole target lesion. The median PFS was 5.5 months. The median PFS for everolimus responders defined using 3D mChoi criteria was significantly longer than for non-responders (7.6 versus 5.4 months, respectively), corresponding to a hazard ratio for progression of 0.45 (95 % CI: 0.22-0.92), with respective 1-year survival rates of 31 % and 9 %. No other 2D or 3D imaging criteria at 2 months identified patients who would benefit from everolimus. At 2 months, only 3D mChoi criteria were able to identify mRCC patients with a PFS benefit from everolimus. (orig.)

  19. mTOR-inhibitor treatment of metastatic renal cell carcinoma: contribution of Choi and modified Choi criteria assessed in 2D or 3D to evaluate tumor response

    To determine whether 2D or 3D Choi and modified Choi (mChoi) criteria could assess the efficacy of everolimus against metastatic renal cell carcinoma (mRCC). RECIST-1.1, Choi, and mChoi criteria were applied retrospectively to analyse baseline and 2-month contrast-enhanced computed tomography (CECT) images in 48 patients with mRCC enrolled in the everolimus arm of the French randomized double-blind multicentre phase III trial comparing everolimus versus placebo (RECORD-1). The primary endpoint was centrally reviewed progression-free survival (PFS) calculated from the initial RECORD-1 analysis. Mean attenuation was determined for 2D target lesion regions of interest drawn on CECT sections whose largest diameters had been measured, and for the 3D whole target lesion. The median PFS was 5.5 months. The median PFS for everolimus responders defined using 3D mChoi criteria was significantly longer than for non-responders (7.6 versus 5.4 months, respectively), corresponding to a hazard ratio for progression of 0.45 (95 % CI: 0.22-0.92), with respective 1-year survival rates of 31 % and 9 %. No other 2D or 3D imaging criteria at 2 months identified patients who would benefit from everolimus. At 2 months, only 3D mChoi criteria were able to identify mRCC patients with a PFS benefit from everolimus. (orig.)

  20. Irradiation of head-and-neck tumors with intensity modulated radiotherapy (IMRT). Comparison between two IMRT techniques with 3D conformal irradiation

    For 12 patients with inoperable head-neck carcinoma that were treated with 3D conformal irradiation techniques additional irradiation plans using IMRT were developed. It was shown that the IMRT techniques are superior to the 3D conformal technique. The new rapid arc technique is unclear with respect to the critical organs (parotid glands, spinal canal and mandibles) but is significantly advantageous for the other normal tissue with respect to conformity (steeper dose gradients) and thus radiation dose reduction. The resulting lower irradiation time and the reduced radiation exposure being important for the treatment economy and patients' comfort should favor the more planning intensive rapid arc technique.

  1. The effect of co-delivery of paclitaxel and curcumin by transferrin-targeted PEG-PE-based mixed micelles on resistant ovarian cancer in 3-D spheroids and in vivo tumors

    Sarisozen, Can; Abouzeid, Abraham H.; Torchilin, Vladimir P.

    2014-01-01

    Multicellular 3D cancer cell culture (spheroids) resemble to in vivo tumors in terms of shape, cell morphology, growth kinetics, gene expression and drug response. However, these characteristics cause very limited drug penetration into deeper parts of the spheroids. In this study, we used multi drug resistant (MDR) ovarian cancer cell spheroid and in vivo tumor models to evaluate the co-delivery of paclitaxel (PCL) and a potent NF-κB inhibitor curcumin (CUR). PCL and CUR were co-loaded into t...

  2. Open 3D Projects

    Felician ALECU

    2010-01-01

    Full Text Available Many professionals and 3D artists consider Blender as being the best open source solution for 3D computer graphics. The main features are related to modeling, rendering, shading, imaging, compositing, animation, physics and particles and realtime 3D/game creation.

  3. 3d-3d correspondence revisited

    Chung, Hee-Joong; Dimofte, Tudor; Gukov, Sergei; Sułkowski, Piotr

    2016-04-01

    In fivebrane compactifications on 3-manifolds, we point out the importance of all flat connections in the proper definition of the effective 3d {N}=2 theory. The Lagrangians of some theories with the desired properties can be constructed with the help of homological knot invariants that categorify colored Jones polynomials. Higgsing the full 3d theories constructed this way recovers theories found previously by Dimofte-Gaiotto-Gukov. We also consider the cutting and gluing of 3-manifolds along smooth boundaries and the role played by all flat connections in this operation.

  4. Use of 3-D HD auxiliary monitor by bedside assistant results in shorter console-time and ischemia-time in robot assisted laparoscopic partial tumor-nephrectomy

    Alamyar, M.; Bouma, H; ; Goossens, W.J.H.; Wieringa, F.P.; Kroon, B.K.; Eendebak, P.T.; Wijburg, C.J.; Smits, G.A.H.J.

    2014-01-01

    Recently, we have shown that connecting live three-dimensional (3D) monitors to all three available Da Vinci® robot (Intuitive) generations improved the impression of shared perception for the whole surgical team. Standardized dry lab experiments revealed that delicate teamwork was faster (up to 40%

  5. IZDELAVA TISKALNIKA 3D

    Brdnik, Lovro

    2015-01-01

    Diplomsko delo analizira trenutno stanje 3D tiskalnikov na trgu. Prikazan je razvoj in principi delovanja 3D tiskalnikov. Predstavljeni so tipi 3D tiskalnikov, njihove prednosti in slabosti. Podrobneje je predstavljena zgradba in delovanje koračnih motorjev. Opravljene so meritve koračnih motorjev. Opisana je programska oprema za rokovanje s 3D tiskalniki in komponente, ki jih potrebujemo za izdelavo. Diploma se oklepa vprašanja, ali je izdelava 3D tiskalnika bolj ekonomična kot pa naložba v ...

  6. 3D and Education

    Meulien Ohlmann, Odile

    2013-02-01

    Today the industry offers a chain of 3D products. Learning to "read" and to "create in 3D" becomes an issue of education of primary importance. 25 years professional experience in France, the United States and Germany, Odile Meulien set up a personal method of initiation to 3D creation that entails the spatial/temporal experience of the holographic visual. She will present some different tools and techniques used for this learning, their advantages and disadvantages, programs and issues of educational policies, constraints and expectations related to the development of new techniques for 3D imaging. Although the creation of display holograms is very much reduced compared to the creation of the 90ies, the holographic concept is spreading in all scientific, social, and artistic activities of our present time. She will also raise many questions: What means 3D? Is it communication? Is it perception? How the seeing and none seeing is interferes? What else has to be taken in consideration to communicate in 3D? How to handle the non visible relations of moving objects with subjects? Does this transform our model of exchange with others? What kind of interaction this has with our everyday life? Then come more practical questions: How to learn creating 3D visualization, to learn 3D grammar, 3D language, 3D thinking? What for? At what level? In which matter? for whom?

  7. Changes in global gene expression associated with 3D structure of tumors: an ex vivo matrix-free mesothelioma spheroid model.

    Kim, Heungnam; Phung, Yen; Ho, Mitchell

    2012-01-01

    Tumor microenvironments present significant barriers to anti-tumor agents. Molecules involved in multicellular tumor microenvironments, however, are difficult to study ex vivo. Here, we generated a matrix-free tumor spheroid model using the NCI-H226 mesothelioma cell line and compared the gene expression profiles of spheroids and monolayers using microarray analysis. Microarray analysis revealed that 142 probe sets were differentially expressed between tumor spheroids and monolayers. Gene ontology analysis revealed that upregulated genes were primarily related to immune response, wound response, lymphocyte stimulation and response to cytokine stimulation, whereas downregulated genes were primarily associated with apoptosis. Among the 142 genes, 27 are located in the membrane and related to biologic processes of cellular movement, cell-to-cell signaling, cellular growth and proliferation and morphology. Western blot analysis validated elevation of MMP2, BAFF/BLyS/TNFSF13B, RANTES/CCL5 and TNFAIP6/TSG-6 protein expression in spheroids as compared to monolayers. Thus, we have reported the first large scale comparison of the transcriptional profiles using an ex vivo matrix-free spheroid model to identify genes specific to the three-dimensional biological structure of tumors. The method described here can be used for gene expression profiling of tumors other than mesothelioma. PMID:22737246

  8. Changes in global gene expression associated with 3D structure of tumors: an ex vivo matrix-free mesothelioma spheroid model.

    Heungnam Kim

    Full Text Available Tumor microenvironments present significant barriers to anti-tumor agents. Molecules involved in multicellular tumor microenvironments, however, are difficult to study ex vivo. Here, we generated a matrix-free tumor spheroid model using the NCI-H226 mesothelioma cell line and compared the gene expression profiles of spheroids and monolayers using microarray analysis. Microarray analysis revealed that 142 probe sets were differentially expressed between tumor spheroids and monolayers. Gene ontology analysis revealed that upregulated genes were primarily related to immune response, wound response, lymphocyte stimulation and response to cytokine stimulation, whereas downregulated genes were primarily associated with apoptosis. Among the 142 genes, 27 are located in the membrane and related to biologic processes of cellular movement, cell-to-cell signaling, cellular growth and proliferation and morphology. Western blot analysis validated elevation of MMP2, BAFF/BLyS/TNFSF13B, RANTES/CCL5 and TNFAIP6/TSG-6 protein expression in spheroids as compared to monolayers. Thus, we have reported the first large scale comparison of the transcriptional profiles using an ex vivo matrix-free spheroid model to identify genes specific to the three-dimensional biological structure of tumors. The method described here can be used for gene expression profiling of tumors other than mesothelioma.

  9. AP-PA field orientation followed by IMRT reduces lung exposure in comparison to conventional 3D conformal and sole IMRT in centrally located lung tumors

    Soyfer Viacheslav; Meir Yaron; Corn Benjamin W; Schifter Dan; Gez Eliahu; Tempelhoff Haim; Shtraus Natan

    2012-01-01

    Abstract Little attention has been paid to the fact that intensity modulated radiation therapy (IMRT) techniques do not easily enable treatment with opposed beams. Three treatment plans (3 D conformal, IMRT, and combined (anterior-posterior-posterio-anterior (AP-PA) + IMRT) of 7 patients with centrally-located lung cancer were compared for exposure of lung, spinal cord and esophagus. Combined IMRT and AP-PA techniques offer better lung tissue sparing compared to plans predicated solely on IMR...

  10. The impact of including spatially longitudinal heterogeneities of vessel oxygen content and vascular fraction in 3D tumor oxygenation models on predicted radiation sensitivity

    Lagerlöf, Jakob H., E-mail: Jakob@radfys.gu.se [Department of Radiation Physics, Göteborg University, Göteborg 41345 (Sweden); Kindblom, Jon [Department of Oncology, Sahlgrenska University Hospital, Göteborg 41345 (Sweden); Bernhardt, Peter [Department of Radiation Physics, Göteborg University, Göteborg 41345, Sweden and Department of Nuclear Medicine, Sahlgrenska University Hospital, Göteborg 41345 (Sweden)

    2014-04-15

    Purpose: Oxygen distribution models have been used to analyze the influences of oxygen tensions on tissue response after radiotherapy. These distributions are often generated assuming constant oxygen tension in the blood vessels. However, as red blood cells progress through the vessels, oxygen is continuously released into the plasma and the surrounding tissue, resulting in longitudinally varying oxygen levels in the blood vessels. In the present study, the authors investigated whether a tumor oxygenation model that incorporated longitudinally varying oxygen levels would provide different predictions of necrotic fractions and radiosensitivity compared to commonly used models with a constant oxygen pressure. Methods: Our models simulated oxygen diffusion based on a Green's function approach and oxygen consumption according to the Michaelis-Menten equation. The authors constructed tumor models with different vascular fractions (VFs), from which they generated depth oxygenation curves and a look-up table of oxygen pressure gradients. The authors evaluated models of spherical tumors of various sizes, from 1 to 10{sup 4} mg. The authors compared the results from a model with constant vessel oxygen (CVO) pressure to those from models with longitudinal variations in oxygen saturation and either a constant VF (CVF) or variable VF (VVF) within the tumor tissue. The authors monitored the necrotic fractions, defined as tumor regions with an oxygen pressure below 1 mmHg. Tumor radiation sensitivity was expressed as D{sub 99,} the homogeneous radiation dose required for a tumor control probability of 0.99. Results: In the CVO saturation model, no necrosis was observed, and decreasing the VF could only decrease the D{sub 99} by up to 10%. Furthermore, the D{sub 99} vs VF dependence was similar for different tumor masses. Compared to the CVO model, the extended CVF and VVF models provided clearly different results, including pronounced effects of VF and tumor size on the

  11. Tumor-penetrating peptide fused EGFR single-domain antibody enhances cancer drug penetration into 3D multicellular spheroids and facilitates effective gastric cancer therapy

    Sha, Huizi; Zou, Zhengyun; Xin, Kai; Bian, Xinyu; Cai, Xueting; Lu, Wuguang; Chen, Jiao; Chen, Gang; Huang, Leaf; Blair, Andrew M.; Cao, Peng; Liu, Baorui

    2016-01-01

    Human tumors, including gastric cancer, frequently express high levels of epidermal growth factor receptors (EGFRs), which are associated with a poor prognosis. Targeted delivery of anticancer drugs to cancerous tissues shows potential in sparing unaffected tissues. However, it has been a major challenge for drug penetration in solid tumor tissues due to the complicated tumor microenvironment. We have constructed a recombinant protein named anti-EGFR-iRGD consisting of an anti-EGFR VHH (the variable domain from the heavy chain of the antibody) fused to iRGD, a tumor-specific binding peptide with high permeability. Anti-EGFR-iRGD, which targets EGFR and αvβ3, spreads extensively throughout both the multicellular spheroids and the tumor mass. The recombinant protein anti-EGFR-iRGD also exhibited antitumor activity in tumor cell lines, multicellular spheroids, and mice. Moreover, anti-EGFR-iRGD could improve anticancer drugs, such as doxorubicin (DOX), bevacizumab, nanoparticle permeability and efficacy in multicellular spheroids. This study draws attention to the importance of iRGD peptide in the therapeutic approach of anti-EGFR-iRGD. As a consequence, anti-EGFR-iRGD could be a drug candidate for cancer treatment and a useful adjunct of other anticancer drugs. PMID:25553823

  12. Prospective study on the dose distribution to the acoustic structures during postoperative 3D conformal radiotherapy for parotid tumors. Dosimetric and audiometric aspects

    To analyze dose distribution in the hearing organ and to evaluate the dose effect on the hearing thresholds in patients treated with post-parotidectomy 3-dimensional conformal radiotherapy (3D-CRT). A total of 17 patients received post-parotidectomy 3D-CRT (median dose: 63 Gy). The audiometric evaluation comprised pure tone audiometry and tympanometry performed before radiotherapy (RT) and 3, 6, and 24 months after RT. The ear structures were delineated on planning computer tomography scans. Mean and maximum doses were calculated and dose-volume histograms were plotted. Before RT, the median baseline audiometric thresholds were normal. At 3 months post-RT, 3 patients were diagnosed as having middle ear underpressure and/or effusion that resolved completely by 6 months. During 2-year follow-up, none of the ears showed perceptive hearing loss at speech frequencies. The mean doses at ipsilateral external auditory canal, mastoids cells, tympanic case, Eustachian tube, semicircular canals, and cochlea were 44.8 Gy, 39.0 Gy, 30.9 Gy, 33.0 Gy, 19.6 Gy, and 19.2 Gy, respectively. The doses to the contralateral ear were negligible, except for the Eustachian tube (up to 28.2 Gy). Post-parotidectomy 3D-CRT is associated with relatively low doses to the ear and the surrounding structures. Post-RT audiometry did not show any permanent (neither conductive nor perceptive) hearing impairment. Only in 3 patients were there signs of transient unilateral dysfunction of the Eustachian tube observed during the first few months after RT. Longer follow-up and larger patient series are warranted to confirm these preliminary findings. (orig.)

  13. Prospective study on the dose distribution to the acoustic structures during postoperative 3D conformal radiotherapy for parotid tumors. Dosimetric and audiometric aspects

    Jereczek-Fossa, Barbara A. [European Inst. of Oncology, Milan (Italy). Division of Radiotherapy; Milan Univ. (Italy). Faculty of Medicine; Rondi, Elena [European Inst. of Oncology, Milan (Italy). Division of Medical Physics; Zarowski, Andrzej [Univ. Dept. of Otolaryngology, Head and Neck Surgery, St. Augustinus Hospital, Antwerp (BE)] (and others)

    2011-06-15

    To analyze dose distribution in the hearing organ and to evaluate the dose effect on the hearing thresholds in patients treated with post-parotidectomy 3-dimensional conformal radiotherapy (3D-CRT). A total of 17 patients received post-parotidectomy 3D-CRT (median dose: 63 Gy). The audiometric evaluation comprised pure tone audiometry and tympanometry performed before radiotherapy (RT) and 3, 6, and 24 months after RT. The ear structures were delineated on planning computer tomography scans. Mean and maximum doses were calculated and dose-volume histograms were plotted. Before RT, the median baseline audiometric thresholds were normal. At 3 months post-RT, 3 patients were diagnosed as having middle ear underpressure and/or effusion that resolved completely by 6 months. During 2-year follow-up, none of the ears showed perceptive hearing loss at speech frequencies. The mean doses at ipsilateral external auditory canal, mastoids cells, tympanic case, Eustachian tube, semicircular canals, and cochlea were 44.8 Gy, 39.0 Gy, 30.9 Gy, 33.0 Gy, 19.6 Gy, and 19.2 Gy, respectively. The doses to the contralateral ear were negligible, except for the Eustachian tube (up to 28.2 Gy). Post-parotidectomy 3D-CRT is associated with relatively low doses to the ear and the surrounding structures. Post-RT audiometry did not show any permanent (neither conductive nor perceptive) hearing impairment. Only in 3 patients were there signs of transient unilateral dysfunction of the Eustachian tube observed during the first few months after RT. Longer follow-up and larger patient series are warranted to confirm these preliminary findings. (orig.)

  14. Optical laser scanning of a leucodye micelle gel: preliminary results of a 3D dose verification of an IMRT treatment for a brain tumor

    Vandecasteele, J.; De Deene, Y.

    2013-06-01

    In the present study an in-house developed leucodye micelle gel was used in combination with an in-house developed optical laser scanner for the 3D dose verification of an IMRT treatment of a pituitary adenoma. In an initial prospective study, a gel measured depth dose distribution of a square 6 MV photon beam was compared with an ion chamber measurement. In a second experiment, the gel and scanner were used to verify a clinical dose distribution on a recently installed linear accelerator. The calibration procedure is identified as the major source of dose deviations.

  15. Corneal avascularity is due to soluble VEGF receptor-1.

    Ambati, Balamurali K; Nozaki, Miho; Singh, Nirbhai; Takeda, Atsunobu; Jani, Pooja D; Suthar, Tushar; Albuquerque, Romulo J C; Richter, Elizabeth; Sakurai, Eiji; Newcomb, Michael T; Kleinman, Mark E; Caldwell, Ruth B; Lin, Qing; Ogura, Yuichiro; Orecchia, Angela; Samuelson, Don A; Agnew, Dalen W; St Leger, Judy; Green, W Richard; Mahasreshti, Parameshwar J; Curiel, David T; Kwan, Donna; Marsh, Helene; Ikeda, Sakae; Leiper, Lucy J; Collinson, J Martin; Bogdanovich, Sasha; Khurana, Tejvir S; Shibuya, Masabumi; Baldwin, Megan E; Ferrara, Napoleone; Gerber, Hans-Peter; De Falco, Sandro; Witta, Jassir; Baffi, Judit Z; Raisler, Brian J; Ambati, Jayakrishna

    2006-10-26

    Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea. PMID:17051153

  16. 3D virtuel udstilling

    Tournay, Bruno; Rüdiger, Bjarne

    2006-01-01

    3d digital model af Arkitektskolens gård med virtuel udstilling af afgangsprojekter fra afgangen sommer 2006. 10 s.......3d digital model af Arkitektskolens gård med virtuel udstilling af afgangsprojekter fra afgangen sommer 2006. 10 s....

  17. Avascular necrosis associated with nailing of femoral neck fracture

    Two patients with femoral neck fractures, one displaced and one undisplaced, are presented. Preoperative intravital staining with tetracycline and Tc-MDP scintimetry both showed intact femoral head circulation while Tc-MDP-scintimetry 1 week after operation showed pronounced circulatory deficiency. SR85-scintimetry performed at the same time was inconclusive. Segmental collapse was observed radiographically, 8 and 12 months postoperatively. The major vascular injury resulting in avascularity most probably occured during the procedure of osteosynthesis, and Tc-MDP-scintimetry was found suitable for early postoperative recognition of avascular necrosis in both fractures. (author)

  18. Underwater 3D filming

    Roberto Rinaldi

    2014-12-01

    Full Text Available After an experimental phase of many years, 3D filming is now effective and successful. Improvements are still possible, but the film industry achieved memorable success on 3D movie’s box offices due to the overall quality of its products. Special environments such as space (“Gravity” and the underwater realm look perfect to be reproduced in 3D. “Filming in space” was possible in “Gravity” using special effects and computer graphic. The underwater realm is still difficult to be handled. Underwater filming in 3D was not that easy and effective as filming in 2D, since not long ago. After almost 3 years of research, a French, Austrian and Italian team realized a perfect tool to film underwater, in 3D, without any constrains. This allows filmmakers to bring the audience deep inside an environment where they most probably will never have the chance to be.

  19. Blender 3D cookbook

    Valenza, Enrico

    2015-01-01

    This book is aimed at the professionals that already have good 3D CGI experience with commercial packages and have now decided to try the open source Blender and want to experiment with something more complex than the average tutorials on the web. However, it's also aimed at the intermediate Blender users who simply want to go some steps further.It's taken for granted that you already know how to move inside the Blender interface, that you already have 3D modeling knowledge, and also that of basic 3D modeling and rendering concepts, for example, edge-loops, n-gons, or samples. In any case, it'

  20. Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells

    Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and PKD by curcumin causes stabilization of the tumor suppressor p53. It has been shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun steady state levels in HeLa cells. The aim of this work was to search for new CSN kinase inhibitors analogue to curcumin and emodin by means of an in silico screening method. Here we present a novel method to identify efficient inhibitors of CSN-associated kinases. Using curcumin and emodin as lead structures an in silico screening with our in-house database containing more than 106 structures was carried out. Thirty-five compounds were identified and further evaluated by the Lipinski's rule-of-five. Two groups of compounds can be clearly discriminated according to their structures: the curcumin-group and the emodin-group. The compounds were evaluated in in vitro kinase assays and in cell culture experiments. The data revealed 3 compounds of the curcumin-group (e.g. piceatannol) and 4 of the emodin-group (e.g. anthrachinone) as potent inhibitors of CSN-associated kinases. Identified agents increased p53 levels and induced apoptosis in tumor cells as determined by annexin V-FITC binding, DNA fragmentation and caspase activity assays. Our data demonstrate that the new in silico screening method is highly efficient for identifying potential anti-tumor drugs

  1. Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model.

    Kuryk, Lukasz; Haavisto, Elina; Garofalo, Mariangela; Capasso, Cristian; Hirvinen, Mari; Pesonen, Sari; Ranki, Tuuli; Vassilev, Lotta; Cerullo, Vincenzo

    2016-10-15

    Malignant mesothelioma (MM) is a rare cancer type caused mainly by asbestos exposure. The median overall survival time of a mesothelioma cancer patient is less than 1-year from diagnosis. Currently there are no curative treatment modalities for malignant mesothelioma, however treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase life expectancy. Pemetrexed-Cisplatin is the only standard of care (SoC) chemotherapy for malignant mesothelioma, but the median PFS/OS (progression-free survival/overall survival) from the initiation of treatment is only up to 12 months. Therefore, new treatment strategies against malignant mesothelioma are in high demand. ONCOS-102 is a dual targeting, chimeric oncolytic adenovirus, coding for human GM-CSF. The safety and immune activating properties of ONCOS-102 have already been assessed in phase 1 study (NCT01598129). In this preclinical study, we evaluated the antineoplastic activity of combination treatment with SoC chemotherapy (Pemetrexed, Cisplatin, Carboplatin) and ONCOS-102 in xenograft BALB/c model of human malignant mesothelioma. We demonstrated that ONCOS-102 is able to induce immunogenic cell death of human mesothelioma cell lines in vitro and showed anti-tumor activity in the treatment of refractory H226 malignant pleural mesothelioma (MPM) xenograft model. While chemotherapy alone showed no anti-tumor activity in the mesothelioma mouse model, ONCOS-102 was able to slow down tumor growth. Interestingly, a synergistic anti-tumor effect was seen when ONCOS-102 was combined with chemotherapy regimens. These findings give a rationale for the clinical testing of ONCOS-102 in combination with first-line chemotherapy in patients suffering from malignant mesothelioma. PMID:27287512

  2. 3D Digital Modelling

    Hundebøl, Jesper

    wave of new building information modelling tools demands further investigation, not least because of industry representatives' somewhat coarse parlance: Now the word is spreading -3D digital modelling is nothing less than a revolution, a shift of paradigm, a new alphabet... Research qeustions. Based...... on empirical probes (interviews, observations, written inscriptions) within the Danish construction industry this paper explores the organizational and managerial dynamics of 3D Digital Modelling. The paper intends to - Illustrate how the network of (non-)human actors engaged in the promotion (and arrest) of 3......D Modelling (in Denmark) stabilizes - Examine how 3D Modelling manifests itself in the early design phases of a construction project with a view to discuss the effects hereof for i.a. the management of the building process. Structure. The paper introduces a few, basic methodological concepts...

  3. Professional Papervision3D

    Lively, Michael

    2010-01-01

    Professional Papervision3D describes how Papervision3D works and how real world applications are built, with a clear look at essential topics such as building websites and games, creating virtual tours, and Adobe's Flash 10. Readers learn important techniques through hands-on applications, and build on those skills as the book progresses. The companion website contains all code examples, video step-by-step explanations, and a collada repository.

  4. Endorectal 3D T2-weighted 1 mm-slice thickness MRI for prostate cancer staging at 1.5 Tesla: Should we reconsider the indirects signs of extracapsular extension according to the D’Amico tumor risk criteria?

    Purpose: To evaluate the accuracy of a 3D-endorectal 1 mm-thick slices MRI acquisition for local staging of low, intermediate and high D’Amico risk prostate cancer (PCa). Materials and methods: 178 consecutive patients underwent a multiparametric MRI protocol prior to radical prostatectomy (RP). T2W images were acquired with the 3D sampling perfection with application optimized contrasts using different flip angle evolutions (SPACE) sequence (5 mn acquisition time). Direct and indirect MRI signs of extracapsular extension (ECE) were evaluated to predict the pT stage. The likelihood of SVI (seminal vesicle invasion) was also assessed. Results: Histology showed ECE and SVI in 38 (21%) and 12 (7%) cases, respectively. MRI sensitivity and specificity to detect ECE were 55 and 96% if direct signs of ECE were used and 84 and 89% (p < 0.05), if both direct and indirect signs were combined. D’Amico criteria did not influence MRI performance. Sensitivity and specificity for SVI detection were 83% and 99%. Conclusions: 3D data sets acquired with the SPACE sequence provides a high accuracy for local staging of prostate cancer. The use of indirect signs of ECE may be recommended in low D’Amico risk tumors to optimise patient selection for active surveillance or focal therapy.

  5. Specific CT 3D rendering of the treatment zone after Irreversible Electroporation (IRE) in a pig liver model: the “Chebyshev Center Concept” to define the maximum treatable tumor size

    Size and shape of the treatment zone after Irreversible electroporation (IRE) can be difficult to depict due to the use of multiple applicators with complex spatial configuration. Exact geometrical definition of the treatment zone, however, is mandatory for acute treatment control since incomplete tumor coverage results in limited oncological outcome. In this study, the “Chebyshev Center Concept” was introduced for CT 3d rendering to assess size and position of the maximum treatable tumor at a specific safety margin. In seven pig livers, three different IRE protocols were applied to create treatment zones of different size and shape: Protocol 1 (n = 5 IREs), Protocol 2 (n = 5 IREs), and Protocol 3 (n = 5 IREs). Contrast-enhanced CT was used to assess the treatment zones. Technique A consisted of a semi-automated software prototype for CT 3d rendering with the “Chebyshev Center Concept” implemented (the “Chebyshev Center” is the center of the largest inscribed sphere within the treatment zone) with automated definition of parameters for size, shape and position. Technique B consisted of standard CT 3d analysis with manual definition of the same parameters but position. For Protocol 1 and 2, short diameter of the treatment zone and diameter of the largest inscribed sphere within the treatment zone were not significantly different between Technique A and B. For Protocol 3, short diameter of the treatment zone and diameter of the largest inscribed sphere within the treatment zone were significantly smaller for Technique A compared with Technique B (41.1 ± 13.1 mm versus 53.8 ± 1.1 mm and 39.0 ± 8.4 mm versus 53.8 ± 1.1 mm; p < 0.05 and p < 0.01). For Protocol 1, 2 and 3, sphericity of the treatment zone was significantly larger for Technique A compared with B. Regarding size and shape of the treatment zone after IRE, CT 3d rendering with the “Chebyshev Center Concept” implemented provides significantly different results compared with standard CT 3d

  6. Low-cost photodynamic therapy devices for global health settings: Characterization of battery-powered LED performance and smartphone imaging in 3D tumor models

    Hempstead, Joshua; Jones, Dustin P.; Ziouche, Abdelali; Cramer, Gwendolyn M.; Rizvi, Imran; Arnason, Stephen; Hasan, Tayyaba; Celli, Jonathan P.

    2015-05-01

    A lack of access to effective cancer therapeutics in resource-limited settings is implicated in global cancer health disparities between developed and developing countries. Photodynamic therapy (PDT) is a light-based treatment modality that has exhibited safety and efficacy in the clinic using wavelengths and irradiances achievable with light-emitting diodes (LEDs) operated on battery power. Here we assess low-cost enabling technology to extend the clinical benefit of PDT to regions with little or no access to electricity or medical infrastructure. We demonstrate the efficacy of a device based on a 635 nm high-output LED powered by three AA disposable alkaline batteries, to achieve strong cytotoxic response in monolayer and 3D cultures of A431 squamous carcinoma cells following photosensitization by administering aminolevulinic acid (ALA) to induce the accumulation of protoporphyrin IX (PpIX). Here we characterize challenges of battery-operated device performance, including battery drain and voltage stability specifically over relevant PDT dose parameters. Further motivated by the well-established capacity of PDT photosensitizers to serve as tumour-selective fluorescence contrast agents, we demonstrate the capability of a consumer smartphone with low-cost add-ons to measure concentration-dependent PpIX fluorescence. This study lays the groundwork for the on-going development of image-guided ALA-PDT treatment technologies for global health applications.

  7. Design, synthesis, anti-tumor activity, and molecular modeling of quinazoline and pyrido[2,3-d]pyrimidine derivatives targeting epidermal growth factor receptor.

    Hou, Ju; Wan, Shanhe; Wang, Guangfa; Zhang, Tingting; Li, Zhonghuang; Tian, Yuanxin; Yu, Yonghuan; Wu, Xiaoyun; Zhang, Jiajie

    2016-08-01

    Three series of novel quinazoline and pyrido[2,3-d]pyrimidine derivatives were designed, synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase and a panel of five human cancer cell lines (MCF-7, A549, BT-474, SK-BR-3, and MDA-MB-231). Bioassay results indicated that five of these prepared compounds (12c-12e and 13c-13d) exhibited remarkably higher inhibitory activities against EGFR and SK-BR-3 cell line. Compounds 12c and 12e displayed the most potent EGFR inhibitory activity (IC50 = 2.97 nM and 3.58 nM, respectively) and good anti-proliferative effect against SK-BR-3 cell with the IC50 values of 3.10 μM and 5.87 μM, respectively. Furthermore, molecular docking and molecular dynamics simulation studies verified that compound 12c and 12e shared similar binding pattern with gefitinib in the binding pocket of EGFR. MM-GBSA binding free energy revealed that the compound 12c and 12e have almost the same inhibitory activity against EGFR as gefitinib, and that the dominating effect of van der Waals interactions drives the binding process. PMID:27132165

  8. Real-time measurement of hyperpolarized lactate production and efflux as a biomarker of tumor aggressiveness in an MR compatible 3D cell culture bioreactor.

    Sriram, Renuka; Van Criekinge, Mark; Hansen, Ailin; Wang, Zhen J; Vigneron, Daniel B; Wilson, David M; Keshari, Kayvan R; Kurhanewicz, John

    2015-09-01

    We have developed a 3D cell/tissue culture bioreactor compatible with hyperpolarized (HP) (13)C MR and interrogated HP [1-(13)C]lactate production and efflux in human renal cell carcinoma (RCC) cells. This platform is capable of resolving intracellular and extracellular HP lactate pools, allowing the kinetic measurement of lactate production and efflux in the context of cancer aggressiveness and response to therapy. HP (13)C MR studies were performed on three immortalized human renal cell lines: HK2, a normal renal proximal tubule cell line from which a majority of RCCs arise, UMRC6, a cell line derived from a localized RCC, and UOK262, an aggressive and metastatic RCC. The intra- (Lacin ) and extracellular (Lacex ) HP lactate signals were robustly resolved in dynamic (13)C spectra of the cell lines due to a very small but reproducible chemical shift difference (0.031 ± 0.0005 ppm). Following HP [1-(13)C]pyruvate delivery, the ratio of HP Lacin /Lacex was significantly lower for UOK262 cells compared with both UMRC6 and HK2 cells due to a significant (p culture bioreactor to study not only cellular metabolism but also transport. Additionally, this platform offers a sophisticated way to follow therapeutic interventions and screen novel therapies that target lactate export. PMID:26202449

  9. 3D Spectroscopic Instrumentation

    Bershady, Matthew A

    2009-01-01

    In this Chapter we review the challenges of, and opportunities for, 3D spectroscopy, and how these have lead to new and different approaches to sampling astronomical information. We describe and categorize existing instruments on 4m and 10m telescopes. Our primary focus is on grating-dispersed spectrographs. We discuss how to optimize dispersive elements, such as VPH gratings, to achieve adequate spectral resolution, high throughput, and efficient data packing to maximize spatial sampling for 3D spectroscopy. We review and compare the various coupling methods that make these spectrographs ``3D,'' including fibers, lenslets, slicers, and filtered multi-slits. We also describe Fabry-Perot and spatial-heterodyne interferometers, pointing out their advantages as field-widened systems relative to conventional, grating-dispersed spectrographs. We explore the parameter space all these instruments sample, highlighting regimes open for exploitation. Present instruments provide a foil for future development. We give an...

  10. 3D Projection Installations

    Halskov, Kim; Johansen, Stine Liv; Bach Mikkelsen, Michelle

    2014-01-01

    Three-dimensional projection installations are particular kinds of augmented spaces in which a digital 3-D model is projected onto a physical three-dimensional object, thereby fusing the digital content and the physical object. Based on interaction design research and media studies, this article...... contributes to the understanding of the distinctive characteristics of such a new medium, and identifies three strategies for designing 3-D projection installations: establishing space; interplay between the digital and the physical; and transformation of materiality. The principal empirical case, From...... Fingerplan to Loop City, is a 3-D projection installation presenting the history and future of city planning for the Copenhagen area in Denmark. The installation was presented as part of the 12th Architecture Biennale in Venice in 2010....

  11. Dosimetric impact of inter-observer variability for 3D conformal radiotherapy and volumetric modulated arc therapy: the rectal tumor target definition case

    To assess the dosimetric effect induced by inter-observer variability in target definition for 3D-conformal RT (3DCRT) and volumetric modulated arc therapy by RapidArc (RA) techniques for rectal cancer treatment. Ten patients with rectal cancer subjected to neo-adjuvant RT were randomly selected from the internal database. Four radiation oncologists independently contoured the clinical target volume (CTV) in blind mode. Planning target volume (PTV) was defined as CTV + 7 mm in the three directions. Afterwards, shared guidelines between radiation oncologists were introduced to give general criteria for the contouring of rectal target and the four radiation oncologists defined new CTV following the guidelines. For each patient, six intersections (I) and unions (U) volumes were calculated coupling the contours of the various oncologists. This was repeated for the contours drawn after the guidelines. Agreement Index (AI = I/U) was calculated pre and post guidelines. Two RT plans (one with 3DCRT technique using 3–4 fields and one with RA using a single modulated arc) were optimized on each radiation oncologist’s PTV. For each plan the PTV volume receiving at least 95% of the prescribed dose (PTV V95%) was calculated for both target and non-target PTVs. The inter-operator AI pre-guidelines was 0.57 and was increased up to 0.69 post-guidelines. The maximum volume difference between the various CTV couples, drawn for each patient, passed from 380 ± 147 cm3 to 137 ± 83 cm3 after the introduction of guidelines. The mean percentage for the non-target PTV V95% was 93.7 ± 9.2% before and 96.6 ± 4.9%after the introduction of guidelines for the 3DCRT, for RA the increase was more relevant, passing from 86.5 ± 13.8% (pre) to 94.5 ± 7.5% (post). The OARs were maximally spared with VMAT technique while the variability between pre and post guidelines was not relevant in both techniques. The contouring inter-observer variability has dosimetric effects in the PTV coverage

  12. Herramientas SIG 3D

    Francisco R. Feito Higueruela

    2010-04-01

    Full Text Available Applications of Geographical Information Systems on several Archeology fields have been increasing during the last years. Recent avances in these technologies make possible to work with more realistic 3D models. In this paper we introduce a new paradigm for this system, the GIS Thetrahedron, in which we define the fundamental elements of GIS, in order to provide a better understanding of their capabilities. At the same time the basic 3D characteristics of some comercial and open source software are described, as well as the application to some samples on archeological researchs

  13. Bootstrapping 3D fermions

    Iliesiu, Luca; Kos, Filip; Poland, David; Pufu, Silviu S.; Simmons-Duffin, David; Yacoby, Ran

    2016-03-01

    We study the conformal bootstrap for a 4-point function of fermions in 3D. We first introduce an embedding formalism for 3D spinors and compute the conformal blocks appearing in fermion 4-point functions. Using these results, we find general bounds on the dimensions of operators appearing in the ψ × ψ OPE, and also on the central charge C T . We observe features in our bounds that coincide with scaling dimensions in the GrossNeveu models at large N . We also speculate that other features could coincide with a fermionic CFT containing no relevant scalar operators.

  14. TOWARDS: 3D INTERNET

    Ms. Swapnali R. Ghadge

    2013-01-01

    In today’s ever-shifting media landscape, it can be a complex task to find effective ways to reach your desired audience. As traditional media such as television continue to lose audience share, one venue in particular stands out for its ability to attract highly motivated audiences and for its tremendous growth potential the 3D Internet. The concept of '3D Internet' has recently come into the spotlight in the R&D arena, catching the attention of many people, and leading to a lot o...

  15. 3D Dental Scanner

    Kotek, L.

    2015-01-01

    This paper is about 3D scan of plaster dental casts. The main aim of the work is a hardware and software proposition of 3D scan system for scanning of dental casts. There were used camera, projector and rotate table for this scanning system. Surface triangulation was used, taking benefits of projections of structured light on object, which is being scanned. The rotate table is controlled by PC. The camera, projector and rotate table are synchronized by PC. Controlling of stepper motor is prov...

  16. Interaktiv 3D design

    Villaume, René Domine; Ørstrup, Finn Rude

    2002-01-01

    Projektet undersøger potentialet for interaktiv 3D design via Internettet. Arkitekt Jørn Utzons projekt til Espansiva blev udviklet som et byggesystem med det mål, at kunne skabe mangfoldige planmuligheder og mangfoldige facade- og rumudformninger. Systemets bygningskomponenter er digitaliseret som...... 3D elementer og gjort tilgængelige. Via Internettet er det nu muligt at sammenstille og afprøve en uendelig  række bygningstyper som  systemet blev tænkt og udviklet til....

  17. 3D Harmonic Echocardiography:

    M.M. Voormolen

    2007-01-01

    textabstractThree dimensional (3D) echocardiography has recently developed from an experimental technique in the ’90 towards an imaging modality for the daily clinical practice. This dissertation describes the considerations, implementation, validation and clinical application of a unique

  18. Tangible 3D Modelling

    Hejlesen, Aske K.; Ovesen, Nis

    2012-01-01

    This paper presents an experimental approach to teaching 3D modelling techniques in an Industrial Design programme. The approach includes the use of tangible free form models as tools for improving the overall learning. The paper is based on lecturer and student experiences obtained through...

  19. Shaping 3-D boxes

    Stenholt, Rasmus; Madsen, Claus B.

    2011-01-01

    Enabling users to shape 3-D boxes in immersive virtual environments is a non-trivial problem. In this paper, a new family of techniques for creating rectangular boxes of arbitrary position, orientation, and size is presented and evaluated. These new techniques are based solely on position data...

  20. Systematic review of the effect of radiation dose on tumor control and morbidity in the treatment of prostate cancer by 3D-CRT

    Purpose: A higher radiation dose is believed to result in a larger probability of tumor control and a higher risk of side effects. To make an evidence-based choice of dose, the relation between dose and outcome needs to be known. This study focuses on the dose-response relation for prostate cancer. Methods and Materials: A systematic review was carried out on the literature from 1990 to 2003. From the selected studies, the radiation dose, the associated 5-year survival, 5-year bNED (biochemical no evidence of disease), acute and late gastrointestinal (GI) and genitourinary (GU) morbidity Grade 2 or more, and sexual dysfunction were extracted. With logistic regression models, the relation between dose and outcome was described. Results: Thirty-eight studies met our criteria, describing 87 subgroups and involving up to 3000 patients per outcome measure. Between the (equivalent) dose of 70 and 80 Gy, various models estimated an increase in 5-year survival (ranging from 10% to 11%), 5-year bNED for low-risk patients (5-7%), late GI complications (12-16%), late GU complications (8-10%), and erectile dysfunction (19-24%). Only for the overall 5-year bNED, results were inconclusive (range, 0-18%). Conclusions: The data suggest a relationship between dose and outcome measures, including survival. However, the strength of these conclusions is limited by the sometimes small number of studies, the incompleteness of the data, and above all, the correlational nature of the data. Unambiguous proof for the dose-response relationships can, therefore, only be obtained by conducting randomized trials

  1. A 3D QSAR Study of Betulinic Acid Derivatives as Anti-Tumor Agents Using Topomer CoMFA: Model Building Studies and Experimental Verification

    Yang Wang

    2013-08-01

    Full Text Available Betulinic acid (BA is a natural product that exerts its cytotoxicity against various malignant carcinomas without side effects by triggering the mitochondrial pathway to apoptosis. Betulin (BE, the 28-hydroxyl analog of BA, is present in large amounts (up to 30% dry weight in the outer bark of birch trees, and shares the same pentacyclic triterpenoid core as BA, yet exhibits no significant cytotoxicity. Topomer CoMFA studies were performed on 37 BA and BE derivatives and their in vitro anti-cancer activity results (reported as IC50 values against HT29 human colon cancer cells in the present study. All derivatives share a common pentacyclic triterpenoid core and the molecules were split into three pieces by cutting at the C-3 and C-28 sites with a consideration toward structural diversity. The analysis gave a leave-one-out cross-validation q2 value of 0.722 and a non-cross-validation r2 value of 0.974, which suggested that the model has good predictive ability (q2 > 0.2. The contour maps illustrated that bulky and electron-donating groups would be favorable for activity at the C-28 site, and a moderately bulky and electron-withdrawing group near the C-3 site would improve this activity. BE derivatives were designed and synthesized according to the modeling result, whereby bulky electronegative groups (maleyl, phthalyl, and hexahydrophthalyl groups were directly introduced at the C-28 position of BE. The in vitro cytotoxicity values of the given analogs against HT29 cells were consistent with the predicted values, proving that the present topomer CoMFA model is successful and that it could potentially guide the synthesis of new betulinic acid derivatives with high anti-cancer activity. The IC50 values of these three new compounds were also assayed in five other tumor cell lines. 28-O-hexahydrophthalyl BE exhibited the greatest anti-cancer activities and its IC50 values were lower than those of BA in all cell lines, excluding DU145 cells.

  2. An initial study on the estimation of time-varying volumetric treatment images and 3D tumor localization from single MV cine EPID images

    Mishra, Pankaj, E-mail: pankaj.mishra@varian.com; Mak, Raymond H.; Rottmann, Joerg; Bryant, Jonathan H.; Williams, Christopher L.; Berbeco, Ross I.; Lewis, John H. [Brigham and Women' s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Li, Ruijiang [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305 (United States)

    2014-08-15

    Purpose: In this work the authors develop and investigate the feasibility of a method to estimate time-varying volumetric images from individual MV cine electronic portal image device (EPID) images. Methods: The authors adopt a two-step approach to time-varying volumetric image estimation from a single cine EPID image. In the first step, a patient-specific motion model is constructed from 4DCT. In the second step, parameters in the motion model are tuned according to the information in the EPID image. The patient-specific motion model is based on a compact representation of lung motion represented in displacement vector fields (DVFs). DVFs are calculated through deformable image registration (DIR) of a reference 4DCT phase image (typically peak-exhale) to a set of 4DCT images corresponding to different phases of a breathing cycle. The salient characteristics in the DVFs are captured in a compact representation through principal component analysis (PCA). PCA decouples the spatial and temporal components of the DVFs. Spatial information is represented in eigenvectors and the temporal information is represented by eigen-coefficients. To generate a new volumetric image, the eigen-coefficients are updated via cost function optimization based on digitally reconstructed radiographs and projection images. The updated eigen-coefficients are then multiplied with the eigenvectors to obtain updated DVFs that, in turn, give the volumetric image corresponding to the cine EPID image. Results: The algorithm was tested on (1) Eight digital eXtended CArdiac-Torso phantom datasets based on different irregular patient breathing patterns and (2) patient cine EPID images acquired during SBRT treatments. The root-mean-squared tumor localization error is (0.73 ± 0.63 mm) for the XCAT data and (0.90 ± 0.65 mm) for the patient data. Conclusions: The authors introduced a novel method of estimating volumetric time-varying images from single cine EPID images and a PCA-based lung motion model

  3. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report

    The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer.Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes.The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%.Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making. (paper)

  4. Effectiveness of evaluating tumor vascularization using 3D power Doppler ultrasound with high-definition flow technology in the prediction of the response to neoadjuvant chemotherapy for T2 breast cancer: a preliminary report

    Shia, Wei-Chung; Chen, Dar-Ren; Huang, Yu-Len; Wu, Hwa-Koon; Kuo, Shou-Jen

    2015-10-01

    The aim of this study was to evaluate the effectiveness of advanced ultrasound (US) imaging of vascular flow and morphological features in the prediction of a pathologic complete response (pCR) and a partial response (PR) to neoadjuvant chemotherapy for T2 breast cancer. Twenty-nine consecutive patients with T2 breast cancer treated with six courses of anthracycline-based neoadjuvant chemotherapy were enrolled. Three-dimensional (3D) power Doppler US with high-definition flow (HDF) technology was used to investigate the blood flow in and morphological features of the tumors. Six vascularity quantization features, three morphological features, and two vascular direction features were selected and extracted from the US images. A support vector machine was used to evaluate the changes in vascularity after neoadjuvant chemotherapy, and pCR and PR were predicted on the basis of these changes. The most accurate prediction of pCR was achieved after the first chemotherapy cycle, with an accuracy of 93.1% and a specificity of 85.5%, while that of a PR was achieved after the second cycle, with an accuracy of 79.31% and a specificity of 72.22%. Vascularity data can be useful to predict the effects of neoadjuvant chemotherapy. Determination of changes in vascularity after neoadjuvant chemotherapy using 3D power Doppler US with HDF can generate accurate predictions of the patient response, facilitating early decision-making.

  5. 3D animace

    Klusoň, Jindřich

    2010-01-01

    Computer animation has a growing importance and application in the world. With expansion of technologies increases quality of the final animation as well as number of 3D animation software. This thesis is currently mapped animation software for creating animation in film, television industry and video games which are advisable users requirements. Of them were selected according to criteria the best - Autodesk Maya 2011. This animation software is unique with tools for creating special effects...

  6. 3D ultrafast ultrasound imaging in vivo

    Very high frame rate ultrasound imaging has recently allowed for the extension of the applications of echography to new fields of study such as the functional imaging of the brain, cardiac electrophysiology, and the quantitative imaging of the intrinsic mechanical properties of tumors, to name a few, non-invasively and in real time. In this study, we present the first implementation of Ultrafast Ultrasound Imaging in 3D based on the use of either diverging or plane waves emanating from a sparse virtual array located behind the probe. It achieves high contrast and resolution while maintaining imaging rates of thousands of volumes per second. A customized portable ultrasound system was developed to sample 1024 independent channels and to drive a 32  ×  32 matrix-array probe. Its ability to track in 3D transient phenomena occurring in the millisecond range within a single ultrafast acquisition was demonstrated for 3D Shear-Wave Imaging, 3D Ultrafast Doppler Imaging, and, finally, 3D Ultrafast combined Tissue and Flow Doppler Imaging. The propagation of shear waves was tracked in a phantom and used to characterize its stiffness. 3D Ultrafast Doppler was used to obtain 3D maps of Pulsed Doppler, Color Doppler, and Power Doppler quantities in a single acquisition and revealed, at thousands of volumes per second, the complex 3D flow patterns occurring in the ventricles of the human heart during an entire cardiac cycle, as well as the 3D in vivo interaction of blood flow and wall motion during the pulse wave in the carotid at the bifurcation. This study demonstrates the potential of 3D Ultrafast Ultrasound Imaging for the 3D mapping of stiffness, tissue motion, and flow in humans in vivo and promises new clinical applications of ultrasound with reduced intra—and inter-observer variability. (fast track communication)

  7. Massive 3D Supergravity

    Andringa, Roel; de Roo, Mees; Hohm, Olaf; Sezgin, Ergin; Townsend, Paul K

    2009-01-01

    We construct the N=1 three-dimensional supergravity theory with cosmological, Einstein-Hilbert, Lorentz Chern-Simons, and general curvature squared terms. We determine the general supersymmetric configuration, and find a family of supersymmetric adS vacua with the supersymmetric Minkowski vacuum as a limiting case. Linearizing about the Minkowski vacuum, we find three classes of unitary theories; one is the supersymmetric extension of the recently discovered `massive 3D gravity'. Another is a `new topologically massive supergravity' (with no Einstein-Hilbert term) that propagates a single (2,3/2) helicity supermultiplet.

  8. Massive 3D supergravity

    Andringa, Roel; Bergshoeff, Eric A; De Roo, Mees; Hohm, Olaf [Centre for Theoretical Physics, University of Groningen, Nijenborgh 4, 9747 AG Groningen (Netherlands); Sezgin, Ergin [George and Cynthia Woods Mitchell Institute for Fundamental Physics and Astronomy, Texas A and M University, College Station, TX 77843 (United States); Townsend, Paul K, E-mail: E.A.Bergshoeff@rug.n, E-mail: O.Hohm@rug.n, E-mail: sezgin@tamu.ed, E-mail: P.K.Townsend@damtp.cam.ac.u [Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, University of Cambridge, Wilberforce Road, Cambridge, CB3 0WA (United Kingdom)

    2010-01-21

    We construct the N=1 three-dimensional supergravity theory with cosmological, Einstein-Hilbert, Lorentz Chern-Simons, and general curvature squared terms. We determine the general supersymmetric configuration, and find a family of supersymmetric adS vacua with the supersymmetric Minkowski vacuum as a limiting case. Linearizing about the Minkowski vacuum, we find three classes of unitary theories; one is the supersymmetric extension of the recently discovered 'massive 3D gravity'. Another is a 'new topologically massive supergravity' (with no Einstein-Hilbert term) that propagates a single (2,3/2) helicity supermultiplet.

  9. TOWARDS: 3D INTERNET

    Ms. Swapnali R. Ghadge

    2013-08-01

    Full Text Available In today’s ever-shifting media landscape, it can be a complex task to find effective ways to reach your desired audience. As traditional media such as television continue to lose audience share, one venue in particular stands out for its ability to attract highly motivated audiences and for its tremendous growth potential the 3D Internet. The concept of '3D Internet' has recently come into the spotlight in the R&D arena, catching the attention of many people, and leading to a lot of discussions. Basically, one can look into this matter from a few different perspectives: visualization and representation of information, and creation and transportation of information, among others. All of them still constitute research challenges, as no products or services are yet available or foreseen for the near future. Nevertheless, one can try to envisage the directions that can be taken towards achieving this goal. People who take part in virtual worlds stay online longer with a heightened level of interest. To take advantage of that interest, diverse businesses and organizations have claimed an early stake in this fast-growing market. They include technology leaders such as IBM, Microsoft, and Cisco, companies such as BMW, Toyota, Circuit City, Coca Cola, and Calvin Klein, and scores of universities, including Harvard, Stanford and Penn State.

  10. SU-E-J-123: Assessing Segmentation Accuracy of Internal Volumes and Sub-Volumes in 4D PET/CT of Lung Tumors Using a Novel 3D Printed Phantom

    Purpose: To assess the accuracy of internal target volume (ITV) segmentation of lung tumors for treatment planning of simultaneous integrated boost (SIB) radiotherapy as seen in 4D PET/CT images, using a novel 3D-printed phantom. Methods: The insert mimics high PET tracer uptake in the core and 50% uptake in the periphery, by using a porous design at the periphery. A lung phantom with the insert was placed on a programmable moving platform. Seven breathing waveforms of ideal and patient-specific respiratory motion patterns were fed to the platform, and 4D PET/CT scans were acquired of each of them. CT images were binned into 10 phases, and PET images were binned into 5 phases following the clinical protocol. Two scenarios were investigated for segmentation: a gate 30–70 window, and no gating. The radiation oncologist contoured the outer ITV of the porous insert with on CT images, while the internal void volume with 100% uptake was contoured on PET images for being indistinguishable from the outer volume in CT images. Segmented ITVs were compared to the expected volumes based on known target size and motion. Results: 3 ideal breathing patterns, 2 regular-breathing patient waveforms, and 2 irregular-breathing patient waveforms were used for this study. 18F-FDG was used as the PET tracer. The segmented ITVs from CT closely matched the expected motion for both no gating and gate 30–70 window, with disagreement of contoured ITV with respect to the expected volume not exceeding 13%. PET contours were seen to overestimate volumes in all the cases, up to more than 40%. Conclusion: 4DPET images of a novel 3D printed phantom designed to mimic different uptake values were obtained. 4DPET contours overestimated ITV volumes in all cases, while 4DCT contours matched expected ITV volume values. Investigation of the cause and effects of the discrepancies is undergoing

  11. Corneal avascularity is due to soluble VEGF receptor-1

    Ambati, Balamurali K.; Nozaki, Miho; Singh, Nirbhai; Takeda, Atsunobu; Jani, Pooja D.; Suthar, Tushar; Albuquerque, Romulo J. C.; Richter, Elizabeth; Sakurai, Eiji; Newcomb, Michael T.; Kleinman, Mark E.; Caldwell, Ruth B.; Lin, Qing; OGURA, Yuichiro; Orecchia, Angela

    2006-01-01

    Corneal avascularity—the absence of blood vessels in the cornea—is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders1-4. But the molecular underpinnings of the avascular phenotype have until now remained obscure5-10 and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and th...

  12. 3D printing for dummies

    Hausman, Kalani Kirk

    2014-01-01

    Get started printing out 3D objects quickly and inexpensively! 3D printing is no longer just a figment of your imagination. This remarkable technology is coming to the masses with the growing availability of 3D printers. 3D printers create 3-dimensional layered models and they allow users to create prototypes that use multiple materials and colors.  This friendly-but-straightforward guide examines each type of 3D printing technology available today and gives artists, entrepreneurs, engineers, and hobbyists insight into the amazing things 3D printing has to offer. You'll discover methods for

  13. Avascular necrosis of the femoral head in HIV infected patients

    Marcos Almeida Matos

    2007-02-01

    Full Text Available Avascular necrosis (AVN of the femoral head is an emerging complication in HIV infected patients. It has been suggested that the increased incidence of AVN in this population may be caused by an increased prevalence of predisposing factors for osteonecrosis, including protease inhibitors, hyperlipidemia, corticosteroid use, alcohol and intravenous drug abuse. The aim of this study was to assess the risk factors for avascular necrosis developing in the femoral head of HIV infected individuals. This study consisted of meta-analysis of the secondary data extracted from current literature. The selected articles allowed two study groups to be drawn up for comparison. Group 1 comprised 324 individuals infected by the HIV virus, who did not present femoral head AVN. Group 2 comprised 32 HIV positive patients, who presented femoral head AVN. The parameters used for analysis were as follows: age, gender, sexual preference, use of intravenous drugs, time of diagnosis, CD4+ cell count, use of antiretroviral agents and duration, serum cholesterol and serum triglycerides. The present study found a statistically significant association between hypertriglyceridemia, hypercholesterolemia, sexual preference and intravenous drug abuse. The authors concluded that femoral head osteonecrosis is associated with hyperlipidemia (hypercholesterolemia and hypertriglyceridemia and intravenous drug abuse. This study supports the hypothesis that protease inhibitors play a role in the development of osteonecrosis through a tendency to cause hyperlipidemia.

  14. 3D monitor

    Szkandera, Jan

    2009-01-01

    Tato bakalářská práce se zabývá návrhem a realizací systému, který umožní obraz scény zobrazovaný na ploše vnímat prostorově. Prostorové vnímání 2D obrazové informace je umožněno jednak stereopromítáním a jednak tím, že se obraz mění v závislosti na poloze pozorovatele. Tato práce se zabývá hlavně druhým z těchto problémů. This Bachelor's thesis goal is to design and realize system, which allows user to perceive 2D visual information as three-dimensional. 3D visual preception of 2D image i...

  15. Mobile 3D tomograph

    Mobile tomographs often have the problem that high spatial resolution is impossible owing to the position or setup of the tomograph. While the tree tomograph developed by Messrs. Isotopenforschung Dr. Sauerwein GmbH worked well in practice, it is no longer used as the spatial resolution and measuring time are insufficient for many modern applications. The paper shows that the mechanical base of the method is sufficient for 3D CT measurements with modern detectors and X-ray tubes. CT measurements with very good statistics take less than 10 min. This means that mobile systems can be used, e.g. in examinations of non-transportable cultural objects or monuments. Enhancement of the spatial resolution of mobile tomographs capable of measuring in any position is made difficult by the fact that the tomograph has moving parts and will therefore have weight shifts. With the aid of tomographies whose spatial resolution is far higher than the mechanical accuracy, a correction method is presented for direct integration of the Feldkamp algorithm

  16. X3D: Extensible 3D Graphics Standard

    Daly, Leonard; Brutzman, Don

    2007-01-01

    The article of record as published may be located at http://dx.doi.org/10.1109/MSP.2007.905889 Extensible 3D (X3D) is the open standard for Web-delivered three-dimensional (3D) graphics. It specifies a declarative geometry definition language, a run-time engine, and an application program interface (API) that provide an interactive, animated, real-time environment for 3D graphics. The X3D specification documents are freely available, the standard can be used without paying any royalties,...

  17. 3D game environments create professional 3D game worlds

    Ahearn, Luke

    2008-01-01

    The ultimate resource to help you create triple-A quality art for a variety of game worlds; 3D Game Environments offers detailed tutorials on creating 3D models, applying 2D art to 3D models, and clear concise advice on issues of efficiency and optimization for a 3D game engine. Using Photoshop and 3ds Max as his primary tools, Luke Ahearn explains how to create realistic textures from photo source and uses a variety of techniques to portray dynamic and believable game worlds.From a modern city to a steamy jungle, learn about the planning and technological considerations for 3D modelin

  18. 3D Printing an Octohedron

    Aboufadel, Edward F.

    2014-01-01

    The purpose of this short paper is to describe a project to manufacture a regular octohedron on a 3D printer. We assume that the reader is familiar with the basics of 3D printing. In the project, we use fundamental ideas to calculate the vertices and faces of an octohedron. Then, we utilize the OPENSCAD program to create a virtual 3D model and an STereoLithography (.stl) file that can be used by a 3D printer.

  19. 3D modelling and recognition

    Rodrigues, Marcos; Robinson, Alan; Alboul, Lyuba; Brink, Willie

    2006-01-01

    3D face recognition is an open field. In this paper we present a method for 3D facial recognition based on Principal Components Analysis. The method uses a relatively large number of facial measurements and ratios and yields reliable recognition. We also highlight our approach to sensor development for fast 3D model acquisition and automatic facial feature extraction.

  20. 3-D contextual Bayesian classifiers

    Larsen, Rasmus

    distribution for the pixel values as well as a prior distribution for the configuration of class variables within the cross that is made of a pixel and its four nearest neighbours. We will extend these algorithms to 3-D, i.e. we will specify a simultaneous Gaussian distribution for a pixel and its 6 nearest 3......-D neighbours, and generalise the class variable configuration distributions within the 3-D cross given in 2-D algorithms. The new 3-D algorithms are tested on a synthetic 3-D multivariate dataset....

  1. Taming Supersymmetric Defects in 3d-3d Correspondence

    Gang, Dongmin; Romo, Mauricio; Yamazaki, Masahito

    2015-01-01

    We study knots in 3d Chern-Simons theory with complex gauge group $SL(N,\\mathbb{C})$, in the context of its relation with 3d $\\mathcal{N}=2$ theory (the so-called 3d-3d correspondence). The defect has either co-dimension 2 or co-dimension 4 inside the 6d $(2,0)$ theory, which is compactified on a 3-manifold $\\hat{M}$. We identify such defects in various corners of the 3d-3d correspondence, namely in 3d $SL(N,\\mathbb{C})$ Chern-Simons theory, in 3d $\\mathcal{N}=2$ theory, in 5d $\\mathcal{N}=2$ super Yang-Mills theory, and in the M-theory holographic dual. We can make quantitative checks of the 3d-3d correspondence by computing partition functions at each of these theories. This Letter is a companion to a longer paper, which contains more details and more results.

  2. 3D Printing Functional Nanocomposites

    Leong, Yew Juan

    2016-01-01

    3D printing presents the ability of rapid prototyping and rapid manufacturing. Techniques such as stereolithography (SLA) and fused deposition molding (FDM) have been developed and utilized since the inception of 3D printing. In such techniques, polymers represent the most commonly used material for 3D printing due to material properties such as thermo plasticity as well as its ability to be polymerized from monomers. Polymer nanocomposites are polymers with nanomaterials composited into the ...

  3. 3D IBFV : Hardware-Accelerated 3D Flow Visualization

    Telea, Alexandru; Wijk, Jarke J. van

    2003-01-01

    We present a hardware-accelerated method for visualizing 3D flow fields. The method is based on insertion, advection, and decay of dye. To this aim, we extend the texture-based IBFV technique for 2D flow visualization in two main directions. First, we decompose the 3D flow visualization problem in a

  4. 3D Elevation Program—Virtual USA in 3D

    Lukas, Vicki; Stoker, J.M.

    2016-01-01

    The U.S. Geological Survey (USGS) 3D Elevation Program (3DEP) uses a laser system called ‘lidar’ (light detection and ranging) to create a virtual reality map of the Nation that is very accurate. 3D maps have many uses with new uses being discovered all the time.  

  5. 3D for Graphic Designers

    Connell, Ellery

    2011-01-01

    Helping graphic designers expand their 2D skills into the 3D space The trend in graphic design is towards 3D, with the demand for motion graphics, animation, photorealism, and interactivity rapidly increasing. And with the meteoric rise of iPads, smartphones, and other interactive devices, the design landscape is changing faster than ever.2D digital artists who need a quick and efficient way to join this brave new world will want 3D for Graphic Designers. Readers get hands-on basic training in working in the 3D space, including product design, industrial design and visualization, modeling, ani

  6. 3-D printers for libraries

    Griffey, Jason

    2014-01-01

    As the maker movement continues to grow and 3-D printers become more affordable, an expanding group of hobbyists is keen to explore this new technology. In the time-honored tradition of introducing new technologies, many libraries are considering purchasing a 3-D printer. Jason Griffey, an early enthusiast of 3-D printing, has researched the marketplace and seen several systems first hand at the Consumer Electronics Show. In this report he introduces readers to the 3-D printing marketplace, covering such topics asHow fused deposition modeling (FDM) printing workBasic terminology such as build

  7. A 3-D Contextual Classifier

    Larsen, Rasmus

    1997-01-01

    . This includes the specification of a Gaussian distribution for the pixel values as well as a prior distribution for the configuration of class variables within the cross that is m ade of a pixel and its four nearest neighbours. We will extend this algorithm to 3-D, i.e. we will specify a simultaneous Gaussian...... distr ibution for a pixel and its 6 nearest 3-D neighbours, and generalise the class variable configuration distribution within the 3-D cross. The algorithm is tested on a synthetic 3-D multivariate dataset....

  8. 3D Bayesian contextual classifiers

    Larsen, Rasmus

    2000-01-01

    We extend a series of multivariate Bayesian 2-D contextual classifiers to 3-D by specifying a simultaneous Gaussian distribution for the feature vectors as well as a prior distribution of the class variables of a pixel and its 6 nearest 3-D neighbours.......We extend a series of multivariate Bayesian 2-D contextual classifiers to 3-D by specifying a simultaneous Gaussian distribution for the feature vectors as well as a prior distribution of the class variables of a pixel and its 6 nearest 3-D neighbours....

  9. Interactive 3D multimedia content

    Cellary, Wojciech

    2012-01-01

    The book describes recent research results in the areas of modelling, creation, management and presentation of interactive 3D multimedia content. The book describes the current state of the art in the field and identifies the most important research and design issues. Consecutive chapters address these issues. These are: database modelling of 3D content, security in 3D environments, describing interactivity of content, searching content, visualization of search results, modelling mixed reality content, and efficient creation of interactive 3D content. Each chapter is illustrated with example a

  10. Improvement of 3D Scanner

    2003-01-01

    The disadvantage remaining in 3D scanning system and its reasons are discussed. A new host-and-slave structure with high speed image acquisition and processing system is proposed to quicken the image processing and improve the performance of 3D scanning system.

  11. 3D Printing for Bricks

    ECT Team, Purdue

    2015-01-01

    Building Bytes, by Brian Peters, is a project that uses desktop 3D printers to print bricks for architecture. Instead of using an expensive custom-made printer, it uses a normal standard 3D printer which is available for everyone and makes it more accessible and also easier for fabrication.

  12. Modular 3-D Transport model

    MT3D was first developed by Chunmiao Zheng in 1990 at S.S. Papadopulos & Associates, Inc. with partial support from the U.S. Environmental Protection Agency (USEPA). Starting in 1990, MT3D was released as a pubic domain code from the USEPA. Commercial versions with enhanced capab...

  13. Using 3D in Visualization

    Wood, Jo; Kirschenbauer, Sabine; Döllner, Jürgen;

    2005-01-01

    The notion of three-dimensionality is applied to five stages of the visualization pipeline. While 3D visulization is most often associated with the visual mapping and representation of data, this chapter also identifies its role in the management and assembly of data, and in the media used...... to display 3D imagery. The extra cartographic degree of freedom offered by using 3D is explored and offered as a motivation for employing 3D in visualization. The use of VR and the construction of virtual environments exploit navigational and behavioral realism, but become most usefil when combined...... with abstracted representations embedded in a 3D space. The interactions between development of geovisualization, the technology used to implement it and the theory surrounding cartographic representation are explored. The dominance of computing technologies, driven particularly by the gaming industry...

  14. PLOT3D/AMES, APOLLO UNIX VERSION USING GMR3D (WITHOUT TURB3D)

    Buning, P.

    1994-01-01

    PLOT3D is an interactive graphics program designed to help scientists visualize computational fluid dynamics (CFD) grids and solutions. Today, supercomputers and CFD algorithms can provide scientists with simulations of such highly complex phenomena that obtaining an understanding of the simulations has become a major problem. Tools which help the scientist visualize the simulations can be of tremendous aid. PLOT3D/AMES offers more functions and features, and has been adapted for more types of computers than any other CFD graphics program. Version 3.6b+ is supported for five computers and graphic libraries. Using PLOT3D, CFD physicists can view their computational models from any angle, observing the physics of problems and the quality of solutions. As an aid in designing aircraft, for example, PLOT3D's interactive computer graphics can show vortices, temperature, reverse flow, pressure, and dozens of other characteristics of air flow during flight. As critical areas become obvious, they can easily be studied more closely using a finer grid. PLOT3D is part of a computational fluid dynamics software cycle. First, a program such as 3DGRAPE (ARC-12620) helps the scientist generate computational grids to model an object and its surrounding space. Once the grids have been designed and parameters such as the angle of attack, Mach number, and Reynolds number have been specified, a "flow-solver" program such as INS3D (ARC-11794 or COS-10019) solves the system of equations governing fluid flow, usually on a supercomputer. Grids sometimes have as many as two million points, and the "flow-solver" produces a solution file which contains density, x- y- and z-momentum, and stagnation energy for each grid point. With such a solution file and a grid file containing up to 50 grids as input, PLOT3D can calculate and graphically display any one of 74 functions, including shock waves, surface pressure, velocity vectors, and particle traces. PLOT3D's 74 functions are organized into

  15. PLOT3D/AMES, APOLLO UNIX VERSION USING GMR3D (WITH TURB3D)

    Buning, P.

    1994-01-01

    PLOT3D is an interactive graphics program designed to help scientists visualize computational fluid dynamics (CFD) grids and solutions. Today, supercomputers and CFD algorithms can provide scientists with simulations of such highly complex phenomena that obtaining an understanding of the simulations has become a major problem. Tools which help the scientist visualize the simulations can be of tremendous aid. PLOT3D/AMES offers more functions and features, and has been adapted for more types of computers than any other CFD graphics program. Version 3.6b+ is supported for five computers and graphic libraries. Using PLOT3D, CFD physicists can view their computational models from any angle, observing the physics of problems and the quality of solutions. As an aid in designing aircraft, for example, PLOT3D's interactive computer graphics can show vortices, temperature, reverse flow, pressure, and dozens of other characteristics of air flow during flight. As critical areas become obvious, they can easily be studied more closely using a finer grid. PLOT3D is part of a computational fluid dynamics software cycle. First, a program such as 3DGRAPE (ARC-12620) helps the scientist generate computational grids to model an object and its surrounding space. Once the grids have been designed and parameters such as the angle of attack, Mach number, and Reynolds number have been specified, a "flow-solver" program such as INS3D (ARC-11794 or COS-10019) solves the system of equations governing fluid flow, usually on a supercomputer. Grids sometimes have as many as two million points, and the "flow-solver" produces a solution file which contains density, x- y- and z-momentum, and stagnation energy for each grid point. With such a solution file and a grid file containing up to 50 grids as input, PLOT3D can calculate and graphically display any one of 74 functions, including shock waves, surface pressure, velocity vectors, and particle traces. PLOT3D's 74 functions are organized into

  16. Avascular necrosis of the femoral head at 2 years after pertrochanteric fracture surgery: Case report

    Bogdan Deleanu

    2016-02-01

    Conclusion: The avascular necrosis of the femoral head is a complication of pertrochanteric fractures that can not be foreseen or avoided. The optimal treatment in these cases is uncemented total hip arthroplasty.

  17. Unassisted 3D camera calibration

    Atanassov, Kalin; Ramachandra, Vikas; Nash, James; Goma, Sergio R.

    2012-03-01

    With the rapid growth of 3D technology, 3D image capture has become a critical part of the 3D feature set on mobile phones. 3D image quality is affected by the scene geometry as well as on-the-device processing. An automatic 3D system usually assumes known camera poses accomplished by factory calibration using a special chart. In real life settings, pose parameters estimated by factory calibration can be negatively impacted by movements of the lens barrel due to shaking, focusing, or camera drop. If any of these factors displaces the optical axes of either or both cameras, vertical disparity might exceed the maximum tolerable margin and the 3D user may experience eye strain or headaches. To make 3D capture more practical, one needs to consider unassisted (on arbitrary scenes) calibration. In this paper, we propose an algorithm that relies on detection and matching of keypoints between left and right images. Frames containing erroneous matches, along with frames with insufficiently rich keypoint constellations, are detected and discarded. Roll, pitch yaw , and scale differences between left and right frames are then estimated. The algorithm performance is evaluated in terms of the remaining vertical disparity as compared to the maximum tolerable vertical disparity.

  18. Color 3D Reverse Engineering

    2002-01-01

    This paper presents a principle and a method of col or 3D laser scanning measurement. Based on the fundamental monochrome 3D measureme nt study, color information capture, color texture mapping, coordinate computati on and other techniques are performed to achieve color 3D measurement. The syste m is designed and composed of a line laser light emitter, one color CCD camera, a motor-driven rotary filter, a circuit card and a computer. Two steps in captu ring object's images in the measurement process: Firs...

  19. 3-D neutron transport benchmarks

    A set of 3-D neutron transport benchmark problems proposed by the Osaka University to NEACRP in 1988 has been calculated by many participants and the corresponding results are summarized in this report. The results of Keff, control rod worth and region-averaged fluxes for the four proposed core models, calculated by using various 3-D transport codes are compared and discussed. The calculational methods used were: Monte Carlo, Discrete Ordinates (Sn), Spherical Harmonics (Pn), Nodal Transport and others. The solutions of the four core models are quite useful as benchmarks for checking the validity of 3-D neutron transport codes

  20. 3D on the internet

    Puntar, Matej

    2012-01-01

    The purpose of this thesis is the presentation of already established and new technologies of displaying 3D content in a web browser. The thesis begins with a short presentation of the history of 3D content available on the internet and its development together with advantages and disadvantages of individual technologies. The latter two are described in detail as well is their use and the differences among them. Special emphasis has been given to WebGL, the newest technology of 3D conte...

  1. 5-axis 3D Printer

    Grutle, Øyvind Kallevik

    2015-01-01

    3D printers have in recent years become extremely popular. Even though 3D printing technology have existed since the late 1980's, it is now considered one of the most significant technological breakthroughs of the twenty-first century. Several different 3D printing processes have been invented during the years. But it is the fused deposition modeling (FDM) which was one of the first invented that is considered the most popular today. Even though the FDM process is the most popular, it still s...

  2. Handbook of 3D integration

    Garrou , Philip; Ramm , Peter

    2014-01-01

    Edited by key figures in 3D integration and written by top authors from high-tech companies and renowned research institutions, this book covers the intricate details of 3D process technology.As such, the main focus is on silicon via formation, bonding and debonding, thinning, via reveal and backside processing, both from a technological and a materials science perspective. The last part of the book is concerned with assessing and enhancing the reliability of the 3D integrated devices, which is a prerequisite for the large-scale implementation of this emerging technology. Invaluable reading fo

  3. Exploration of 3D Printing

    Lin, Zeyu

    2014-01-01

    3D printing technology is introduced and defined in this Thesis. Some methods of 3D printing are illustrated and their principles are explained with pictures. Most of the essential parts are presented with pictures and their effects are explained within the whole system. Problems on Up! Plus 3D printer are solved and a DIY product is made with this machine. The processes of making product are recorded and the items which need to be noticed during the process are the highlight in this th...

  4. Tuotekehitysprojekti: 3D-tulostin

    Pihlajamäki, Janne

    2011-01-01

    Opinnäytetyössä tutustuttiin 3D-tulostamisen teknologiaan. Työssä käytiin läpi 3D-tulostimesta tehty tuotekehitysprojekti. Sen lisäksi esiteltiin yleisellä tasolla tuotekehitysprosessi ja syntyneiden tulosten mahdollisia suojausmenetelmiä. Tavoitteena tässä työssä oli kehittää markkinoilta jo löytyvää kotitulostin-tasoista 3D-laiteteknologiaa lähemmäksi ammattilaistason ratkaisua. Tavoitteeseen pyrittiin keskittymällä parantamaan laitteella saavutettavaa tulostustarkkuutta ja -nopeutt...

  5. Magnetic resonance imaging of avascular necrosis of the femoral head

    To evaluate the diagnostic value and limitation of magnetic resonance imaging (MRI) in avascular necrosis of the femoral head (ANF), clinical stages and types were examined on MRI scans of 68 femoral heads of 46 ANF patients. Stage 1 patients fell into two groups: (1) stage 1-A group of real ANF in which abnormal findings were observed on both MRI and bone scanning and (2) stage 1-B group of asymptomatic ANF in which MRI detected abnormality that was missed by bone scanning. In these groups, MRI showed inhomogeneous, band, and spotty patterns. Stage 2 or 3 patients tended to have homogeneous or ring-pattern hypointensities on MRI. Histological examination showed that repair reaction at the marginal site of hypointensity was partly responsible for the occurrence of hypointensities. In Stage 4 patients, not only femoral head but also acetabular site was visible as homogeneous hypointensity, which was similar to that in osteoarthritis. Because repair areas, as well as necrotic areas, were frequently visualized as hypointensities in Stages 2 or more, MRI might overestimate necrotic areas. (N.K.)

  6. Main: TATCCAYMOTIFOSRAMY3D [PLACE

    Full Text Available TATCCAYMOTIFOSRAMY3D S000256 01-August-2006 (last modified) kehi TATCCAY motif found in rice (O. ... otif and G motif (see S000130) are responsible for sugar ... repression (Toyofuku et al. 1998); GATA; amylase; ...

  7. Heterodyne 3D ghost imaging

    Yang, Xu; Zhang, Yong; Yang, Chenghua; Xu, Lu; Wang, Qiang; Zhao, Yuan

    2016-06-01

    Conventional three dimensional (3D) ghost imaging measures range of target based on pulse fight time measurement method. Due to the limit of data acquisition system sampling rate, range resolution of the conventional 3D ghost imaging is usually low. In order to take off the effect of sampling rate to range resolution of 3D ghost imaging, a heterodyne 3D ghost imaging (HGI) system is presented in this study. The source of HGI is a continuous wave laser instead of pulse laser. Temporal correlation and spatial correlation of light are both utilized to obtain the range image of target. Through theory analysis and numerical simulations, it is demonstrated that HGI can obtain high range resolution image with low sampling rate.

  8. Conducting polymer 3D microelectrodes

    Sasso, Luigi; Vazquez, Patricia; Vedarethinam, Indumathi;

    2010-01-01

    Conducting polymer 3D microelectrodes have been fabricated for possible future neurological applications. A combination of micro-fabrication techniques and chemical polymerization methods has been used to create pillar electrodes in polyaniline and polypyrrole. The thin polymer films obtained...

  9. Combinatorial 3D Mechanical Metamaterials

    Coulais, Corentin; Teomy, Eial; de Reus, Koen; Shokef, Yair; van Hecke, Martin

    2015-03-01

    We present a class of elastic structures which exhibit 3D-folding motion. Our structures consist of cubic lattices of anisotropic unit cells that can be tiled in a complex combinatorial fashion. We design and 3d-print this complex ordered mechanism, in which we combine elastic hinges and defects to tailor the mechanics of the material. Finally, we use this large design space to encode smart functionalities such as surface patterning and multistability.

  10. AI 3D Cybug Gaming

    Ahmed, Zeeshan

    2010-01-01

    In this short paper I briefly discuss 3D war Game based on artificial intelligence concepts called AI WAR. Going in to the details, I present the importance of CAICL language and how this language is used in AI WAR. Moreover I also present a designed and implemented 3D War Cybug for AI WAR using CAICL and discus the implemented strategy to defeat its enemies during the game life.

  11. 3D Face Appearance Model

    Lading, Brian; Larsen, Rasmus; Åström, Kalle

    2006-01-01

    We build a 3d face shape model, including inter- and intra-shape variations, derive the analytical jacobian of its resulting 2d rendered image, and show example of its fitting performance with light, pose, id, expression and texture variations.}......We build a 3d face shape model, including inter- and intra-shape variations, derive the analytical jacobian of its resulting 2d rendered image, and show example of its fitting performance with light, pose, id, expression and texture variations.}...

  12. 3D Face Apperance Model

    Lading, Brian; Larsen, Rasmus; Astrom, K

    2006-01-01

    We build a 3D face shape model, including inter- and intra-shape variations, derive the analytical Jacobian of its resulting 2D rendered image, and show example of its fitting performance with light, pose, id, expression and texture variations......We build a 3D face shape model, including inter- and intra-shape variations, derive the analytical Jacobian of its resulting 2D rendered image, and show example of its fitting performance with light, pose, id, expression and texture variations...

  13. The Effect of Flattening Filter Free on Three-dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), and Volumetric Modulated Arc Therapy (VMAT) Plans for Metastatic Brain Tumors from Non-small Cell Lung Cancer.

    Shi, Li-Wan; Lai, You-Qun; Lin, Qin; Ha, Hui-Ming; Fu, Li-Rong

    2015-07-01

    Flattening filter free (FFF) may affect outcome measures of radiotherapy. The objective of this study is to compare the dosimetric parameters in three types of radiotherapy plans, three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT), with or without the flattening filter (FF), developed for the treatment of metastatic brain tumors from non-small cell lung cancer (NSCLC). From July 2013 to October 2013, 3D-CRT, IMRT, and VMAT treatment plans were designed using 6 MV and 10 MV, with and without FF, for 10 patients with brain metastasis from NSCLC. The evaluation of the treatment plans included homogeneity index (HI), conformity index (CI), monitor units (MU), mean dose (Dmean), treatment time, and the influence of FFF on volumes. There was no difference in CI or HI between FFF and FF models with 3D-CRT, IMRT, and VMAT plans. At 6 MV, a lower Dmean was seen in the FFF model of 3D-CRT and in the VMAT plan at 10 MV. In the IMRT 6 MV, IMRT 10 MV, and VMAT 10 MV plans, higher MUs were seen in the FFF models. FFF treatments are similar in quality to FF plans, generally lead to more monitor units, and are associated with shorter treatment times. FFF plans ranked by the order of superiority in terms of a time advantage are VMAT, 3D-CRT, and IMRT. PMID:26011493

  14. Biomechanical comparisons between a new avascular necrosis of femaral head stem based on Chinese patients with avascular necrosis and two other designs

    ZHANG Qiang; CHENG Cheng-kung; WEI Hung-wen; DONG Xiang; CHEN Yi-ting; LAI Yu-shu; WANG Yan

    2013-01-01

    Background There is a relatively high failure rate of the femoral component in patients with avascuiar necrosis at the intermediate-term follow-up.Improving the geometrical fit of the femoral stem against the medullary canal may help to provide long-term survivorship of the hip replacement for patients with avascular necrosis.Methods We designed a specific stem,based on morphometric studies of proximal femoral canals in Chinese avascular necrosis patients and evaluated the stem by finite element analyses,comparing the novel stem with two commercially available and commonly used stems.Results The morphometric data from avascular necrosis patients showed specific geometric differences in the proximal femoral canal,including profile curves in both the sagittal and coronary planes than the patients with femoral neck fracture.The shorter stemmed prostheses (Fitmore(R) and our stem) performed better than the longer stemmed prosthesis (VerSys(R)).Conclusions This is the first study to investigate the femoral geometries of Chinese avascular necrosis patients.Our stem provides better stability and is theoretically beneficial to bone ingrowth,which may increase the long-term stability and fixation of the implant.

  15. From 3D view to 3D print

    Dima, M.; Farisato, G.; Bergomi, M.; Viotto, V.; Magrin, D.; Greggio, D.; Farinato, J.; Marafatto, L.; Ragazzoni, R.; Piazza, D.

    2014-08-01

    In the last few years 3D printing is getting more and more popular and used in many fields going from manufacturing to industrial design, architecture, medical support and aerospace. 3D printing is an evolution of bi-dimensional printing, which allows to obtain a solid object from a 3D model, realized with a 3D modelling software. The final product is obtained using an additive process, in which successive layers of material are laid down one over the other. A 3D printer allows to realize, in a simple way, very complex shapes, which would be quite difficult to be produced with dedicated conventional facilities. Thanks to the fact that the 3D printing is obtained superposing one layer to the others, it doesn't need any particular work flow and it is sufficient to simply draw the model and send it to print. Many different kinds of 3D printers exist based on the technology and material used for layer deposition. A common material used by the toner is ABS plastics, which is a light and rigid thermoplastic polymer, whose peculiar mechanical properties make it diffusely used in several fields, like pipes production and cars interiors manufacturing. I used this technology to create a 1:1 scale model of the telescope which is the hardware core of the space small mission CHEOPS (CHaracterising ExOPlanets Satellite) by ESA, which aims to characterize EXOplanets via transits observations. The telescope has a Ritchey-Chrétien configuration with a 30cm aperture and the launch is foreseen in 2017. In this paper, I present the different phases for the realization of such a model, focusing onto pros and cons of this kind of technology. For example, because of the finite printable volume (10×10×12 inches in the x, y and z directions respectively), it has been necessary to split the largest parts of the instrument in smaller components to be then reassembled and post-processed. A further issue is the resolution of the printed material, which is expressed in terms of layers

  16. YouDash3D: exploring stereoscopic 3D gaming for 3D movie theaters

    Schild, Jonas; Seele, Sven; Masuch, Maic

    2012-03-01

    Along with the success of the digitally revived stereoscopic cinema, events beyond 3D movies become attractive for movie theater operators, i.e. interactive 3D games. In this paper, we present a case that explores possible challenges and solutions for interactive 3D games to be played by a movie theater audience. We analyze the setting and showcase current issues related to lighting and interaction. Our second focus is to provide gameplay mechanics that make special use of stereoscopy, especially depth-based game design. Based on these results, we present YouDash3D, a game prototype that explores public stereoscopic gameplay in a reduced kiosk setup. It features live 3D HD video stream of a professional stereo camera rig rendered in a real-time game scene. We use the effect to place the stereoscopic effigies of players into the digital game. The game showcases how stereoscopic vision can provide for a novel depth-based game mechanic. Projected trigger zones and distributed clusters of the audience video allow for easy adaptation to larger audiences and 3D movie theater gaming.

  17. Remote 3D Medical Consultation

    Welch, Greg; Sonnenwald, Diane H.; Fuchs, Henry; Cairns, Bruce; Mayer-Patel, Ketan; Yang, Ruigang; State, Andrei; Towles, Herman; Ilie, Adrian; Krishnan, Srinivas; Söderholm, Hanna M.

    Two-dimensional (2D) video-based telemedical consultation has been explored widely in the past 15-20 years. Two issues that seem to arise in most relevant case studies are the difficulty associated with obtaining the desired 2D camera views, and poor depth perception. To address these problems we are exploring the use of a small array of cameras to synthesize a spatially continuous range of dynamic three-dimensional (3D) views of a remote environment and events. The 3D views can be sent across wired or wireless networks to remote viewers with fixed displays or mobile devices such as a personal digital assistant (PDA). The viewpoints could be specified manually or automatically via user head or PDA tracking, giving the remote viewer virtual head- or hand-slaved (PDA-based) remote cameras for mono or stereo viewing. We call this idea remote 3D medical consultation (3DMC). In this article we motivate and explain the vision for 3D medical consultation; we describe the relevant computer vision/graphics, display, and networking research; we present a proof-of-concept prototype system; and we present some early experimental results supporting the general hypothesis that 3D remote medical consultation could offer benefits over conventional 2D televideo.

  18. Novel 3D media technologies

    Dagiuklas, Tasos

    2015-01-01

    This book describes recent innovations in 3D media and technologies, with coverage of 3D media capturing, processing, encoding, and adaptation, networking aspects for 3D Media, and quality of user experience (QoE). The contributions are based on the results of the FP7 European Project ROMEO, which focuses on new methods for the compression and delivery of 3D multi-view video and spatial audio, as well as the optimization of networking and compression jointly across the future Internet. The delivery of 3D media to individual users remains a highly challenging problem due to the large amount of data involved, diverse network characteristics and user terminal requirements, as well as the user’s context such as their preferences and location. As the number of visual views increases, current systems will struggle to meet the demanding requirements in terms of delivery of consistent video quality to fixed and mobile users. ROMEO will present hybrid networking solutions that combine the DVB-T2 and DVB-NGH broadcas...

  19. 3D future internet media

    Dagiuklas, Tasos

    2014-01-01

    This book describes recent innovations in 3D media and technologies, with coverage of 3D media capturing, processing, encoding, and adaptation, networking aspects for 3D Media, and quality of user experience (QoE). The main contributions are based on the results of the FP7 European Projects ROMEO, which focus on new methods for the compression and delivery of 3D multi-view video and spatial audio, as well as the optimization of networking and compression jointly across the Future Internet (www.ict-romeo.eu). The delivery of 3D media to individual users remains a highly challenging problem due to the large amount of data involved, diverse network characteristics and user terminal requirements, as well as the user’s context such as their preferences and location. As the number of visual views increases, current systems will struggle to meet the demanding requirements in terms of delivery of constant video quality to both fixed and mobile users. ROMEO will design and develop hybrid-networking solutions that co...

  20. Materialedreven 3d digital formgivning

    Hansen, Flemming Tvede

    2010-01-01

    Formålet med forskningsprojektet er for det første at understøtte keramikeren i at arbejde eksperimenterende med digital formgivning, og for det andet at bidrage til en tværfaglig diskurs om brugen af digital formgivning. Forskningsprojektet fokuserer på 3d formgivning og derved på 3d digital...... formgivning og Rapid Prototyping (RP). RP er en fællesbetegnelse for en række af de teknikker, der muliggør at overføre den digitale form til 3d fysisk form. Forskningsprojektet koncentrerer sig om to overordnede forskningsspørgsmål. Det første handler om, hvordan viden og erfaring indenfor det keramiske...... fagområde kan blive udnyttet i forhold til 3d digital formgivning. Det andet handler om, hvad en sådan tilgang kan bidrage med, og hvordan den kan blive udnyttet i et dynamisk samspil med det keramiske materiale i formgivningen af 3d keramiske artefakter. Materialedreven formgivning er karakteriseret af en...

  1. Modification of 3D milling machine to 3D printer

    Halamíček, Lukáš

    2015-01-01

    Tato práce se zabývá přestavbou gravírovací frézky na 3D tiskárnu. V první části se práce zabývá možnými technologiemi 3D tisku a možností jejich využití u přestavby. Dále jsou popsány a vybrány vhodné součásti pro přestavbu. V další části je realizováno řízení ohřevu podložky, trysky a řízení posuvu drátu pomocí softwaru TwinCat od společnosti Beckhoff na průmyslovém počítači. Výsledkem práce by měla být oživená 3D tiskárna. This thesis deals with rebuilding of engraving machine to 3D pri...

  2. 3D Imager and Method for 3D imaging

    Kumar, P.; Staszewski, R.; Charbon, E.

    2013-01-01

    3D imager comprising at least one pixel, each pixel comprising a photodetectorfor detecting photon incidence and a time-to-digital converter system configured for referencing said photon incidence to a reference clock, and further comprising a reference clock generator provided for generating the re

  3. Crowded Field 3D Spectroscopy

    Becker, T; Roth, M M; Becker, Thomas; Fabrika, Sergei; Roth, Martin M.

    2003-01-01

    The quantitative spectroscopy of stellar objects in complex environments is mainly limited by the ability of separating the object from the background. Standard slit spectroscopy, restricting the field of view to one dimension, is obviously not the proper technique in general. The emerging Integral Field (3D) technique with spatially resolved spectra of a two-dimensional field of view provides a great potential for applying advanced subtraction methods. In this paper an image reconstruction algorithm to separate point sources and a smooth background is applied to 3D data. Several performance tests demonstrate the photometric quality of the method. The algorithm is applied to real 3D observations of a sample Planetary Nebula in M31, whose spectrum is contaminated by the bright and complex galaxy background. The ability of separating sources is also studied in a crowded stellar field in M33.

  4. Validation of TRAB-3D

    TRAB-3D is a reactor dynamics code with three-dimensional neutronics coupled to core and circuit thermal-hydraulics. The code, entirely developed at VTT, can be used in transient and accident analyses of boiling (BWR) and pressurized water (PWR) reactors with rectangular fuel bundle geometry. The validation history of TRAB-3D includes calculation of international benchmark exercises, as well as comparisons with measured data from real plant transients. The most recent validation case is a load rejection test performed at the Olkiluoto 1 nuclear power plant in 1998 in connection with the power uprating project. The fact that there is local power measurement data available from this test makes it a suitable case for three-dimensional core model validation. The agreement between the results of the TRAB-3D calculation and the measurements is very good. (orig.)

  5. 3D-grafiikkamoottori mobiililaitteille

    Vahlman, Lauri

    2014-01-01

    Tässä insinöörityössä käydään läpi mobiililaitteille suunnatun yksinkertaisen 3D-grafiikkamoottorin suunnittelu ja toteutus käyttäen OpenGL ES -rajapintaa. Työssä esitellään grafiikkamoottorin toteutuksessa käytettyjä tekniikoita sekä tutustutaan moottorin rakenteeseen ja toteutuksellisiin yksityiskohtiin. Työn alkupuolella tutustutaan myös modernin 3D-grafiikan yleisiin periaatteisiin ja toimintaan sekä käydään läpi 3D-grafiikkaan liittyviä suorituskykyongelmia. Työn loppupuolella esitel...

  6. Markerless 3D Face Tracking

    Walder, Christian; Breidt, Martin; Bulthoff, Heinrich;

    2009-01-01

    We present a novel algorithm for the markerless tracking of deforming surfaces such as faces. We acquire a sequence of 3D scans along with color images at 40Hz. The data is then represented by implicit surface and color functions, using a novel partition-of-unity type method of efficiently...... combining local regressors using nearest neighbor searches. Both these functions act on the 4D space of 3D plus time, and use temporal information to handle the noise in individual scans. After interactive registration of a template mesh to the first frame, it is then automatically deformed to track...... the scanned surface, using the variation of both shape and color as features in a dynamic energy minimization problem. Our prototype system yields high-quality animated 3D models in correspondence, at a rate of approximately twenty seconds per timestep. Tracking results for faces and other objects...

  7. 3D vector flow imaging

    Pihl, Michael Johannes

    The main purpose of this PhD project is to develop an ultrasonic method for 3D vector flow imaging. The motivation is to advance the field of velocity estimation in ultrasound, which plays an important role in the clinic. The velocity of blood has components in all three spatial dimensions, yet...... conventional methods can estimate only the axial component. Several approaches for 3D vector velocity estimation have been suggested, but none of these methods have so far produced convincing in vivo results nor have they been adopted by commercial manufacturers. The basis for this project is the Transverse...... on the TO fields are suggested. They can be used to optimize the TO method. In the third part, a TO method for 3D vector velocity estimation is proposed. It employs a 2D phased array transducer and decouples the velocity estimation into three velocity components, which are estimated simultaneously based on 5...

  8. 3D proton beam micromachining

    Focused high energy ion beam micromachining is the newest of the micromachining techniques. There are about 50 scanning proton microprobe facilities worldwide, but so far only few of them showed activity in this promising field. High energy ion beam micromachining using a direct-write scanning MeV ion beam is capable of producing 3D microstructures and components with well defined lateral and depth geometry. The technique has high potential in the manufacture of 3D molds, stamps, and masks for X-ray lithography (LIGA), and also in the rapid prototyping of microcomponents either for research purposes or for components testing prior to batch production. (R.P.)

  9. 3D Computations and Experiments

    Couch, R; Faux, D; Goto, D; Nikkel, D

    2004-04-05

    This project consists of two activities. Task A, Simulations and Measurements, combines all the material model development and associated numerical work with the materials-oriented experimental activities. The goal of this effort is to provide an improved understanding of dynamic material properties and to provide accurate numerical representations of those properties for use in analysis codes. Task B, ALE3D Development, involves general development activities in the ALE3D code with the focus of improving simulation capabilities for problems of mutual interest to DoD and DOE. Emphasis is on problems involving multi-phase flow, blast loading of structures and system safety/vulnerability studies.

  10. Multizone paper platform for 3D cell cultures.

    Ratmir Derda

    Full Text Available In vitro 3D culture is an important model for tissues in vivo. Cells in different locations of 3D tissues are physiologically different, because they are exposed to different concentrations of oxygen, nutrients, and signaling molecules, and to other environmental factors (temperature, mechanical stress, etc. The majority of high-throughput assays based on 3D cultures, however, can only detect the average behavior of cells in the whole 3D construct. Isolation of cells from specific regions of 3D cultures is possible, but relies on low-throughput techniques such as tissue sectioning and micromanipulation. Based on a procedure reported previously ("cells-in-gels-in-paper" or CiGiP, this paper describes a simple method for culture of arrays of thin planar sections of tissues, either alone or stacked to create more complex 3D tissue structures. This procedure starts with sheets of paper patterned with hydrophobic regions that form 96 hydrophilic zones. Serial spotting of cells suspended in extracellular matrix (ECM gel onto the patterned paper creates an array of 200 micron-thick slabs of ECM gel (supported mechanically by cellulose fibers containing cells. Stacking the sheets with zones aligned on top of one another assembles 96 3D multilayer constructs. De-stacking the layers of the 3D culture, by peeling apart the sheets of paper, "sections" all 96 cultures at once. It is, thus, simple to isolate 200-micron-thick cell-containing slabs from each 3D culture in the 96-zone array. Because the 3D cultures are assembled from multiple layers, the number of cells plated initially in each layer determines the spatial distribution of cells in the stacked 3D cultures. This capability made it possible to compare the growth of 3D tumor models of different spatial composition, and to examine the migration of cells in these structures.