Development of the premature infant nose throat-model (PrINT-Model): an upper airway replica of a premature neonate for the study of aerosol delivery

Clinical efficacy of aerosol therapy in premature newborns depends on the efficiency of delivery of aerosolized drug to the bronchial tree. To study the influence of various anatomical, physical, and physiological factors on aerosol delivery in preterm newborns, it is crucial to have appropriate in vitro models, which are currently not available. We therefore constructed the premature infant nose throat-model (PrINT-Model), an upper airway model corresponding to a premature infant of 32-wk gestational age by three-dimensional (3D) reconstruction of a three-planar magnetic resonance imaging scan and subsequent 3D-printing. Validation was realized by visual comparison and comparison of total airway volume. To study the feasibility of measuring aerosol deposition, budesonide was aerosolized through the cast and lung dose was expressed as percentage of nominal dose. The airway volumes of the initial magnetic resonance imaging and validation computed tomography scan showed a relative deviation of 0.94%. Lung dose at low flow (1 L/min) was 61.84% and 9.00% at high flow (10 L/min), p < 0.0001. 3D-reconstruction provided an anatomically accurate surrogate of the upper airways of a 32-wk-old premature infant, making the model suitable for future in vitro testing.

The impact of different nanoparticle surface chemistry and size on uptake and toxicity in a murine macrophage cell line

This study investigated the uptake, kinetics and cellular distribution of different surface coated quantum dots (QDs) before relating this to their toxicity. J774.A1 cells were treated with organic, COOH and NH2 (PEG) surface coated QDs (40 nM). Model 20 nm and 200 nm COOH-modified coated polystyrene beads (PBs) were also examined (50 microg ml(-1)). The potential for uptake of QDs was examined by both fixed and live cell confocal microscopy as well as by flow cytometry over 2 h. Both the COOH 20 nm and 200 nm PBs were clearly and rapidly taken up by the J774.A1 cells, with uptake of 20 nm PBs being relatively quicker and more extensive. Similarly, COOH QDs were clearly taken up by the macrophages. Uptake of NH2 (PEG) QDs was not detectable by live cell imaging however, was observed following 3D reconstruction of fixed cells, as well as by flow cytometry. Cells treated with organic QDs, monitored by live cell imaging, showed only a small amount of uptake in a relatively small number of cells. This uptake was insufficient to be detected by flow cytometry. Imaging of fixed cells was not possible due to a loss in cell integrity related to cytotoxicity. A significant reduction (p<0.05) in the fluorescent intensity in a cell-free environment was found with organic QDs, NH2 (PEG) QDs, 20 nm and 200 nm PBs at pH 4.0 (indicative of an endosome) after 2 h, suggesting reduced stability. No evidence of exocytosis was found over 2 h. These findings confirm that surface coating has a significant influence on the mode of NP interaction with cells, as well as the subsequent consequences of that interaction.

Electron microscopy of high pressure frozen samples: bridging the gap between cellular ultrastructure and atomic resolution

Transmission electron microscopy has provided most of what is known about the ultrastructural organization of tissues, cells, and organelles. Due to tremendous advances in crystallography and magnetic resonance imaging, almost any protein can now be modeled at atomic resolution. To fully understand the workings of biological "nanomachines" it is necessary to obtain images of intact macromolecular assemblies in situ. Although the resolution power of electron microscopes is on the atomic scale, in biological samples artifacts introduced by aldehyde fixation, dehydration and staining, but also section thickness reduces it to some nanometers. Cryofixation by high pressure freezing circumvents many of the artifacts since it allows vitrifying biological samples of about 200 mum in thickness and immobilizes complex macromolecular assemblies in their native state in situ. To exploit the perfect structural preservation of frozen hydrated sections, sophisticated instruments are needed, e.g., high voltage electron microscopes equipped with precise goniometers that work at low temperature and digital cameras of high sensitivity and pixel number. With them, it is possible to generate high resolution tomograms, i.e., 3D views of subcellular structures. This review describes theory and applications of the high pressure cryofixation methodology and compares its results with those of conventional procedures. Moreover, recent findings will be discussed showing that molecular models of proteins can be fitted into depicted organellar ultrastructure of images of frozen hydrated sections. High pressure freezing of tissue is the base which may lead to precise models of macromolecular assemblies in situ, and thus to a better understanding of the function of complex cellular structures.

Cord entanglement in monoamniotic twins: 2D and 3D colour Doppler studies

Cord entanglement affects the majority of monoamniotic (MA) twins, accounting for the high proportion of intrauterine deaths of MA twins, and it is often present from early gestation. 3D ultrasound can be used to acquire volume data comprising information on umbilical colour Doppler flow, providing a very graphic depiction of cord entanglement. We have used 2D, "conventional" and a novel 3D display of colour Doppler ultrasound showing cord entanglement.

A comparison between two-dimensional and three-dimensional cephalometry on frontal radiographs and on cone beam computed tomography scans of human skulls

The aim of this study was to evaluate whether measurements performed on conventional frontal radiographs are comparable to measurements performed on three-dimensional (3D) models of human skulls derived from cone beam computed tomography (CBCT) scans and if the latter can be used in longitudinal studies. Cone beam computed tomography scans and conventional frontal cephalometric radiographs were made of 40 dry human skulls. From the CBCT scan a 3D model was constructed. Standard cephalometric software was used to identify landmarks and to calculate ratios and angles. The same operator identified 10 landmarks on both types of cephalometric radiographs, and on all images, five times with a time interval of 1 wk. Intra-observer reliability was acceptable for all measurements. There was a statistically significant and clinically relevant difference between measurements performed on conventional frontal radiographs and on 3D CBCT-derived models of the same skull. There was a clinically relevant difference between angular measurements performed on conventional frontal cephalometric radiographs, compared with measurements performed on 3D models constructed from CBCT scans. We therefore recommend that 3D models should not be used for longitudinal research in cases where there are only two-dimensional (2D) records from the past.

Tracking of industrial objects by using CAD models

In this paper we present a model-based approach for real-time camera pose estimation in industrial scenarios. The line model which is used for tracking is generated by rendering a polygonal model and extracting contours out of the rendered scene. By un-projecting a point on the contour with the depth value stored in the z-buffer, the 3D coordinates of the contour can be calculated. For establishing 2D/3D correspondences the 3D control points on the contour are projected into the image and a perpendicular search for gradient maxima for every point on the contour is performed. Multiple hypotheses of 2D image points corresponding to a 3D control point make the pose estimation robust against ambiguous edges in the image.

Fitting 3D morphable models using implicit representations

We consider the problem of approximating the 3D scan of a real object through an affine combination of examples. Common approaches depend either on the explicit estimation of point-to-point correspondences or on 2-dimensional projections of the target mesh; both present drawbacks. We follow an approach similar to [IF03] by representing the target via an implicit function, whose values at the vertices of the approximation are used to define a robust cost function. The problem is approached in two steps, by approximating first a coarse implicit representation of the whole target, and then finer, local ones; the local approximations are then merged together with a Poisson-based method. We report the results of applying our method on a subset of 3D scans from the Face Recognition Grand Challenge v.1.0.

3D-Druck von Kunststoff-Medizinprodukten

Das Additive Manufacturing gewinnt im Bereich der Medizintechnik zur Herstellung von Prototypen bis hin zu Endprodukten zunehmend an Bedeutung. Ein großes Hemmnis stellen allerdings die relativ hohen Fertigungskosten dar. Hier bietet der verstärkte Einsatz der 3D-Drucktechnologie (3D Printing) ein erhebliches Potential zur Reduktion der Kosten. Aus dieser Motivation heraus wurde ein 3D-Druckverfahren zur Herstellung biokompatibler, sterilisierbarer Kunststoffmodelle entwickelt. Beim 3D-Druck-Verfahren handelt es sich um einen pulverbasierten Prozess zur schichtweisen Herstellung von Modellen direkt aus Computerdaten. Dabei werden dünne Schichten eines Pulvers auf eine Grundplatte aufgebracht, die dann durch gezielte Binderzugabe entsprechend des aktuellen Bauteilquerschnitts verfestigt werden. Ausgangsmaterial für diesen Prozess ist ein Granulatgemisch auf Basis von PMMA (Polymethylmethacrylat). Als Binderflüssigkeit wird ein Lösungsmittel eingesetzt. Die 3D gedruckten Modelle werden nach einer entsprechenden Trocknungszeit im Pulverbett entpackt und warmgelagert, um das Abdampfen des Lösungsmittels zu beschleunigen. Der Nachweis der Biokompatibilität der hergestellten Modelle erfolgte durch einen Test nach DIN EN ISO 10993-5. In Kooperation mit Anwendern wurden verschiedene Anwendungsbeispiele wie Bohrschablonen, Otoplastiken, Gebissmodelle und Modelle für die präoperative Planung realisiert und charakterisiert.

A complementary radiographic projection of the equine temporomandibular joint

The complexity of the equine skull makes the temporomandibular joint a difficult area to evaluate radiographically. The goal of this study was to determine the optimal angle for a complementary radiographic projection of the equine temporomandibular joint based on a computed tomography (CT) cadaver study. CT was performed on six equine cadaver heads of horses that were euthanized for other reasons than temporomandibular joint disease. After the CT examination, 3D reconstruction of the equine skull was performed to subjectively determine the angle for a complementary radiographic projection of the temporomandibular joint. The angle was measured on the left and right temporomandibular joint of each head. Based on the measurements obtained from the CT images, a radiographic projection of the temporomandibular joint in a rostra-145 degrees ventral-caudodorsal oblique (R45 degrees V-CdDO) direction was developed by placing the X-ray unit 30 degrees laterally, maintaining at the same time the R45 degrees V-CdDO angle (R45 degrees V30 degrees L-CdDLO). This radiographic projection was applied to all cadaver heads and on six live horses. In three of the live horses abnormal findings associated with the temporomandibular joint were detected. We conclude that this new radiographic projection of the temporomandibular joint provides superior visualization of the temporomandibular joint space and the articular surface of the mandibular condyle.

Comparison of arterial blood pressure measurements and hypertension scores obtained by use of three indirect measurement devices in hospitalized dogs

OBJECTIVE: To evaluate the agreement of blood pressure measurements and hypertension scores obtained by use of 3 indirect arterial blood pressure measurement devices in hospitalized dogs. Design-Diagnostic test evaluation. ANIMALS: 29 client-owned dogs. PROCEDURES: 5 to 7 consecutive blood pressure readings were obtained from each dog on each of 3 occasions with a Doppler ultrasonic flow detector, a standard oscillometric device (STO), and a high-definition oscillometric device (HDO). RESULTS: When the individual sets of 5 to 7 readings were evaluated, the coefficient of variation for systolic arterial blood pressure (SAP) exceeded 20% for 0% (Doppler), 11 % (STO), and 28% (HDO) of the sets of readings. After readings that exceeded a 20% coefficient of variation were discarded, repeatability was within 25 (Doppler), 37 (STO), and 39 (HDO) mm Hg for SAP. Correlation of mean values among the devices was between 0.47 and 0.63. Compared with Doppler readings, STO underestimated and HDO overestimated SAP. Limits of agreement between mean readings of any 2 devices were wide. With the hypertension scale used to score SAP, the intraclass correlation of scores was 0.48. Linear-weighted inter-rater reliability between scores was 0.40 (Doppler vs STO), 0.38 (Doppler vs HDO), and 0.29 (STO vs HDO). CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested that no meaningful clinical comparison can be made between blood pressure readings obtained from the same dog with different indirect blood pressure measurement devices.

Ridge alterations post-extraction in the esthetic zone: a 3D analysis with CBCT

Dimensional alterations of the facial bone wall following tooth extractions in the esthetic zone have a profound effect on treatment outcomes. This prospective study in 39 patients is the first to investigate three-dimensional (3D) alterations of facial bone in the esthetic zone during the initial 8 wks following flapless tooth extraction. A novel 3D analysis was carried out, based on 2 consecutive cone beam computed tomographies (CBCTs). A risk zone for significant bone resorption was identified in central areas, whereas proximal areas yielded only minor changes. Correlation analysis identified a facial bone wall thickness of ≤ 1 mm as a critical factor associated with the extent of bone resorption. Thin-wall phenotypes displayed pronounced vertical bone resorption, with a median bone loss of 7.5 mm, as compared with thick-wall phenotypes, which decreased by only 1.1 mm. For the first time, 3D analysis has allowed for documentation of dimensional alterations of the facial bone wall in the esthetic zone of humans following extraction. It also characterized a risk zone prone to pronounced bone resorption in thin-wall phenotypes. Vertical bone loss was 3.5 times more severe than findings reported in the existing literature.

Quantification of Popliteal Artery Deformation During Leg Flexion in Subjects With Peripheral Artery Disease: A Pilot Study

Purpose: To quantify the in vivo deformations of the popliteal artery during leg flexion in subjects with clinically relevant peripheral artery disease (PAD). Methods: Five patients (4 men; mean age 69 years, range 56–79) with varying calcification levels of the popliteal artery undergoing endovascular revascularization underwent 3-dimensional (3D) rotational angiography. Image acquisition was performed with the leg straight and with a flexion of 70°/20° in the knee/hip joints. The arterial centerline and the corresponding branches in both positions were segmented to create 3D reconstructions of the arterial trees. Axial deformation, twisting, and curvatures were quantified. Furthermore, the relationships between the calcification levels and the deformations were investigated. Results: An average shortening of 5.9%±2.5% and twist rate of 3.8±2.2°/cm in the popliteal artery were observed. Maximal curvatures in the straight and flexed positions were 0.12±0.04 cm−1 and 0.24±0.09 cm−1, respectively. As the severity of calcification increased, the maximal curvature in the straight position increased from 0.08 to 0.17 cm−1, while an increase from 0.17 to 0.39 cm−1 was observed for the flexed position. Axial elongations and arterial twisting were not affected by the calcification levels. Conclusion: The popliteal artery of patients with symptomatic PAD is exposed to significant deformations during flexion of the knee joint. The severity of calcification directly affects curvature, but not arterial length or twisting angles. This pilot study also showed the ability of rotational angiography to quantify the 3D deformations of the popliteal artery in patients with various levels of calcification.

Accident or homicide - virtual crime scene reconstruction using 3D methods

The analysis and reconstruction of forensically relevant events, such as traffic accidents, criminal assaults and homicides are based on external and internal morphological findings of the injured or deceased person. For this approach high-tech methods are gaining increasing importance in forensic investigations. The non-contact optical 3D digitising system GOM ATOS is applied as a suitable tool for whole body surface and wound documentation and analysis in order to identify injury-causing instruments and to reconstruct the course of event. In addition to the surface documentation, cross-sectional imaging methods deliver medical internal findings of the body. These 3D data are fused into a whole body model of the deceased. Additional to the findings of the bodies, the injury inflicting instruments and incident scene is documented in 3D. The 3D data of the incident scene, generated by 3D laser scanning and photogrammetry, is also included into the reconstruction. Two cases illustrate the methods. In the fist case a man was shot in his bedroom and the main question was, if the offender shot the man intentionally or accidentally, as he declared. In the second case a woman was hit by a car, driving backwards into a garage. It was unclear if the driver drove backwards once or twice, which would indicate that he willingly injured and killed the woman. With this work, we demonstrate how 3D documentation, data merging and animation enable to answer reconstructive questions regarding the dynamic development of patterned injuries, and how this leads to a real data based reconstruction of the course of event.

Cryo-electron tomography of Kaposi's sarcoma-associated herpesvirus capsids reveals dynamic scaffolding structures essential to capsid assembly and maturation.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a recently discovered DNA tumor virus that belongs to the gamma-herpesvirus subfamily. Though numerous studies on KSHV and other herpesviruses, in general, have revealed much about their multilayered organization and capsid structure, the herpesvirus capsid assembly and maturation pathway remains poorly understood. Structural variability or irregularity of the capsid internal scaffolding core and the lack of adequate tools to study such structures have presented major hurdles to earlier investigations employing more traditional cryo-electron microscopy (cryoEM) single particle reconstruction. In this study, we used cryo-electron tomography (cryoET) to obtain 3D reconstructions of individual KSHV capsids, allowing direct visualization of the capsid internal structures and systematic comparison of the scaffolding cores for the first time. We show that B-capsids are not a structurally homogenous group; rather, they represent an ensemble of "B-capsid-like" particles whose inner scaffolding is highly variable, possibly representing different intermediates existing during the KSHV capsid assembly and maturation. This information, taken together with previous observations, has allowed us to propose a detailed pathway of herpesvirus capsid assembly and maturation.

History of Medicine Schedule 2010-2011

William Osler (1849-1919): America’s Most Famous Physician (Robert E. Rakel) The Assassination of John F. Kennedy: A Neurosurgeon’s Eyewitness Account of the Medical Aspect of the Events of November 22, 1963 (Robert G. Grossman) Making Cancer History: Disease and Discovery at the University of Texas M.D. Anderson Cancer Center (James S. Olson) The History of Pathology as a Biological Science and Medical Specialty (L. Maximillian Buja) “Medicine in the Mid-19th Century America” (Student Essay Contest Winner) (David Hunter) The Achievements and Enduring Relevance of Rudolph Virchow (Nathan Grohmann) Medicine: Perspectives in History and Art (Robert E. Greenspan) What Every Physician Should Know: Lessons from the Past (Robert E. Greenspan) Medicine in Ancient Mesopotamia (Sajid Haque) The History of Texas Children’s Hospital (B. Lee Ligon) Visualizing Disease: Motion Pictures in the History of Medical Education (Kirsten Ostherr)