Concise reviews: in vitro-produced pancreas organogenesis models in three dimensions: self-organization from few stem cells or progenitors.

Three-dimensional models of organ biogenesis have recently flourished. They promote a balance between stem/progenitor cell expansion and differentiation without the constraints of flat tissue culture vessels, allowing for autonomous self-organization of cells. Such models allow the formation of miniature organs in a dish and are emerging for the pancreas, starting from embryonic progenitors and adult cells. This review focuses on the currently available systems and how these allow new types of questions to be addressed. We discuss the expected advancements including their potential to study human pancreas development and function as well as to develop diabetes models and therapeutic cells.

Morphodynamic analysis of cerebral aneurysm pulsation from time-resolved rotational angiography

This paper presents a technique to estimate and model patient-specific pulsatility of cerebral aneurysms over onecardiac cycle, using 3D rotational X-ray angiography (3DRA) acquisitions. Aneurysm pulsation is modeled as a time varying-spline tensor field representing the deformation applied to a reference volume image, thus producing the instantaneousmorphology at each time point in the cardiac cycle. The estimated deformation is obtained by matching multiple simulated projections of the deforming volume to their corresponding original projections. A weighting scheme is introduced to account for the relevance of each original projection for the selected time point. The wide coverage of the projections, together with the weighting scheme, ensures motion consistency in all directions. The technique has been tested on digital and physical phantoms that are realistic and clinically relevant in terms of geometry, pulsation and imaging conditions. Results from digital phantomexperiments demonstrate that the proposed technique is able to recover subvoxel pulsation with an error lower than 10% of the maximum pulsation in most cases. The experiments with the physical phantom allowed demonstrating the feasibility of pulsation estimation as well as identifying different pulsation regions under clinical conditions.

Assessment of volumetric bone mineral density of the femoral neck in postmenopausal women with and without vertebral fractures using quantitative multi-slice CT.

OBJECTIVE: To demonstrate the validity and reliability of volumetric quantitative computed tomography (vQCT) with multi-slice computed tomography (MSCT) and dual energy X-ray absorptiometry (DXA) for hip bone mineral density (BMD) measurements, and to compare the differences between the two techniques in discriminating postmenopausal women with osteoporosis-related vertebral fractures from those without. METHODS: Ninety subjects were enrolled and divided into three groups based on the BMD values of the lumbar spine and/or the femoral neck by DXA. Groups 1 and 2 consisted of postmenopausal women with BMD changes <-2SD, with and without radiographically confirmed vertebral fracture (n=11 and 33, respectively). Group 3 comprised normal controls with BMD changes > or =-1SD (n=46). Post-MSCT (GE, LightSpeed16) scan reconstructed images of the abdominal-pelvic region, 1.25 mm thick per slice, were processed by OsteoCAD software to calculate the following parameters: volumetric BMD values of trabecular bone (TRAB), cortical bone (CORT), and integral bone (INTGL) of the left femoral neck, femoral neck axis length (NAL), and minimum cross-section area (mCSA). DXA BMD measurements of the lumbar spine (AP-SPINE) and the left femoral neck (NECK) also were performed for each subject. RESULTS: The values of all seven parameters were significantly lower in subjects of Groups 1 and 2 than in normal postmenopausal women (P<0.05, respectively). Comparing Groups 1 and 2, 3D-TRAB and 3D-INTGL were significantly lower in postmenopausal women with vertebral fracture(s) [(109.8+/-9.61) and (243.3+/-33.0) mg/cm3, respectively] than in those without [(148.9+/-7.47) and (285.4+/-17.8) mg/cm(3), respectively] (P<0.05, respectively), but no significant differences were evident in AP-SPINE or NECK BMD. CONCLUSION: the femoral neck-derived volumetric BMD parameters using vQCT appeared better than the DXA-derived ones in discriminating osteoporotic postmenopausal women with vertebral fractures from those without. vQCT might be useful to evaluate the effect of osteoporotic vertebral fracture status on changes in bone mass in the femoral neck.

Comparison between standard radiography and spiral CT with 3D reconstruction in the evaluation, classification and management of tibial plateau fractures.

The aim of this study was to compare the diagnostic efficiency of plain film and spiral CT examinations with 3D reconstructions of 42 tibial plateau fractures and to assess the accuracy of these two techniques in the pre-operative surgical plan in 22 cases. Forty-two tibial plateau fractures were examined with plain film (anteroposterior, lateral, two obliques) and spiral CT with surface-shaded-display 3D reconstructions. The Swiss AO-ASIF classification system of bone fracture from Muller was used. In 22 cases the surgical plans and the sequence of reconstruction of the fragments were prospectively determined with both techniques, successively, and then correlated with the surgical reports and post-operative plain film. The fractures were underestimated with plain film in 18 of 42 cases (43%). Due to the spiral CT 3D reconstructions, and precise pre-operative information, the surgical plans based on plain film were modified and adjusted in 13 cases among 22 (59%). Spiral CT 3D reconstructions give a better and more accurate demonstration of the tibial plateau fracture and allows a more precise pre-operative surgical plan.

Body surface area and body weight predict total liver volume in Western adults.

Computed tomography (CT) is used increasingly to measure liver volume in patients undergoing evaluation for transplantation or resection. This study is designed to determine a formula predicting total liver volume (TLV) based on body surface area (BSA) or body weight in Western adults. TLV was measured in 292 patients from four Western centers. Liver volumes were calculated from helical computed tomographic scans obtained for conditions unrelated to the hepatobiliary system. BSA was calculated based on height and weight. Each center used a different established method of three-dimensional volume reconstruction. Using regression analysis, measurements were compared, and formulas correlating BSA or body weight to TLV were established. A linear regression formula to estimate TLV based on BSA was obtained: TLV = -794.41 + 1,267.28 x BSA (square meters; r(2) = 0.46; P &lt;.0001). A formula based on patient weight also was derived: TLV = 191.80 + 18.51 x weight (kilograms; r(2) = 0.49; P &lt;.0001). The newly derived TLV formula based on BSA was compared with previously reported formulas. The application of a formula obtained from healthy Japanese individuals underestimated TLV. Two formulas derived from autopsy data for Western populations were similar to the newly derived BSA formula, with a slight overestimation of TLV. In conclusion, hepatic three-dimensional volume reconstruction based on helical CT predicts TLV based on BSA or body weight. The new formulas derived from this correlation should contribute to the estimation of TLV before liver transplantation or major hepatic resection.

Anatomie du foie: ce qu'il faut savoir [Anatomy of the liver: what you need to know]

A precise knowledge of arterial, portal, hepatic and biliary anatomical variations is mandatory when a liver intervention is planned. However, only certain variations must be searched when a precise intervention is planned. The basic liver anatomy as well as the most relevant malformations will be precised.

Virtual autopsy with multiphase postmortem computed tomographic angiography versus traditional medical autopsy to investigate unexpected deaths of hospitalized patients: a cohort study.

BACKGROUND: "Virtual" autopsy by postmortem computed tomography (PMCT) can replace medical autopsy to a certain extent but has limitations for cardiovascular diseases. These limitations might be overcome by adding multiphase PMCT angiography. OBJECTIVE: To compare virtual autopsy by multiphase PMCT angiography with medical autopsy. DESIGN: Prospective cohort study. (ClinicalTrials.gov: NCT01541995) SETTING: Single-center study at the University Medical Center Hamburg-Eppendorf, Hamburg, Germany, between 1 April 2012 and 31 March 2013. PATIENTS: Hospitalized patients who died unexpectedly or within 48 hours of an event necessitating cardiopulmonary resuscitation. MEASUREMENTS: Diagnoses from clinical records were compared with findings from both types of autopsy. New diagnoses identified by autopsy were classified as major or minor, depending on whether they would have altered clinical management. RESULTS: Of 143 eligible patients, 50 (35%) had virtual and medical autopsy. Virtual autopsy confirmed 93% of all 336 diagnoses identified from antemortem medical records, and medical autopsy confirmed 80%. In addition, virtual and medical autopsy identified 16 new major and 238 new minor diagnoses. Seventy-three of the virtual autopsy diagnoses, including 32 cases of coronary artery stenosis, were identified solely by multiphase PMCT angiography. Of the 114 clinical diagnoses classified as cardiovascular, 110 were confirmed by virtual autopsy and 107 by medical autopsy. In 11 cases, multiphase PMCT angiography showed "unspecific filling defects," which were not reported by medical autopsy. LIMITATION: These results come from a single center with concerted interest and expertise in postmortem imaging; further studies are thus needed for generalization. CONCLUSION: In cases of unexpected death, the addition of multiphase PMCT angiography increases the value of virtual autopsy, making it a feasible alternative for quality control and identification of diagnoses traditionally made by medical autopsy. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.

The influence of drugs used in cardiac anaesthesia and critical care on multiple electrode aggregometry: an in-vitro volunteer study.

BACKGROUND: Multiple electrode aggregometry (MEA) is a point-of-care test evaluating platelet function and the efficacy of platelet inhibitors. In MEA, electrical impedance of whole blood is measured after addition of a platelet activator. Reduced impedance implies platelet dysfunction or the presence of platelet inhibitors. MEA plays an increasingly important role in the management of perioperative platelet dysfunction. In vitro, midazolam, propofol, lidocaine and magnesium have known antiplatelet effects and these may interfere with MEA interpretation. OBJECTIVE: To evaluate the extent to which MEA is modified in the presence of these drugs. DESIGN: An in-vitro study using blood collected from healthy volunteers. SETTING: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 2010 to 2011. PATIENTS: Twenty healthy volunteers. INTERVENTION: Measurement of baseline MEA was using four activators: arachidonic acid, ADP, TRAP-6 and collagen. The study drugs were then added in three increasing, clinically relevant concentrations. MAIN OUTCOME MEASURE: MEA was compared with baseline for each study drug. RESULTS: Midazolam, propofol and lidocaine showed no effect on MEA at any concentration. Magnesium at 2.5 mmol l had a significant effect on the ADP and TRAP tests (31 ± 13 and 96 ± 39 AU, versus 73 ± 21 and 133 ± 28 AU at baseline, respectively), and a less pronounced effect at 1 mmol l on the ADP test (39 ± 0 AU). CONCLUSION: Midazolam, propofol and lidocaine do not interfere with MEA measurement. In patients treated with high to normal doses of magnesium, MEA results for ADP and TRAP-tests should be interpreted with caution. TRIAL REGISTRATION: Clinicaltrials.gov (no. NCT01454427).

Focused ion beam scanning electron microscopy in biology.

Since the end of the last millennium, the focused ion beam scanning electron microscopy (FIB-SEM) has progressively found use in biological research. This instrument is a scanning electron microscope (SEM) with an attached gallium ion column and the 2 beams, electrons and ions (FIB) are focused on one coincident point. The main application is the acquisition of three-dimensional data, FIB-SEM tomography. With the ion beam, some nanometres of the surface are removed and the remaining block-face is imaged with the electron beam in a repetitive manner. The instrument can also be used to cut open biological structures to get access to internal structures or to prepare thin lamella for imaging by (cryo-) transmission electron microscopy. Here, we will present an overview of the development of FIB-SEM and discuss a few points about sample preparation and imaging.

In vivo imaging of T cell delivery to tumors after adoptive transfer therapy.

Adoptive transfer therapy of in vitro-expanded tumor-specific cytolytic T lymphocytes (CTLs) can mediate objective cancer regression in patients. Yet, technical limitations hamper precise monitoring of posttherapy T cell responses. Here we show in a mouse model that fused single photon emission computed tomography and x-ray computed tomography allows quantitative whole-body imaging of (111)In-oxine-labeled CTLs at tumor sites. Assessment of CTL localization is rapid, noninvasive, three-dimensional, and can be repeated for longitudinal analyses. We compared the effects of lymphodepletion before adoptive transfer on CTL recruitment and report that combined treatment increased intratumoral delivery of CTLs and improved antitumor efficacy. Because (111)In-oxine is a Food and Drug Administration-approved clinical agent, and human SPECT-CT systems are available, this approach should be clinically translatable, insofar as it may assess the efficacy of immunization procedures in individual patients and lead to development of more effective therapies.

Enhanced electron-electron correlations in nanometric epitaxial SrRuO3 epitaxial films

Epitaxial and fully strained SrRuO3 thin films have been grown on SrTiO3(100). At initial stages the growth mode is three-dimensional- (3D-)like, leading to a finger-shaped structure aligned with the substrate steps and that eventually evolves into a 2D step-flow growth. We study the impact that the defect structure associated with this unique growth mode transition has on the electronic properties of the films. Detailed analysis of the transport properties of nanometric films reveals that microstructural disorder promotes a shortening of the carrier mean free path. Remarkably enough, at low temperatures, this results in a reinforcement of quantum corrections to the conductivity as predicted by recent models of disordered, strongly correlated electronic systems. This finding may provide a simple explanation for the commonly observed¿in conducting oxides-resistivity minima at low temperature. Simultaneously, the ferromagnetic transition occurring at about 140 K, becomes broader as film thickness decreases down to nanometric range. The relevance of these results for the understanding of the electronic properties of disordered electronic systems and for the technological applications of SrRuO3¿and other ferromagnetic and metallic oxides¿is stressed.

Bi-planar 2D-to-3D registration in Fourier domain for stereoscopic X-ray motion tracking

In this paper we present a new method to track bonemovements in stereoscopic X-ray image series of the kneejoint. The method is based on two different X-ray imagesets: a rotational series of acquisitions of the stillsubject knee that will allow the tomographicreconstruction of the three-dimensional volume (model),and a stereoscopic image series of orthogonal projectionsas the subject performs movements. Tracking the movementsof bones throughout the stereoscopic image series meansto determine, for each frame, the best pose of everymoving element (bone) previously identified in the 3Dreconstructed model. The quality of a pose is reflectedin the similarity between its simulated projections andthe actual radiographs. We use direct Fourierreconstruction to approximate the three-dimensionalvolume of the knee joint. Then, to avoid the expensivecomputation of digitally rendered radiographs (DRR) forpose recovery, we reformulate the tracking problem in theFourier domain. Under the hypothesis of parallel X-raybeams, we use the central-slice-projection theorem toreplace the heavy 2D-to-3D registration of projections inthe signal domain by efficient slice-to-volumeregistration in the Fourier domain. Focusing onrotational movements, the translation-relevant phaseinformation can be discarded and we only consider scalarFourier amplitudes. The core of our motion trackingalgorithm can be implemented as a classical frame-wiseslice-to-volume registration task. Preliminary results onboth synthetic and real images confirm the validity ofour approach.

Detection and Characterization of Preferential Flow Paths in the Downstream Area of a Hazardous Landfill

We have used surface-based electrical resistivity tomography to detect and characterize preferential hydraulic pathways in the immediate downstream area of an abandoned, hazardous landfill. The landfill occupies the void left by a former gravel pit and its base is close to the groundwater table and lacking an engineered barrier. As such, this site is remarkably typical of many small- to medium-sized waste deposits throughout the densely populated and heavily industrialized foreland on both sides of the Alpine arc. Outflows of pollutants lastingly contaminated local drinking water supplies and necessitated a partial remediation in the form of a synthetic cover barrier, which is meant to prevent meteoric water from percolating through the waste before reaching the groundwater table. Any future additional isolation of the landfill in the form of lateral barriers thus requires adequate knowledge of potential preferential hydraulic pathways for outflowing contaminants. Our results, inferred from a suite of tomographically inverted surfaced-based electrical resistivity profiles oriented roughly perpendicular to the local hydraulic gradient, indicate that potential contaminant outflows would predominantly occur along an unexploited lateral extension of the original gravel deposit. This finds its expression as a distinct and laterally continuous high-resistivity anomaly in the resistivity tomograms. This interpretation is ground-truthed through a litholog from a nearby well. Since the probed glacio-fluvial deposits are largely devoid of mineralogical clay, the geometry of hydraulic and electrical pathways across the pore space of a given lithological unit can be assumed to be identical, which allows for an order-of-magnitude estimation of the overall permeability structure. These estimates indicate that the permeability of the imaged extension of the gravel body is at least two to three orders-of-magnitude higher than that of its finer-grained embedding matrix. This corroborates the preeminent role of the high-resistivity anomaly as a potential preferential flow path.

Zonation for 3D aquifer characterization based on joint inversions of multimethod crosshole geophysical data

Predictive groundwater modeling requires accurate information about aquifer characteristics. Geophysical imaging is a powerful tool for delineating aquifer properties at an appropriate scale and resolution, but it suffers from problems of ambiguity. One way to overcome such limitations is to adopt a simultaneous multitechnique inversion strategy. We have developed a methodology for aquifer characterization based on structural joint inversion of multiple geophysical data sets followed by clustering to form zones and subsequent inversion for zonal parameters. Joint inversions based on cross-gradient structural constraints require less restrictive assumptions than, say, applying predefined petro-physical relationships and generally yield superior results. This approach has, for the first time, been applied to three geophysical data types in three dimensions. A classification scheme using maximum likelihood estimation is used to determine the parameters of a Gaussian mixture model that defines zonal geometries from joint-inversion tomograms. The resulting zones are used to estimate representative geophysical parameters of each zone, which are then used for field-scale petrophysical analysis. A synthetic study demonstrated how joint inversion of seismic and radar traveltimes and electrical resistance tomography (ERT) data greatly reduces misclassification of zones (down from 21.3% to 3.7%) and improves the accuracy of retrieved zonal parameters (from 1.8% to 0.3%) compared to individual inversions. We applied our scheme to a data set collected in northeastern Switzerland to delineate lithologic subunits within a gravel aquifer. The inversion models resolve three principal subhorizontal units along with some important 3D heterogeneity. Petro-physical analysis of the zonal parameters indicated approximately 30% variation in porosity within the gravel aquifer and an increasing fraction of finer sediments with depth.