Do mature pulmonary lobes grow after transplantation into an immature recipient?

BACKGROUND The use of reduced-size adult lung transplants could help solve the profound pediatric donor lung shortage. However, adequate long-term function of the mature grafts requires growth in proportion to the recipient's development. METHODS Mature left lower lobes from adult mini-pigs (age: 7 months; mean body weight: 30 kg) were transplanted into 14-week-old piglets (mean body weight: 15 kg). By the end of the 14-week holding period, lungs of the recipients (n = 4) were harvested. After volumetric measurements, the lung morphology was studied using light microscopy, scanning, and transmission electron microscopy. Changes of alveolar airspace volume were determined using a computer aided image analysis system. Comparisons were made to age- and weight-matched controls. RESULTS Volumetric studies showed no significant differences (p = 0.49) between the specific volume (mL/kg body weight) of lobar grafts and left lower lobes of adult controls. Morphologic studies showed marked structural differences between the grafts and the right native lungs of the recipients, with increased average alveolar diameter of the grafts. On light microscopy and scanning electron microscopy, alveoli appeared dilated and rounded compared to the normal polygonal shape in the controls. The computer generated semi-quantitative data of relative alveolar airspace volume tended to be higher in transplanted lobes. CONCLUSIONS The mature pulmonary lobar grafts have filled the growing left hemithorax of the developing recipient. Emphysema-like alterations of the grafts were observed without evidence of alveolar growth in the mature lobar transplants. Thus, it can be questioned whether mature pulmonary grafts can guarantee sufficient long-term gas exchange in growing recipients.

Noble gas, CFC and other geochemical evidence for the age and origin of the Bath thermal waters, UK

The city of Bath is a World Heritage site and its thermal waters, the Roman Baths and new spa development rely on undisturbed flow of the springs (45 °C). The current investigations provide an improved understanding of the residence times and flow regime as basis for the source protection. Trace gas indicators including the noble gases (helium, neon, argon, krypton and xenon) and chlorofluorocarbons (CFCs), together with a more comprehensive examination of chemical and stable isotope tracers are used to characterise the sources of the thermal water and any modern components. It is shown conclusively by the use of 39Ar that the bulk of the thermal water has been in circulation within the Carboniferous Limestone for at least 1000 years. Other stable isotope and noble gas measurements confirm previous findings and strongly suggest recharge within the Holocene time period (i.e. the last 12 kyr). Measurements of dissolved 85Kr and chlorofluorocarbons constrain previous indications from tritium that a small proportion (<5%) of the thermal water originates from modern leakage into the spring pipe passing through Mesozoic valley fill underlying Bath. This introduces small amounts of O2 into the system, resulting in the Fe precipitation seen in the King’s Spring. Silica geothermometry indicates that the water is likely to have reached a maximum temperature of between 69–99 °C, indicating a most probable maximum circulation depth of ∼3 km, which is in line with recent geological models. The rise to the surface of the water is sufficiently indirect that a temperature loss of >20 °C is incurred. There is overwhelming evidence that the water has evolved within the Carboniferous Limestone formation, although the chemistry alone cannot pinpoint the geometry of the recharge area or circulation route. For a likely residence time of 1–12 kyr, volumetric calculations imply a large storage volume and circulation pathway if typical porosities of the limestone at depth are used, indicating that much of the Bath-Bristol basin must be involved in the water storage.

Measurements of a water potential and water content in unsaturated crystalline rock

A water desaturation zone develops around a tunnel in water-saturated rock when the evaporative water loss at the rock surface is larger than the water flow from the surrounding saturated region of restricted permeability. We describe the methods with which such water desaturation processes in rock materials can be quantified. The water retention characteristic theta(psi) of crystalline rock samples was determined with a pressure membrane apparatus. The negative water potential, identical to the capillary pressure, psi, below the tensiometric range (psi < -0.1 MPa) can be measured with thermocouple psychrometers (TP), and the volumetric water contents, theta, by means of time domain reflectometry (TDR). These standard methods were adapted for measuring the water status in a macroscopically unfissured granodiorite with a total porosity of approximately 0.01. The measured water retention curve of granodiorite samples from the Grimsel test site (central Switzerland) exhibits a shape which is typical for bimodal pore size distributions. The measured bimodality is probably an artifact of a large surface ratio of solid/voids. The thermocouples were installed without a metallic screen using the cavity drilled into the granodiorite as a measuring chamber. The water potentials observed in a cylindrical granodiorite monolith ranged between -0.1 and -3.0 MPa; those near the wall in a ventilated tunnel between -0.1 and -2.2 MPa. Two types of three-rod TDR Probes were used, one as a depth probe inserted into the rock, the other as a surface probe using three copper stripes attached to the surface for detecting water content changes in the rock-to-air boundary. The TDR signal was smoothed with a low-pass filter, and the signal length determined based on the first derivative of the trace. Despite the low porosity of crystalline rock these standard methods are applicable to describe the unsaturated zone in solid rock and may also be used in other consolidated materials such as concrete.

Gadoxetate uptake as a possible marker of hepatocyte damage after liver resection-preliminary data

AIM: To determine the feasibility of evaluating surgically induced hepatocyte damage using gadoxetate disodium (Gd-EOB-DTPA) as a marker for viable hepatocytes at magnetic resonance imaging (MRI) after liver resection. MATERIAL AND METHODS: Fifteen patients were prospectively enrolled in this institutional review board-approved study prior to elective liver resection after informed consent. Three Tesla MRI was performed 3-7 days after surgery. Three-dimensional (3D) T1-weighted (W) volumetric interpolated breath-hold gradient echo (VIBE) sequences covering the liver were acquired before and 20 min after Gd-EOB-DTPA administration. The signal-to-noise ratio (SNR) was used to compare the uptake of Gd-EOB-DTPA in healthy liver tissue and in liver tissue adjacent to the resection border applying paired Student's t-test. Correlations with potential influencing factors (blood loss, duration of intervention, age, pre-existing liver diseases, postoperative change of resection surface) were calculated using Pearson's correlation coefficient. RESULTS: Before Gd-EOB-DTPA administration the SNR did not differ significantly (p = 0.052) between healthy liver tissue adjacent to untouched liver borders [59.55 ± 25.46 (SD)] and the liver tissue compartment close to the resection surface (63.31 ± 27.24). During the hepatocyte-specific phase, the surgical site showed a significantly (p = 0.04) lower SNR (69.44 ± 24.23) compared to the healthy site (78.45 ± 27.71). Dynamic analyses revealed a significantly lower increase (p = 0.008) in signal intensity in the healthy tissue compared to the resection border compartment. CONCLUSION: EOB-DTPA-enhanced MRI may have the potential to be an effective non-invasive tool for detecting hepatocyte damage after liver resection.

Microstructural Parameters of Bone Evaluated Using HR-pQCT Correlate with the DXA-Derived Cortical Index and the Trabecular Bone Score in a Cohort of Randomly Selected Premenopausal Women.

BACKGROUND Areal bone mineral density is predictive for fracture risk. Microstructural bone parameters evaluated at the appendicular skeleton by high-resolution peripheral quantitative computed tomography (HR-pQCT) display differences between healthy patients and fracture patients. With the simple geometry of the cortex at the distal tibial diaphysis, a cortical index of the tibia combining material and mechanical properties correlated highly with bone strength ex vivo. The trabecular bone score derived from the scan of the lumbar spine by dual-energy X-ray absorptiometry (DXA) correlated ex vivo with the micro architectural parameters. It is unknown if these microstructural correlations could be made in healthy premenopausal women. METHODS Randomly selected women between 20-40 years of age were examined by DXA and HR-pQCT at the standard regions of interest and at customized sub regions to focus on cortical and trabecular parameters of strength separately. For cortical strength, at the distal tibia the volumetric cortical index was calculated directly from HR-pQCT and the areal cortical index was derived from the DXA scan using a Canny threshold-based tool. For trabecular strength, the trabecular bone score was calculated based on the DXA scan of the lumbar spine and was compared with the corresponding parameters derived from the HR-pQCT measurements at radius and tibia. RESULTS Seventy-two healthy women were included (average age 33.8 years, average BMI 23.2 kg/m(2)). The areal cortical index correlated highly with the volumetric cortical index at the distal tibia (R  =  0.798). The trabecular bone score correlated moderately with the microstructural parameters of the trabecular bone. CONCLUSION This study in randomly selected premenopausal women demonstrated that microstructural parameters of the bone evaluated by HR-pQCT correlated with the DXA derived parameters of skeletal regions containing predominantly cortical or cancellous bone. Whether these indexes are suitable for better predictions of the fracture risk deserves further investigation.

Experimental Validation of Finite Element Analysis of Human Vertebral Collapse Under Large Compressive Strains

Osteoporosis-related vertebral fractures represent a major health problem in elderly populations. Such fractures can often only be diagnosed after a substantial deformation history of the vertebral body. Therefore, it remains a challenge for clinicians to distinguish between stable and progressive potentially harmful fractures. Accordingly, novel criteria for selection of the appropriate conservative or surgical treatment are urgently needed. Computer tomography-based finite element analysis is an increasingly accepted method to predict the quasi-static vertebral strength and to follow up this small strain property longitudinally in time. A recent development in constitutive modeling allows us to simulate strain localization and densification in trabecular bone under large compressive strains without mesh dependence. The aim of this work was to validate this recently developed constitutive model of trabecular bone for the prediction of strain localization and densification in the human vertebral body subjected to large compressive deformation. A custom-made stepwise loading device mounted in a high resolution peripheral computer tomography system was used to describe the progressive collapse of 13 human vertebrae under axial compression. Continuum finite element analyses of the 13 compression tests were realized and the zones of high volumetric strain were compared with the experiments. A fair qualitative correspondence of the strain localization zone between the experiment and finite element analysis was achieved in 9 out of 13 tests and significant correlations of the volumetric strains were obtained throughout the range of applied axial compression. Interestingly, the stepwise propagating localization zones in trabecular bone converged to the buckling locations in the cortical shell. While the adopted continuum finite element approach still suffers from several limitations, these encouraging preliminary results towardsthe prediction of extended vertebral collapse may help in assessing fracture stability in future work.

Low Mass Calibration Target for MM-Wave Remote Sensing Instruments

The reliability of millimeter and sub-millimeter wave radiometer measurements is dependent on the accuracy of the loads they employ as calibration targets. In the recent past on-board calibration loads have been developed for a variety of satellite remote sensing instruments. Unfortunately some of these have suffered from calibration inaccuracies which had poor thermal performance of the calibration target as the root cause. Stringent performance parameters of the calibration target such as low reflectivity, high temperature uniformity, low mass and low power consumption combined with low volumetric requirements remain a challenge for the space instrument developer. In this paper we present a novel multi-layer absorber concept for a calibration load which offers an excellent compromise between very good radiometric performance and temperature uniformity and the mass and volumetric constraints required by space-borne calibration targets.

Multi-modal glioblastoma segmentation: man versus machine

BACKGROUND AND PURPOSE Reproducible segmentation of brain tumors on magnetic resonance images is an important clinical need. This study was designed to evaluate the reliability of a novel fully automated segmentation tool for brain tumor image analysis in comparison to manually defined tumor segmentations. METHODS We prospectively evaluated preoperative MR Images from 25 glioblastoma patients. Two independent expert raters performed manual segmentations. Automatic segmentations were performed using the Brain Tumor Image Analysis software (BraTumIA). In order to study the different tumor compartments, the complete tumor volume TV (enhancing part plus non-enhancing part plus necrotic core of the tumor), the TV+ (TV plus edema) and the contrast enhancing tumor volume CETV were identified. We quantified the overlap between manual and automated segmentation by calculation of diameter measurements as well as the Dice coefficients, the positive predictive values, sensitivity, relative volume error and absolute volume error. RESULTS Comparison of automated versus manual extraction of 2-dimensional diameter measurements showed no significant difference (p = 0.29). Comparison of automated versus manual segmentation of volumetric segmentations showed significant differences for TV+ and TV (p<0.05) but no significant differences for CETV (p>0.05) with regard to the Dice overlap coefficients. Spearman's rank correlation coefficients (ρ) of TV+, TV and CETV showed highly significant correlations between automatic and manual segmentations. Tumor localization did not influence the accuracy of segmentation. CONCLUSIONS In summary, we demonstrated that BraTumIA supports radiologists and clinicians by providing accurate measures of cross-sectional diameter-based tumor extensions. The automated volume measurements were comparable to manual tumor delineation for CETV tumor volumes, and outperformed inter-rater variability for overlap and sensitivity.

Increased bone mineral density at the hypoxia prone site of the juxta-articular metacarpal bone in patients with limited systemic sclerosis: a cross-sectional study

OBJECTIVES Low levels of oxygen has been shown to be involved in the induction of osteogenesis, particularly in bone repair. It is unknown whether hypoxia leads to osteogenesis at the hypoxia prone skeletal sites in limited systemic sclerosis. This study determined the total and trabecular volumetric bone mineral density (vBMD) at the hypoxia prone site of the juxta-articular metacarpal bone. METHODS In this cross-sectional study, female patients with limited systemic sclerosis were included and compared to healthy controls. Peripheral quantitative computed tomography was used to measure cross-sectional area, total vBMD, and trabecular vBMD at the radius, the tibia and the third metacarpal bone. Disease severity was assessed by the modified Rodnan Skin Score. RESULTS Twenty consecutive patients were included in the sclerosis group and 20 in the control group. Mean age was 60 years (range 52-68 years), and mean disease duration was 45 months (range 4-156 months). Age, height, and weight were comparable between the groups. The mean modified Rodnan Skin Score was 1.78 (range 0 to 8). The sclerosis group showed both higher total and trabecular vBMD at the distal metacarpal bone (p=0.05 and 0.04, respectively). vBMD of the tibia and radius did not differ in both groups. CONCLUSIONS vBMD at the juxta-articular metacarpal bone in patients with limited systemic sclerosis is increased, possibly due to an alteration in local bone metabolism and hypoxia induced local osteogenesis.

Finite element analysis predicts experimental failure patterns in vertebral bodies loaded via intervertebral discs up to large deformation

Vertebral compression fracture is a common medical problem in osteoporotic individuals. The quantitative computed tomography (QCT)-based finite element (FE) method may be used to predict vertebral strength in vivo, but needs to be validated with experimental tests. The aim of this study was to validate a nonlinear anatomy specific QCT-based FE model by using a novel testing setup. Thirty-seven human thoracolumbar vertebral bone slices were prepared by removing cortical endplates and posterior elements. The slices were scanned with QCT and the volumetric bone mineral density (vBMD) was computed with the standard clinical approach. A novel experimental setup was designed to induce a realistic failure in the vertebral slices in vitro. Rotation of the loading plate was allowed by means of a ball joint. To minimize device compliance, the specimen deformation was measured directly on the loading plate with three sensors. A nonlinear FE model was generated from the calibrated QCT images and computed vertebral stiffness and strength were compared to those measured during the experiments. In agreement with clinical observations, most of the vertebrae underwent an anterior wedge-shape fracture. As expected, the FE method predicted both stiffness and strength better than vBMD (R2 improved from 0.27 to 0.49 and from 0.34 to 0.79, respectively). Despite the lack of fitting parameters, the linear regression of the FE prediction for strength was close to the 1:1 relation (slope and intercept close to one (0.86 kN) and to zero (0.72 kN), respectively). In conclusion, a nonlinear FE model was successfully validated through a novel experimental technique for generating wedge-shape fractures in human thoracolumbar vertebrae.

Radiation dose reduction in postoperative computed position control of cochlear implant electrodes in lambs - An experimental study

OBJECTIVE Cochlear implants (CI) are standard treatment for prelingually deafened children and postlingually deafened adults. Computed tomography (CT) is the standard method for postoperative imaging of the electrode position. CT scans accurately reflect electrode depth and position, which is essential prior to use. However, routine CT examinations expose patients to radiation, which is especially problematic in children. We examined whether new CT protocols could reduce radiation doses while preserving diagnostic accuracy. METHODS To investigate whether electrode position can be assessed by low-dose CT protocols, a cadaveric lamb model was used because the inner ear morphology is similar to humans. The scans were performed at various volumetric CT dose-indexes CTDIvol)/kV combinations. For each constant CTDIvol the tube voltage was varied (i.e., 80, 100, 120 and 140kV). This procedure was repeated at different CTDIvol values (21mGy, 11mGy, 5.5mGy, 2.8mGy and 1.8mGy). To keep the CTDIvol constant at different tube voltages, the tube current values were adjusted. Independent evaluations of the images were performed by two experienced and blinded neuroradiologists. The criteria diagnostic usefulness, image quality and artifacts (scaled 1-4) were assessed in 14 cochlear-implanted cadaveric lamb heads with variable tube voltages. RESULTS Results showed that the standard CT dose could be substantially reduced without sacrificing diagnostic accuracy of electrode position. The assessment of the CI electrode position was feasible in almost all cases up to a CTDIvol of 2-3mGy. The number of artifacts did not increase for images within this dose range as compared to higher dosages. The extent of the artifacts caused by the implanted metal-containing CI electrode does not depend on the radiation dose and is not perceptibly influenced by changes in the tube voltage. Summarizing the evaluation of the CI electrode position is possible even at a very low radiation dose. CONCLUSIONS CT imaging of the temporal bone for postoperative electrode position control of the CI is possible with a very low and significantly radiation dose. The tube current-time product and voltage can be reduced by 50% without increasing artifacts. Low-dose postoperative CT scans are sufficient for localizing the CI electrode.

Improved VMAT planning for head and neck tumors with an advanced optimization algorithm

OBJECTIVE In this study, the "Progressive Resolution Optimizer PRO3" (Varian Medical Systems) is compared to the previous version "PRO2" with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients. MATERIALS AND METHODS For eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms. RESULTS For the phase 1 plans (PD=54Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22±5 Gy with PRO3, as compared to 32±12Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V95%=97±1% could be reached with PRO3, as compared to 86±5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses. CONCLUSION A comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies.

Evaluation of different types of enamel conditioning before application of a fissure sealant

The aim of the study was to compare fissure sealant quality after mechanical conditioning of erbium-doped yttrium aluminium garnet (Er:YAG) laser or air abrasion prior to chemical conditioning of phosphoric acid etching or of a self-etch adhesive. Twenty-five permanent molars were initially divided into three groups: control group (n = 5), phosphoric acid etching; test group 1 (n = 10), air abrasion; and test group 2, (n = 10) Er:YAG laser. After mechanical conditioning, the test group teeth were sectioned buccolingually and the occlusal surface of one half tooth (equal to one sample) was acid etched, while a self-etch adhesive was applied on the other half. The fissure system of each sample was sealed, thermo-cycled and immersed in 5% methylene dye for 24 h. Each sample was sectioned buccolingually, and one slice was analysed microscopically. Using specialized software microleakage, unfilled margin, sealant failure and unfilled area proportions were calculated. A nonparametric ANOVA model was applied to compare the Er:YAG treatment with that of air abrasion and the self-etch adhesive with phosphoric acid (α = 0.05). Test groups were compared to the control group using Wilcoxon rank sum tests (α = 0.05). The control group displayed significantly lower microleakage but higher unfilled area proportions than the Er:YAG laser + self-etch adhesive group and displayed significantly higher unfilled margin and unfilled area proportions than the air-abrasion + self-etch adhesive group. There was no statistically significant difference in the quality of sealants applied in fissures treated with either Er:YAG laser or air abrasion prior to phosphoric acid etching, nor in the quality of sealants applied in fissures treated with either self-etch adhesive or phosphoric acid following Er:YAG or air-abrasion treatment.

Pulmonary lymphangioleiomyomatosis: analysis of disease manifestation by region-based quantification of lung parenchyma

PURPOSE Lymphangioleiomyomatosis (LAM) is characterized by proliferation of smooth muscle tissue that causes bronchial obstruction and secondary cystic destruction of lung parenchyma. The aim of this study was to evaluate the typical distribution of cystic defects in LAM with quantitative volumetric chest computed tomography (CT). MATERIALS AND METHODS CT examinations of 20 patients with confirmed LAM were evaluated with region-based quantification of lung parenchyma. Additionally, 10 consecutive patients were identified who had recently undergone CT imaging of the lung at our institution, in which no pathologies of the lung were found, to serve as a control group. Each lung was divided into three regions (upper, middle and lower thirds) with identical number of slices. In addition, we defined a "peel" and "core" of the lung comprising the 2 cm subpleural space and the remaining inner lung area. Computerized detection of lung volume and relative emphysema was performed with the PULMO 3D software (v3.42, Fraunhofer MEVIS, Bremen, Germany). This software package enables the quantification of emphysematous lung parenchyma by calculating the pixel index, which is defined as the ratio of lung voxels with a density <-950HU to the total number of voxels in the lung. RESULTS Cystic changes accounted for 0.1-39.1% of the total lung volume in patients with LAM. Disease manifestation in the central lung was significantly higher than in peripheral areas (peel median: 15.1%, core median: 20.5%; p=0.001). Lower thirds of lung parenchyma showed significantly less cystic changes than upper and middle lung areas combined (lower third: median 13.4, upper and middle thirds: median 19.0, p=0.001). CONCLUSION The distribution of cystic lesions in LAM is significantly more pronounced in the central lung compared to peripheral areas. There is a significant predominance of cystic changes in apical and intermediate lung zones compared to the lung bases.

Viscous-Flow Approach to In Situ Infiltration and In Vitro Saturated Hydraulic Conductivity Determination

Infiltration is dominantly gravity driven, and a viscous-flow approach was developed. Laminar film flow equilibrates gravity with the viscous force and a constant flow velocity evolves during a period lasting 3/2 times the duration of a constant input rate, qS. Film thickness F and the specific contact area L of the film per unit soil volume are the key parameters. Sprinkler irrigation produced in situ time series of volumetric water contents, θ(z,t), as determined with TDR probes. The wetting front velocity v and the time series of the mobile water content, w(z,t) were deduced from θ(z,t). In vitro steady flow in a core of saturated soil provided volume flux density, q(z,t), and flow velocity, v, as determined from a heat front velocity. The F and L parameters of the in situ and the in vitro experiments were compared. The macropore-flow restriction states that, for a particular permeable medium, the specific contact area L must be independent from qS i.e., dL/dqS = 0. If true, then the relationship of qS ∝ v3/2 could scale a wide range of input rates 0 ≤ qS ≤ saturated hydraulic conductivity, Ksat, into a permeable medium, and kinematic-wave theory would become a versatile tool to deal with non-equilibrium flow. The viscous-flow approach is based on hydromechanical principles similar to Darcy’s law, but currently it is not suited to deduce flow properties from specified individual spatial structures of permeable media.