Martin Obert

Flat-panel volumetric computed tomography: a new method for visualizing fine bone detail in living mice.

In this report, we present a new noninvasive 3-dimensional (3D) imaging technology for in vivo monitoring of the skeletal development of mice: flat-panel volumetric Computed Tomography (fpvCT). Long-term investigations of 4 mice are presented, with up to 14 scans of each mouse from postnatal day 0 to 86. Examinations of a newborn and an adult mouse, performed with fpvCT and clinical multislice CT (MSCT), demonstrate the superior image quality of high-resolution fpvCT.

Ossification Degrees of Cranial Sutures Determined with Flat‐Panel Computed Tomography: Narrowing the Age Estimate with Extrema

Abstract:  Since Broca’s time (1824–1880), ossification of the neurocranial sutures has been used as a characteristic of age. Current approaches include the visual macroscopic examination of ecto and endocranial sutures. The evaluation of the cross‐section of sutures usually necessitates the destruction of the neurocranium. In a nondestructive alternative approach that was tested within the context of the “Digital Forensic Osteology” project that ran in cooperation with the Virtopsy®‐Project, it emerged that the resolution of conventional multi‐slice computed tomography data sets was not high enough to image sutures. Thus for the experiments presented here, the eXplore Locus Ultra flat‐panel computed tomography scanner from GE Healthcare was used. Calottes were scanned during autopsy and then immediately returned to the corpse. So far, the skullcaps of 221 individuals have been scanned. The cross‐sections of 14 suture segments could be assessed for seven previously defined stages of ossification. In a converse step, the 14 highest and lowest age estimate values corresponding to the individual stages of suture closure found were estimated for each calotte. The obtained ranges narrowing down the age estimate were evaluated with statistics. A mean value of 43.31 years for the range of narrowed age estimates shows that this method can be a useful aid in estimating age. The results of intra‐ and inter‐observer tests showed good overall agreement between the findings of three observers. This method is suitable for a nondestructive age estimation and can be used for the entire calotte.

Immunomodulation by fish-oil containing lipid emulsions in murine acute respiratory distress syndrome

IntroductionAcute respiratory distress syndrome (ARDS) is a major cause of mortality in intensive care units. Patients with ARDS often require parenteral nutrition with lipid emulsions as essential components. Besides being an energy supply, these lipid emulsions might display differential modulatory effects on lung integrity and inflammation.MethodsIn a pre-emptive strategy, we investigated the impact of three different intravenously infused lipid emulsions on lung morphology, leukocyte invasion, protein leakage and cytokines in a murine model of ARDS. Mice received an infusion of normal saline solution, a pure long-chain triglycerides (LCT) emulsion, a medium-chain triglycerides (MCT) containing mixed emulsion (LCT/MCT), or a fish oil (FO) containing mixed emulsion (LCT/MCT/FO) before lipopolysaccharide (LPS) challenge.ResultsMice pre-infused with fish oil-containing lipid emulsion showed decreased leukocyte invasion, protein leakage, myeloperoxidase activity, and cytokine production in their alveolar space after LPS challenge compared to mice receiving LCT or LCT/MCT. In line with these findings, lung morphology assessed by histological staining after LPS-induced lung injury improved faster in the LCT/MCT/FO group. Concerning the above mentioned parameters, no significant difference was observed between mice infused with LCT or the combination of LCT and MCT.ConclusionFish oil-containing lipid emulsions might exert anti-inflammatory and pro-resolving effects in the murine model of acute lung injury. Partial replacement of n-6 fatty acids with n-3 fatty acids may thus be of benefit for critically ill patients at risk for ARDS which require parenteral nutrition.

High resolution imaging of craniofacial bone specimens by flat-panel volumetric computed tomography

INTRODUCTION The prototype flat-panel volumetric computed tomograph (fpvCT) provides a new 3D imaging technology with detailed high resolution by using large-area flat-panel X-ray detectors. The object of this study was to evaluate the benefit of high resolution imaging using the experimental fpvCT to visualise different types of human craniofacial bone pathology. The study proved the feasibility of performing an intraoperative evaluation of free margins in bone malignancies using fpvCT. MATERIAL AND METHODS In this study, 35 bone specimens of various pathological types were examined by fpvCT. fpvCT data were compared with pre-operative multislice clinical CT images as well as with post-operative histological findings. RESULTS Bone tumours can be visualised with their specific pathological architecture and infiltration structure faster and more precisely by fpvCT than by multislice CT. The analysis of the resection margins supports the surgical procedure intraoperatively, especially when an immediate reconstruction with bone transplantation is carried out. DISCUSSION The fpvCT has a superior image quality when compared with clinical CT systems. The imaging of the bone structure itself has been shown to be useful for the interpretation of osseous resection borders. Furthermore, it can facilitate the diagnosis of tumour progression, especially in areas that are difficult to access, such as the base of the skull.

High-resolution flat-panel volumetric CT images show no correlation between human age and sagittal suture obliteration—Independent of sex

This study investigated whether digital, high-resolution CT-images of the internal human sagittal suture structure include information that enables a novel method of age at death (aad) determination. To accomplish this, coronal, flat-panel-based volumetric computed tomography (eXplore Locus Ultra scanner) images were automatically analyzed by a software implementation of an algorithm that determines user independent whether a suture is open or closed. 29,205 images of the local vicinity of the sagittal suture of 164 males and 85 females of European descent were investigated separately for both sexes. We used conditional probabilities and a chi(2)-test to investigate whether there is a correlation between aad and suture obliteration or not. The computer-aided analysis enables us to handle huge volumes of data that could not otherwise be analyzed within a reasonable time frame. The implemented algorithm ensured a strongly reproducible, reliable, accurate, and fast differentiation between closed and open sutures. The evaluation of various statistical parameters suggests that there is no reason to assume a correlation between age and suture closure--with equal findings for both sexes. Therefore, we conclude that determination of aad based on the evaluation of sagittal suture obliteration is not possible. This agrees well - thus unsatisfactorily - with the recent literature.

NUMERICAL ESTIMATES OF THE FRACTAL DIMENSION D AND THE LACUNARITY L BY THE MASS RADIUS RELATION

The mass radius relation (mrr) allows the estimation of a local fractal dimension Dl, which depends on a chosen site l of a set, taken as center position for the mrr. We find an unexpected wide range of Dl-values for a numerically analyzed Sierpinski triangle. The analysis of a computer simulation of a biological branching pattern shows rather small Dl-values at the border lines to major empty areas and rather high Dl-values in densely grown regions. The local impression by many Dl of a growth pattern can be interpreted biologically as an inverse measure of, for example, the local immune activity in a living object. We also apply the mrr to investigate the lacunarity L of Cantor dusts. Since numerical difficulties to obtain L are based on the finiteness of a set, we analyze projections of fractals on the unit circle, such that a well-defined largest possible gap size is introduced. The first preliminary results imply rather stable numerical values for L and D for many sets, where D is the average over many Dl. L depends on the size of the smallest details in a set. L is larger if many different gap sizes are given in a generator for a fractal curve as opposed to curves, where only one gap size is given. We assume that a totally different approach has to be set up to obtain L numerically of sets of finite size, since projections of sets or the introduction of periodic boundaries seem inadequate.

A relevant experimental model for human bronchiolitis obliterans syndrome

BACKGROUND The long-term success of human lung transplantation is limited by the development of bronchiolitis obliterans syndrome. Acute rejection episodes and infections are important risk factors and seem to play major pathogenic roles. We established a relevant experimental model that mimics important aspects of human bronchiolitis obliterans syndrome. METHODS The Fischer 344-to-Lewis rat strain combination was used for orthotopic left lung transplantation. Isogeneic transplantations were performed in the Lewis rat. Recipients were treated with ciclosporin for 10 days. Lipopolysaccharide or vehicle was instilled into the airways 28 days after transplantation. Grafts were monitored by computed tomography, and recipients were euthanized on Days 28-90. The messenger RNA expression of selected chemokines and their receptors was measured on Days 28, 29, 33, 40 after transplantation. Graft histopathology on Day 90 was compared with lungs from patients who underwent re-transplantation due to end-stage allograft dysfunction. RESULTS Lung allografts treated with ciclosporin and vehicle only sporadically displayed tissue remodeling. In contrast, lipopolysaccharide treatment induced severe inflammation. In the long-term, severe vascular remodeling, lung fibrosis, and fibroproliferative remodeling of airways were found that closely resemble the histopathologic changes in grafts from human patients with bronchiolitis obliterans syndrome. Chronic damage was virtually absent from pulmonary isografts and native right lungs. Chemokine (C-C motif) ligand 5 and chemokine (C-X-C motif) ligand 9-11, and their receptors, were over-expressed in allografts. CONCLUSIONS Our experimental model mirrors key aspects of human bronchiolitis obliterans syndrome. It will be useful to elucidate its pathogenesis and to develop therapeutic approaches improving the long-term outcome of human lung transplantation.

Aging adult skull remains through radiological density estimates: A comparison of different computed tomography systems and the use of computer simulations to judge the accuracy of results

INTRODUCTION The objective of this article was to explore age-at-death estimates in forensic medicine, which were methodically based on age-dependent, radiologically defined bone-density (HC) decay and which were investigated with a standard clinical computed tomography (CT) system. Such density decay was formerly discovered with a high-resolution flat-panel CT in the skulls of adult females. The development of a standard CT methodology for age estimations--with thousands of installations--would have the advantage of being applicable everywhere, whereas only few flat-panel prototype CT systems are in use worldwide. METHODS A Multi-Slice CT scanner (MSCT) was used to obtain 22,773 images from 173 European human skulls (89 male, 84 female), taken from a population of patients from the Department of Neuroradiology at the University Hospital Giessen and Marburg during 2010 and 2011. An automated image analysis was carried out to evaluate HC of all images. The age dependence of HC was studied by correlation analysis. The prediction accuracy of age-at-death estimates was calculated. Computer simulations were carried out to explore the influence of noise on the accuracy of age predictions. RESULTS Human skull HC values strongly scatter as a function of age for both sexes. Adult male skull bone-density remains constant during lifetime. Adult female HC decays during lifetime, as indicated by a correlation coefficient (CC) of -0.53. Prediction errors for age-at-death estimates for both of the used scanners are in the range of ±18 years at a 75% confidence interval (CI). Computer simulations indicate that this is the best that can be expected for such noisy data. CONCLUSIONS Our results indicate that HC-decay is indeed present in adult females and that it can be demonstrated both by standard and by high-resolution CT methods, applied to different subject groups of an identical population. The weak correlation between HC and age found by both CT methods only enables a method to estimate age-at-death with limited practical relevance since the errors of the estimates are large. Computer simulations clearly indicate that data with less noise and CCs in the order of -0.97 or less would be necessary to enable age-at-death estimates with an accuracy of ±5 years at a 75% CI.

Monitoring of Experimental Rat Lung Transplants by High-Resolution Flat-Panel Volumetric Computer Tomography (fpVCT)

Objective: Noninvasive assessment of experimental lung transplants with high resolution would be favorable to exclude technical failure and to follow up graft outcome in the living animal. Here we describe a flat-panel Volumetric Computed Tomography (fpVCT) technique using a prototype scanner. Methods: Lung transplantation was performed in allogeneic as well as in corresponding syngeneic rat strain combinations. At different time points post-transplantation, fpVCT was performed. Results: Lung transplants can be visualized in the living rat with high-spatial resolution. FpVCT allows a detailed analysis of the lung and the bronchi. Infiltrates developing during rejection episodes can be diagnosed and follow-up studies can easily be performed. Conclusions: With fpVCT it is possible to control the technical success of the surgical procedure. Graft rejection can be visualized individually in the living animal noninvasively, which is highly advantageous for studying the pathogenesis of chronic rejection or to monitor new therapies.

Aging adult skull vaults by applying the concept of fractal geometry to high-resolution computed tomography images

INTRODUCTION Aging human remains is a critical issue in anthropology and forensic medicine, and the search for accurate, new age-estimation methods is ongoing. In our study, we, therefore, explored a new approach to investigate a possible correlation between age-at-death (aad) and geometric irregularities in the bone structure of human skull caps. We applied the concept of fractal geometry and fractal dimension D analysis to describe heterogeneity within the bone structure. METHODS A high-resolution flat-panel computed tomography scanner (eXplore Locus Ultra) was used to obtain 229,500 images from 221 male and 120 female (total 341) European human skulls. Automated image analysis software was developed to evaluate the fractal dimension D, using the mass radius method. The frontal and the occipital portions of the skull caps of adult females and males were investigated separately. The age dependence of the fractal dimension D was studied by correlation analysis, and the prediction accuracy of age-at-death (aad) estimates for individual observations was calculated. RESULTS D values for human skull caps scatter strongly as a function of age. We found sex-dependent correlation coefficients (CC) between D and age for adults (females CC=-0.67; males CC=-0.05). Prediction errors for aad estimates for individual observations were in the range of ±18 years at a 75% confidence interval. CONCLUSIONS The detailed quantitative description of age-dependent irregularities in the bone microarchitecture of skull vaults through fractal dimension analysis does not, as we had hoped, enable a new aging method. Severe scattering of the data leads to an estimation error that is too great for this method to be of practical relevance in aad estimates. Thus, we disclosed an interesting sex difference.