Sönke Bartling

Imaging anti-angiogenic treatment response with DCE-VCT, DCE-MRI and DWI in an animal model of breast cancer bone metastasis

As current classification systems for the assessment of treatment response in bone metastasis do not meet the needs of oncologists, new imaging biomarkers are desirable. Therefore, the diagnostic impact of dynamic contrast enhanced (DCE)-volumetric computed tomography (VCT) (descriptive analysis), DCE-MRI (two-compartment model) and diffusion weighted imaging (DWI) for monitoring anti-angiogenic therapy effects of the VEGF antibody bevacizumab in breast cancer bone metastases in rats was studied. Nude rats (n=8 animals treated with bevacizumab and n=9 untreated control rats) with site-specific osteolytic bone metastasis of the hind leg were imaged with a 1.5T clinical MRI-scanner in an animal coil as well as in a volumetric CT-scanner at days 30, 40, 50 and 60 after inoculation of MDA-MB-231 human breast cancer cells. From these data, osteolytic lesion size (OLS), peak enhancement (PE), area under the curve (AUC), amplitude (A), exchange rate constant (k(ep)) and apparent diffusion coefficient (ADC) were determined in bone metastases. Prior to changes in OLS (p< or =0.05 at days 50 and 60) there was already a significant decrease in PE, AUC and A (p< or =0.05 at days 40-60) in treated animals compared to controls. However, for k(ep) and ADC there were no significant differences between the groups at any time point (p>0.05 at days 40-60). In conclusion, anti-angiogenic treatment response in osteolytic breast cancer bone metastases can be assessed early with surrogate markers of vascularization, while DWI appears to be insensitive.

A mouse model for congenital myasthenic syndrome due to MuSK mutations reveals defects in structure and function of neuromuscular junctions

In the muscle-specific tyrosine kinase receptor gene MUSK, a heteroallelic missense and a null mutation were identified in a patient suffering from a congenital myasthenic syndrome (CMS). We generated one mouse line carrying the homozygous missense mutation V789M in musk (musk(V789M/V789M) mice) and a second hemizygous line, resembling the patient genotype, with the V789M mutation on one allele and an allele lacking the kinase domain (musk(V789M/-) mice). We report here that musk(V789M/V789M) mice present no obvious abnormal phenotype regarding weight, muscle function and viability. In contrast, adult musk(V789M/-) mice suffer from severe muscle weakness, exhibit shrinkage of pelvic and scapular regions and hunchback. Musk(V789M/-) diaphragm develops less force upon direct or nerve-induced stimulation. A profound tetanic fade is observed following nerve-evoked muscle contraction, and fatigue resistance is severely impaired upon a train of tetanic nerve stimulations. Electrophysiological measurements indicate that fatigable muscle weakness is due to impaired neurotransmission as observed in a patient suffering from a CMS. The diaphragm of adult musk(V789M/-) mice exhibits pronounced changes in endplate architecture, distribution and innervation pattern. Thus, the missense mutation V789M in MuSK acts as a hypomorphic mutation and leads to insufficiency in MuSK function in musk(V789M/-) mutants. These mutant mice represent valuable models for elucidating the roles of MuSK for synapse formation, maturation and maintenance as well as for studying the pathophysiology of a CMS due to MuSK mutations.

Virtual endoscopy of the middle ear: experimental and clinical results of a standardised approach using multi-slice helical computed tomography.

Abstract. Virtual endoscopy (VE) enables non-invasive 3D endoluminal imaging of the middle ear by post-processing of CT data. To optimise the clinical application a standardised approach was evaluated in normal and pathologic cases. Data acquisition was performed using multi-slice helical CT in 20 normal patients and 15 patients with malformation or trauma. Virtual endoscopy of the tympanic cavity and 3D images of the ossicles were generated using surface and volume rendering. Qualitative assessment of the representation of anatomical structures was performed in normal patients. In 15 pathological cases the diagnostic benefit was evaluated by comparing the 3D images to the 2D images and intra-operative findings. In all 35 cases 3D imaging was possible using the standardised approach. The ossicular chain as well as the bony and soft tissue structures of the tympanic cavity were visualised in 20 normal patients. In 7 of 8 patients with malformation and 1 of 7 patients with trauma the original diagnosis was changed by 3D imaging. Standardisation and evaluation of the method in normal patients is essential as it enhances the diagnostic reliability. Virtual endoscopy facilitates understanding of the complex anatomy of the middle ear. In cases of suspected malformation and confirmed trauma it is helpful for diagnosis and surgical planning.

Constrained reconstructions for 4D intervention guidance

Image-guided interventions are an increasingly important part of clinical minimally invasive procedures. However, up to now they cannot be performed under 4D (3D + time) guidance due to the exceedingly high x-ray dose. In this work we investigate the applicability of compressed sensing reconstructions for highly undersampled CT datasets combined with the incorporation of prior images in order to yield low dose 4D intervention guidance. We present a new reconstruction scheme prior image dynamic interventional CT (PrIDICT) that accounts for specific image features in intervention guidance and compare it to PICCS and ASD-POCS. The optimal parameters for the dose per projection and the numbers of projections per reconstruction are determined in phantom simulations and measurements. In vivo experiments in six pigs are performed in a cone-beam CT; measured doses are compared to current gold-standard intervention guidance represented by a clinical fluoroscopy system. Phantom studies show maximum image quality for identical overall doses in the range of 14 to 21 projections per reconstruction. In vivo studies reveal that interventional materials can be followed in 4D visualization and that PrIDICT, compared to PICCS and ASD-POCS, shows superior reconstruction results and fewer artifacts in the periphery with dose in the order of biplane fluoroscopy. These results suggest that 4D intervention guidance can be realized with todays flat detector and gantry systems using the herein presented reconstruction scheme.

Image Findings of Patients with H1N1 Virus Pneumonia and Acute Respiratory Failure

RATIONALE AND OBJECTIVES The aim of this study was to assess the findings of chest radiography and high-resolution computed tomography in patients requiring intensive care unit treatment for severe H1N1 virus pneumonia. MATERIALS AND METHODS In 2009, 10 patients required treatment in an intensive care unit for confirmed H1N1 pneumonia. All patients underwent chest radiography and high-resolution computed tomography. All 10 patients required mechanical ventilation because of respiratory failure. Nine patients presented with severe acute respiratory distress syndrome, and one patient died. Four patients underwent extracorporeal membrane oxygenation (ECMO) therapy. The results of chest radiography and high-resolution computed tomographic scans of these patients were systematically analyzed. RESULTS The mean age of all patients was 44.1 +/- 12.3 years. All 10 patients showed abnormal results on chest radiography. The radiographic abnormalities were bilateral and multifocal in 10 patients. The predominant radiographic findings were consolidations (n = 9), ground-glass opacities (n = 8), and reticular opacities (n = 2). The most frequent computed tomographic findings at presentation consisted of bilateral ground-glass opacities (n = 9), pleural effusion (n = 9), areas of consolidation (n = 8), interstitial marking (n = 8), and crazy paving (n = 4). All patients undergoing ECMO therapy showed extensive bilateral ground-glass opacities, multifocal areas of consolidation, and crazy paving. Pleural effusion was present in three of four patients undergoing ECMO therapy. CONCLUSION Patients requiring treatment in an intensive care unit for severe H1N1 pneumonia are at high risk for developing acute respiratory distress syndrome and frequently require ECMO therapy.

Towards Another Scientific Revolution

In this introductory chapter we establish a common understanding of what are and what drives current changes in research and science. The concepts of Science 2.0 and Open Science will be introduced. As such we provide a short introduction to the history of science and knowledge dissemination. We explain the origins of our scientific culture which evolved around publication methods. Interdependencies of current concepts will be elucidated and it will be stated that the transition towards Open Science is a complex cultural change. Reasons as to why the change is slow are discussed and the main obstacles are identified. Next, we explain the recent changes in scientific workflows and how these cause changes in the system as a whole. Furthermore, we provide an overview on the entire book and explain what can be found in each chapter.

Cochlear implantation in children with bacterial meningitic deafness: The influence of the degree of ossification and obliteration on impedance and charge of the implant.

Abstract Objectives To determine impedance values and charge consumption following cochlear implantation post-meningitic deaf children depending on the grade of cochlear ossification and obliteration. Methods Post-meningitic deaf (n = 49) and control (n = 43) children treated with cochlear implants were included in the study. Impedance and charge values were calculated for each group. The degree of ossification of the cochlea was evaluated from a high-resolution computed tomography (HRCT) scan whereas the degree of obliteration was determined intraoperatively by the surgeon. Results Pneumococci were the principal pathogen responsible for bacterial meningitis, followed by meningococci. In HRCT scans, the degree of ossification was 1 and 2 in 29% of patients. The results of the intraoperative assessment of the cochlea showed obliteration grade 1 in 38% and grade 2 in 23% of cases. Children in the meningitis group showed significant higher impedances comparing to the control group. A significantly increased charge consumption was observed in patients with a grade 2 ossification when compared to those without ossification (P = 0.02). Discussion Cochlea implanted children with meningitis-related deafness exhibit higher impedances, especially in the region of the basal and middle turn, however, not depending on the degree of cochlear ossification. High impedances and charge in the meningitis group may be explained by alterations in the central auditory pathway or on the electrode surface. Conclusion To optimize the outcome in post-meningitic deaf children, surgery is advisable at an early stage prior to the onset of cochlear ossification.

Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas

Aims To evaluate the incremental value of low endothelial shear stress (ESS) combined with high-resolution magnetic resonance imaging (MRI)- and computed tomography angiography (CTA)-based imaging for the prediction of inflamed plaque. Methods and results Twelve hereditary hyperlipidaemic rabbits underwent quantitative analysis of plaque in the thoracic aorta with 256-slice CTA and USPIO-enhanced (ultra-small superparamagnetic nanoparticles, P904) 1.5-T MRI at baseline and at 6-month follow-up. Computational fluid dynamics using CTA-based 3D reconstruction of thoracic aortas identified the ESS patterns in the convex and concave curvature subsegments of interest. Subsegments with low baseline ESS exhibited significant increase in wall thickness and plaque inflammation by MRI, in non-calcified plaque burden by CTA, and developed increased plaque size, lipid and inflammatory cell accumulation (high-risk plaque features) at follow-up by histopathology. Multiple regression analysis identified baseline ESS and inflammation by MRI to be independent predictors of plaque progression, while receiver operating curve analysis revealed baseline ESS alone or in combination with inflammation by MRI as the strongest predictor for augmented plaque burden and inflammation (low ESS at baseline: AUC = 0.84, P < 0.001; low ESS and inflammation by molecular MRI at baseline: AUC = 0.89, P < 0.001). Conclusion Low ESS predicts progression of plaque burden and inflammation as assessed by non-invasive USPIO-enhanced MRI. Combined non-invasive assessment of ESS and imaging of inflammation may serve to predict plaque with high-risk features.

Dynamic Publication Formats and Collaborative Authoring

While Online Publishing has replaced most traditional printed journals in less than twenty years, today’s Online Publication Formats are still closely bound to the medium of paper. Collaboration is mostly hidden from the readership, and ‘final’ versions of papers are stored in ‘publisher PDF’ files mimicking print. Meanwhile new media formats originating from the web itself bring us new modes of transparent collaboration, feedback, continued refinement, and reusability of (scholarly) works: Wikis, Blogs and Code Repositories, to name a few. This chapter characterizes the potentials of Dynamic Publication Formats and analyzes necessary prerequisites. Selected tools specific to the aims, stages, and functions of Scholarly Publishing are presented. Furthermore, this chapter points out early examples of usage and further development from the field. In doing so, Dynamic Publication Formats are described as (a) a ‘parallel universe’ based on the commodification of (scholarly) media, and (b) as a much needed complement, slowly recognized and incrementally integrated into more efficient and dynamic workflows of production, improvement, and dissemination of scholarly knowledge in general.

CT-Guided Interventions: Current Practice and Future Directions

Computed tomography (CT) plays an important role in interventional procedures such as biopsy, abscess drainage, tumor ablation, catheter placement, and orthopedic instrumentation. All these procedures involve precise incremental advancement of a needle or a probe. This chapter reviews the current state of the art and advanced applications of CT in interventional procedures, including the use of C-arm CT, multi-detector CT, and ultrahigh-resolution flat-panel CT. Interventional capabilities of C-arm CT, which combines the advantages of a digital flat-panel detector with the versatility of a C-arm, are described. Ultrahigh-resolution flat-panel CT, another technology-based flat-panel detector, is also described. Recent development of portable CT not only provides on-site imaging for critically ill patients; it also enables faster response to imaging requests and increased productivity of the care team. The new advancements covered by this chapter introduce robot-assisted image-guided interventions. The current CT-guided intervention only provides 3D data in a discontinuous, manipulate, and rescan fashion. A new paradigm for real-time 4D imaging, which could play an important role in intervention guidance in the near future, is described and illustrated with the help of examples.