Π-NET · Pulmonary Imaging Network

Periodic Report Summary - ?-NET (Pulmonary Imaging Network)

Research and scientific activities of the network researchers The ?-NET (see http://www.pi-network.eu for details) develops and explores the potential of new MRI-based tools for the early-diagnosis of lung disease and its therapeutic follow-up, both for clinical treatment and drug development. The network is formed by 10 groups (Ciberes, University of Bordeaux, University of Sheffield, University of Heidelberg, University of Wuerzburg, University CEU San Pablo, AstraZeneca, GE Healthcare, Boehringer Inghelheim and University of Mainz), located in 5 countries (Spain, France, UK, Germany and Sweden) and has successfully recruited 12 researchers (10 early stage researchers and 2 experienced researchers: 6 physicists, 3 chemists, 1 biomedical engineer, 1 mathematician, and 1 medical doctor). The groups hold high quality researchers with previous experience in the network's field of endeavor and high scientific production rate. The expertise within the network covers MRI physics and engineering, as well as the therapeutical, clinical, physiopathological and molecular aspects of respiratory diseases. The network promotes the sharing of expertise and resources among academic and industrial partners, to foster more integrated and holistic solutions to the complex problems around lung disease, which go well beyond what each individual partner could achieve alone. The training and research activities organised in the network have strengthened the excellent existing scientific collabourations of different participant groups and make feasible unforeseen transfer of knowledge, which has opened new aspects for exciting collabourations. ?-NET is addressing training and research issues with relevance to both clinical and preclinical fields by stimulating close transnational interaction across the field of MRI physics, radiology, pulmonology, drug therapy development and molecular imaging. The network has organised so far three out of the four proposed hands-on training workshops with dynamic flow of information among the different trainees, who could get involved in relevant and essential aspects of their future research. The first two workshops were organised in the first year of the network on 'Translational research in lung biology' and 'Workshop on pulmonary imaging techniques', as introduction to lung pathophysiology and to the alternative pulmonary imaging techniques, respectively. The third workshop was organised as complementary training in MRI of the lung. All the training activities were open externally and have presence of internally acknowledged lecturers and participant from different sectors and countries. Finally, the quest for translation to clinical practice of scientific results and engineering developments is one of our main driving forces, since we believe effective improvements in healthcare to be one of the best ways of dissemination of scientific results, because of the impact it has on the life of a big number of people. Thus, as proposed, ?-NET is organising the last workshop on 'Translational aspects of Cardiovascular and pulmonary imaging' in March 2013 (see http://www.tacpi2013.com online) to provide an extensive overview of translational research in thoracic imaging and challenges in drug discovery and development. The network has also conducted extra training activities with the additional aim to promote the new possibilities of interaction among groups and provided a web-based training in complementary and transferable skills. Thus, we have organised two webinars, the first one to show our researchers how to contribute to the contents of the webpage after a major overhaul in the webpage resulting in greatly enhanced functionality. Our webpage is very much visited (with an average entrance of), and it is regularly updated with new records (dissemination, news, events) by all members of the network. The second webinar was programmed as introductory course on the intellectual property rights and legislation valid to protect their new results. The researchers contracted by the network could hence know more details of the IPRs and the patent system. We provided them a generic framework to protect and exploit their scientific results. All these activities were video recorded and are available online to members of the network. As proposed, this webinar service based on Adobe Connect has facilitated the interaction among different researchers who are preparing next courses as base. As part of their training to get complementary translational skills, our young researchers will also organise the research and organisation aspects of the third annual meeting. Thus, they will improve their presentation skills, time management, project management and career development. The network is aiming towards the convergence of scientific and technical innovation in lung imaging with new applications, through shared rigorous methodologies, common study groups, research activities and a quest for excellence in our work practices. The network is working to further enhance the position of each of the partners in the European and worldwide vanguard of lung imaging and metabolomics. The research work was divided in five work packages with the common aim of finding new imaging and spectroscopic-based therapeutic and diagnostic tools, in relation to different pulmonary diseases (such as COPD, cystic fibrosis, asthma, etc.) that will allow the follow-up and consequently timely treatment and increased expectancy and quality of life. As contemplated in the initial plan, these activities include a preclinical work with animal model studies of these diseases and new therapeutic and molecular imaging approaches to understand lung pathophysiology (WP1 and WP5) and clinical work (WP2 and WP3). Within the WP1, MRI experiments with hyperpolarised gases were performed to define imaging makers of the disease, three groups mainly (Ciberes, AZ and BI) have tried to define the experimental conditions for new diagnostic tools using gases for studying inflammatory pulmonary diseases and therapeutic monitoring. We have defined the influence of gas mixture on ADC and published it in the NMR in Biomedicine journal. For proton MRI in animal models of pulmonary inflammation, the group in Bordeaux and the group in AZ have been working together on ultra short echo time sequences (UTE). This work has been selected as oral communication and finally selected as Magna Cum Laude Merit Award at the ISMRM 2012. We have also implemented and applied proton MRI techniques dedicated to the diagnostic of lung diseases and to the monitoring of drug effects in animal models of said diseases using a novel sequence and contrast agent for lighting up the lungs. A publication in magnetic resonance in medicine is also in press. The development and application of new MRI imaging sequences and protocols, combined with the use of contrast agents (see WP5), constitutes the central part of the ESR working in Bordeaux. The WP2 reflects the activities of the group of Heidelberg, the group of Wuerzburg and the group of Sheffield. Computing or post processing methods are developed for 1H pulmonary MR images, with the goal of providing quantitative measurements of lung functionality. The most representative results in Heidelberg included: i) motion correction (image registration) algorithm for pulmonary MRI developed for both 2D and 3D; ii) Fourier decomposition (FD) method for 3D images; iii) quantitative method for measuring lung ventilation for both 2D and 3D pulmonary MRI and iv) a successful test of ventilation method on one initial patient with pleural tumour. The group in Heidelberg wants to evaluate the capabilities of variable flip angle sequences for proton FD pulmonary imaging in a clinical 1.5T MR scanner (Magnetom Avanto, Siemens Healthcare, Germany) and developed untriggered time resolved 2D-bSSFP sequence was used. The group at Wuerzburg is working in different pulse sequence programing for proton lung MRI. One ESR is working in phase contrast MRI in the human lung and for that a short TE gradient echo technique exploiting the MR-phase of the MR-signal was developed and used this quantitative phase mapping technique under different breathing conditions in healthy volunteers. This ESR is also programming a diffusion-weighted (DW) sequence for lung MRI based and first results were presented at the second annual meeting. The second ESR from the University of Wuerzburg is working in the implementation of magnetisation transfer contrast MRI in the human lung. These techniques were installed for 1.5 T and 3 T and are currently tested in healthy volunteers and soon also in patients with lung cancer. The group in Sheffield is also measuring lung function with 1H MRI. This group is interested in obtaining regional measures of pulmonary perfusion, particularly in a subset of patients where administering contrast agent is ill advised. An arterial spin labelled sequences that enable us to measure the flow of tagged spins, a measure that is similar to perfusion. The results will be compared in an adult population with gadolinium enhanced perfusion. The WP3 is mainly devoted to application of hyperpolarised gases to measure lung function. This work reflects mainly the activities of the group of Sheffield although have shown an excellent collabourative work with the group in Heidelberg for segmentation and registration as methods of post processing to compare methods to quantify ventilation. Both groups have acquired images from healthy volunteers and exchanged knowledge around these methods. A different work is with hyperpolarised 129Xe.The group of Sheffield has obtained maps of regional quantified ventilation in humans using Hyperpolarised Helium-3 images acquired in healthy volunteers on a 1.5 T clinical MRI. The study has been completed with a gravitational dependence of ventilation and was presented and got a Magna Cum Laude Award during the ISMRM meeting in Melbourne 2012. The group at Sheffield is interested in measuring red blood cell oxygenation using 129Xe as tracer. They have shown that the resonance frequency of 129Xe dissolved in red blood cells has a linear dependence with RBC oxygenation. Sheffield has further demonstrated that this effect is seen in vivo with a breath hold apnea model of deoxygenation. The WP5 reflects the collabourative work of members of CIBERES, Bordeaux and CEU-San Pablo. With the main objective of delivering new translational health approach to the field of pulmonary imaging, we are introducing new approaches suing new contrast agents and introducing metabolomic studies. As indicated in WP1 we will be able to see the potential of UTE for lung MRI for experiments with new contrast agents. Thus gadolinium-based multimodal nanoprobes developed by the Labouratoire de Physico-Chimie des Materiaux Luminescents are in some cases needed for signal enhancement and increase signal to noise ratio in the lung. The study has allowed detecting the elimination pathway of the administrated nanoparticles and to measure with high precision the great signal enhancement achievable in the lung parenchyma (> 260 %). The work was presented at the last meeting of the ISMRM 2012 and got a Magna Cum Laude Award. Additionally, two articles have been submitted (one to Magnetic Resonance in Medicine and the second to Investigative Radiology). Ciberes is working in the synthesis of new up-converting nanophosphors (UCNPs) micelles for in vivo lung optical imaging. Some of these results were accepted for oral presentation some of these results in the World Molecular Imaging 2012. For metabolomics, in collabouration with clinical actors participating in the network we have searched for a metabolomics fingerprinting of pulmonary diseases to study chronic obstructive pulmonary disease (COPD) and sleep apnea and hypopnea syndrome (SAHS) in human samples, and acute lung injury and ventilation induced lung injury (VILI) using small animal model samples. An abstract to the American Thoracic Society and some publications have been obtained. Several articles have already appeared at the European Respiratory Journal, and a collabourative article has been submitted to the American Journal of Respiratory and Critical Care Medicine. The ultimate goal of this genuinely translational research will be to design ready to use protocols for multiplex analysis of biomarkers useful for early diagnosis and therapeutic monitoring in patients and for pre-clinical purposes. All this work is summarised in WP4 and will result in a workshop (see above) and a common article. The network is fully devoted to disseminate our work worlwide. In this task we count with the inestimable input of all senior investigators and positively with the continuously increasing role of young researchers, which are also giving invited keynote lectures in different fields. We have participated and divulgated our research in very different forums not only imaging related but lung (ESR and ATS annual Meeting), molecular imaging, metabolomics, etc. Examples of invited lectures clearly reflect the current situation of the network in this aspect. 'Lung proton MRI in small animals: where are we and where are we going' at the International functional pulmonary imaging workshop in Philadelphia by Dr Cremillieux, a lecture of 'Proton MRI techniques for functional lung imaging' by Peter Jakob in Australia, an Horizon lecture by Dr Ruiz-Cabello of 'Pulmonary Hypertension and what imaging can provide in the future' in and Madrid-Massachusetts Institute of Technology forum. The network is also providing new insights in the field of pulmonary imaging and the best representation of this is the different talks given by Dr Jim Wild and corresponding divulgation papers in prestigious journals as Insights Imaging 2012

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