| 4. In which ways is the initiative creative and innovative?
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The initiative is innovative as it is the first and unique experiment trying to translate research and clinical practice in a remote service and on-demand. Thanks to the specificity of the initiative it combines resources and efforts from both public and private institutions. Above all, it addresses challenges for which no consolidated strategy exists yet and proposes novel solutions which gained acknowledgement from scientific community with publication in international journals and were awarded in international competitions among the best performing methods. In particular, our methodologies were awarded by the MICCAI Machine Learning Challenge 2014 (https://www.nmr.mgh.harvard.edu/lab/laboratory-computational-imaging-biomarkers/miccai-2014-machine-learning-challenge), MICCAI CADDEmentia Challenge 2014 (https://caddementia.grand-challenge.org), Alzheimr’s disease Big Data DREAM Challenge #1 2015 (https://www.synapse.org/#!Challenges:DREAM) and MICCAI Mild Traumatic Brain Injury Outcome Prediction (https://tbichallenge.wordpress.com). For these competitions, we developed novel solutions for predicting Alzheimer’s disease basing on structural MRI analysis; we implemented complex network analyses to unveil relationships between genes and phenotypes in Schizophrenia; we studied dedicated models to understand how brain injuries can yield a cognitive impairment. All the proposed solutions exploit general methodologies which can in principle be adopted for other diseases, in fact our current activities deal with Multiple Sclerosis and Parkinson's disease.
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| 5. Who implemented the initiative and what is the size of the population affected by this initiative?
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Our initiative is mainly administered through the action of the Italian ministry of Public Instruction and Research. In particular, this was born as an academic effort to lead cross-disciplinary research in a region, Apulia, which was recognized by the European Union to be one of the Italian regions which most lagged behind in terms of development. Accordingly, Apulia became one of the so-called “Convergence regions”. Our mission was to support this effort, mainly economic, driving into the academic environment of the Physics Department of Bari University a genuine spirit of both scientific and technologic innovation aiming at combining our skills and expertise with the personalized medicine field. In collaboration with the local section of the Italian Institute of Nuclear Physics we established a network of relationships and knowledge with public and private hospitals of our regions. We collaborate with: “Policlinico di Bari - Ospedale Giovanni XXIII” public hospital (https://www.sanita.puglia.it/web/ospedalegiovannixxiii/), “Azienda Ospedaliera Card. G. Panico” private hospital (http://www.piafondazionepanico.it) and “Istituto Tumori Bari - Giovanni Paolo II”, an institution dedicated to both research and healthcare. Our services can now reach the whole Apulian population (about 4 million people) and potentially, through the Italian public healthcare system, the whole Italian population (about 60 million people). Moreover, our services are freely available and accessible to every private or public institution. There is also a portal in which whoever makes a request can register and access on the demand some of the services we offer (http://medphysics.ba.infn.it).
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| 6. How was the strategy implemented and what resources were mobilized?
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Over twenty years, Bari team has maturated a long lasting experience in developing algorithms and methodologies in medical physics. The feasible solutions Bari built up made the group generate new and important collaborations with partners from hospitals. Medical applications required by our clinical partners are usually extremely demanding both in terms of scientific background and computational resources, particularly those requiring the analysis of genetic data and imaging. Thus, a particular attention has been paid to ICT, in parallel with the development of sophisticated analysis tools. In particular, Cloud technology appears to fit the requirements of such applications. For example, those technologies are able to provide easily and seamlessly the needed computational power as well as the storage resources to record the data produced. The technological side of our initiative was funded since 2013 to dedicate computational resources to medical applications. The ReCaS-Bari computing farm was built by the ReCaS project (http://www.pon-recas.it), PRISMA project (http://www.ponsmartcities-prisma.it), funded by the Italian Research Ministry of Education, University and Research to the University of Bari and INFN (National Institute for Nuclear Physics) with about 20 million euros. In particular, the data center offers over 180 servers for a total amount of 12000 cores. Each new server hosts 256GB RAM, 4GB RAM per core. Additionally, it offers about 3.5PB of disk space and 2.5PB of tape space.
The data center is one of the biggest Italian supercomputers built with public funds. It's very well integrated into national and international infrastructures like WLCG (World LHC Computing Grid), EGI (European Grid Infrastructure), EGI Federated Cloud. The ReCaS Farm supports several life science communities and projects (Medical Physics, Elixir project, LifeWatch), etc. In particular the life-science community uses up 6% of the farm resources.
The centre offers:
· the possibility to require specific services on virtual machines;
· the possibility to execute parallel jobs based on MPI library;
· facilities to manage the execution of a bunches of independent jobs (automatic grid scheduling) also by means of WebServices;
· “Cloud Storage” services based on WebDav and ownCloud;
The Bari ReCaS data center hosts a cloud infrastructure that is an open source software platform providing a federated IaaS/PaaS cloud computing solution. This cloud environment exploits the hardware infrastructure of Recas-Bari datacenter and respects all the paradigms at the base of the definition of cloud computing: on-demand self-service resources that are pooled, can be accessed via a network, and can be elastically adjusted by the user. We actually are experimenting novel technical solutions to connect all the institutional partners (hospitals) by optic fibers internet connections, by which magnetic resonance images could be rapidly sent to the data center, elaborated by the algorithms and give a response in real time.
We are able now to offer dedicated solutions for personalized medicine within an open source cloud infrastructure.
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| 7. Who were the stakeholders involved in the design of the initiative and in its implementation?
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The initiative was designed by the Bari Medical Physics Group, a cross-disciplinary research group led by prof. Roberto Bellotti, associate professor in Applied Physics at the Bari University. The research group has a consolidate collaboration with the local branch of the National Institute of Nuclear Physics, in particular it is involved with the neuroimaging experiments led by dr. Sabina Tangaro. The research group is involved on activities related to the analysis and understanding of images and patterns, in pattern recognition, machine learning, complex network analysis and related applications to diagnostic medical imaging. The aim of the research group is to develop and deploy related applications in the field of diagnostic medical imaging. Besides, a particular attention is given to the "Big Data" approach, distributed computing on grid environments as the European Grid Infrastructure (EGI) and cloud services for large scale. The research group expertise includes (but is not limited to):
- Computer Aided Detection (CAD) systems for the analysis of biomedical images, in particular brain and mammographic images.
- Pattern Analysis of morphological and genetic alterations due to brain disease.
The scientific productivity of the group is available online at the group site: http://medphysics.ba.infn.it/index.php/publication.
A not secondary role was played within this initiative by the collaboration instituted by the group with private and public hospitals or research institutions. For example, we mention: “Policinico di Bari - Ospedale Giovanni XXIII” public hospital (https://www.sanita.puglia.it/web/ospedalegiovannixxiii/), “Azienda Ospedaliera Card. G. Panico” private hospital (http://www.piafondazionepanico.it) and “Istituto Tumori Bari - Giovanni Paolo II” an institution dedicated to both research and healthcare.
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| 8. What were the most successful outputs and why was the initiative effective?
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Our initiative supports the early diagnosis of cognitive impairment and in general the possible occurrence of brain diseases. The first result we are proud to mention is that the methodologies developed by our group now support the diagnosis of several neurodegenerative diseases, such as Alzheimer’s disease, for which, at the present, no cure exists. This is probably the first and most important output of this initiative. A genuine combination of both personalized medicine and innovation, within the spirit of UN SDGs.
In 2010, the number of people over 60 years of age living with dementia was estimated at 35.6 million worldwide. This number is expected to almost double every twenty years. Early and accurate diagnosis has great potential to reduce the social and economic costs related to care and living arrangements as it gives patients access to supportive therapies that can help them maintain their independence for longer and delay institutionalization, achieving a better quality of life. Thus, a second output of this initiative is the development of personalized medicine strategies for early diagnosis, a benefit which could greatly increase the economic sustainability of healthcare.
The methodologies developed by our group allow robust morphological analyses of the human brain on demand, thus our technical background and the computational resources we have are made available to other scientific or clinical communities which can take benefit from our services. We think that sharing our knowledge with other communities and offering for free services of analysis and support to diagnosis is one of the most important achievements we obtained. A third output of our initiative is the sharing of knowledge and the birth in Apulia of a truly cross-disciplinary research environment.
A fourth output is the boost in innovation, let us think to ReCaS, that our initiative has carried in a territory, such as Apulian region, which stays behind in terms of development.
A fifth output is the virtuous circle our initiative has generated. Let us think to the ongoing collaborations with healthcare institutions and, more importantly, the improvements that are ongoing, as the new project with the “Azienda Ospedaliera Card. G. Panico” private hospital, according to the hospital and ReCaS will be connected via ultra fast fiber optics so physicians could rapidly store and access to all their medical data, require automated analysis and get results in real time.
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| 9. What were the main obstacles encountered and how were they overcome?
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The difficulties we encountered were twofold. Firstly, a particular mention deserves the search for funds, the management, the public relationships, the political and marketing efforts performed. The design of the initiative lasted for a decade, culminating in the awarding of about 40 million euros from the European Community for the construction of the ReCaS data center and the implementation of the PRISMA cloud platform. This work was really hard for a public research group, whose main activities used to be the study of high energy physics or the Higgs boson. In fact, we had to win friction forces even inside our community to explain this initiative and convince the community of its goodness.
Secondly, this initiative would not be a success without the work of many young researchers and their team leaders driving the every-day research activity. The methodologies we have developed required thousands of hours of work from more than 20 people from the Bari University and the National Institute of Nuclear Physics. It was of fundamental importance, as facing scientific challenges still open, the development of innovative strategies, but at the same time, it was important to keep these solutions friendly for the use of communities, let us think about clinicians, whose scientific background is far from those of physicists or computer scientists.
Finally, we had to develop customized technological solutions according to the specifications of the end-users. Even in this case a remarkable effort was made to overcome existing technical limitations.
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