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The eTUMOUR consortium has developed from multi-disciplinary collaborations between several of its partners that have extended over a number of years (resulting in several joint publications).
These were funded by the European Union in the form of Concerted Actions under Biomed 1 and 2, and by other bodies including the British Council and the Royal Society. Likewise, an important number of the present partners have participated in the EC FP5 INTERPRET project (IST-1999-10310): International Network For Pattern Recognition of Tumours Using Magnetic Resonance. A large number of European clinical and scientific expertise groups in MRS of brain tumours are cooperating as partners in this eTUMOUR project. Among the 21 partners of eTUMOUR, there are 14 hospitals (five of them as subcontractors of P2, and 5 included in P1), 7 research institutions (mainly Universities) and finally 7 companies, among them 3 of the largest NMR equipment producers, and 4 SME. Seven countries of EC are participating in the eTUMOUR, 1 European country not EC is also involved in the project, Poland (P21). Finally it is also interesting to point out the collaboration of two South American countries, Argentina as Partner (P20) and Chile (Hospital del Trabajador and Medicine Faculty of Concepci?n) cooperating directly with P1, which can yield information from a different etiologic group of patients.
Universitat de Valencia (Estudi General, UVEG). Partner 1. In this partner a strong multi-disciplinary collaboration has been developed during the last four years among research and clinical groups from: radiology, neurology, neurosurgery, physical chemistry, biochemistry and genetics. This partner is constituted by: a) different departments of the UVEG: Physical Chemistry, Biochemistry and Central Service of Experimental Research (SCIE); and b) four hospitals: Cl?nica Quir?n, Hospital Universitario Dr. Peset, Hospital La Ribera-Alzira and Hospital Universitario La Fe. Likewise, during the last four years an important cooperation has been also developed with the bioinformatic group of Universidad Polit?cnica de Valencia (UPV) (Partner 15) to design, implement and produce software for processing and displaying single and multivoxel MRS spectra and to develop classifiers for neurodegenerative pathologies. All these groups will continue working together and will be co-ordinated by Prof. Bernardo Celda (UVEG), who will play the role of Co-ordinator of the Consortium. The P1 will (i) provide retrospective data for developing a web accessible database, (ii) accrue patient MR imaging and spectra and clinical data and participate in QC and data validation procedures, (iii) acquire ex vivo HR MAS (metabolomic) data from biopsies, (iv) acquire ex vivo DNA microarray (transcriptomic) data from biopsies, (v) develop pre-processing programs for MRS raw data spectra, (vi) provide user feedback on prototype graphical user interfaces, (v) provide biochemical, metabolic and genetic data interpretation to assist pattern recognition developments. UVEG will also collaborate in the management of WP2 in the HR MAS consensus protocol specification, acquisition and analysis. The Scientific Manager (SM) of the project will be based at this centre.
Universitat Aut?noma de Barcelona and Associated Hospitals (subcontractors IDI, Centre Diagn?stic Pedralbe, Hospital Clinic-Universitari de Barcelona and Hospital de Sant Pau from Barcelona and M?tua de Terrassa). Partner P2. These centers work closely together and will be co-ordinated by Prof. Carles. Ar?s (UAB), who will also play the role of coordinator of WP2. They will (i) assemble the preliminary dataset (manage WP2), (ii) accrue patient spectra and clinical data and participate in QC and data validation procedures, (iii) acquire ex vivo HR MAS (metabolomic) data from biopsies, (iv) acquire ex vivo DNA microarray (transcriptomic) data from biopsies, (v) participate in the development of a suite of programs to transform raw spectra, (vi) provide user feedback on prototype graphical user interfaces, (vii) provide biochemical, metabolic and genetic data interpretation to assist pattern recognition developments. This centre was co-ordinator of the EC FP5 project (IST-1999-10310) INTERPRET.
St George?s Hospital Medical School and Associated Hospitals. Partner P3. This centre will participate in (i) provide retrospective data for developing a web-accessible database (ii) accrue patient spectra and clinical data and participate in QC and data validation procedures, (iii) acquire ex vivo HR MAS (metabolomic) data from biopsies, (iv) acquire ex vivo DNA microarray (transcriptomic) data from biopsies, (v) evaluate pattern recognition, (vi) develop methods to minimise incompatibilities between different MRS acquisition protocols, (vii) provide user feedback on prototype graphical user interfaces, (viii) provide biochemical, metabolic and genetic data interpretation to assist pattern recognition developments. SGHMS played a crucial role as partner and responsible of some WP in EC FP5 project (IST-1999-10310) INTERPRET
Department of Radiology, Stichting Katholieke Universiteit Nijmegen. Partner P4. This centre, which has experience of managing multi-centre trials of MRS, as in EC FP5 project (IST-1999-10310) INTERPRET, will (i) develop and cooperate in the management of the procedures for standard spectrum acquisition and quality control (WP2), specifically Dr. Arend Heerschap will be the responsible of the committee quality data control CQDC, (ii) acquire patient spectra.
Department of Analytical Chemistry, Catholic University of Nijmegen. Partner P5. This partner is one of the leading chemometrics groups in Europe and is very experienced in the development of pattern recognition systems (some for previous EU framework programmes, as in EC FP5 project (IST-1999-10310) INTERPRET). Its role in the consortium is to develop methods for pre-processing and classifying multivoxel spectra and to actively participate and collaborate in WP3 (Prototype Classifiers, through Pattern Recognition technique).
INSERM U594, Grenoble. Partner P6. This centre has developed the Nosologic Imaging Method that will form an important part of the project. It will (i) accrue patient data in multi-voxel form, suitable for nosologic imaging, clinical data, and participate in QC and data validation procedures, (ii) acquire ex vivo HR MAS (metabolomic) data from biopsies (iii) develop pattern recognition and display software methods for nosologic images, (iv) provide user feedback on prototype graphical user interfaces, (v) help in DSS development, (vi) provide biochemical, and metabolic interpretation to assist pattern recognition developments. This partner will coordinate the WP4, DSS development, in close technical collaboration with Scito.
Microart. Partner P7, is a SME featuring an extensive expertise in Pattern Recognition and DSS development and dissemination. They will (i) apply the methodology of ?Agent Architecture? for a secure database development keeping patients privacy (WP2),(ii) help in the development of an industrial prototype for the DSS (WP4), (iii) help and coordinate the diffusion and implementation WP7.
Hospital San Joan de Deu. Partner P8, is a centre highly specialized in pediatrics and with a highly qualified imaging diagnostic service. The responsible for the eTUMOUR project in this centr, Dr. Antoni Capdevila, has experience in MRS trials by its participation on the INTERPRET project (EC FP5 project IST-1999-10310). This center will (i) develop and cooperate in the management of the procedures for standard spectra acquisition and quality control (WP2), in particular for children, (ii) acquire children spectra. This partner will be in direct collaboration with P2.
Pharma Quality Europe, Partner P9, is a SME featuring an extensive expertise quality control in clinical and medical systems. They will (i) help in the quality control system either for clinical, MRI/MRS, HR MAS and DNA microarray data or web accessible database, (ii) coordinate the whole quality assessment of the project and of DSS prototype (WP6), (iii) collaborate in the clinical demonstration of added value (WP5).
Hyperphar, Partner P 10, is a SME featuring an extensive expertise quality control in clinical and medical trials. The clinical demonstration of added value is a crucial WP in eTUMOUR (WP5), because it will allow the direct and real test of the DSS prototype in clinical routine. They will (i) help in the specification and setting up of the clinical demonstration of added value, (ii) coordinate, control and do the whole clinical demonstration of added value (WP5), (iii) collaborate in the quality assessment (WP6).
Katholieke Universiteit Leuven, ESAT-SCD (KUL), Partner P 11. This partner provides leading expertise in mathematical engineering, biomedical signal processing and bioinformatics in Europe and is very experienced in the development of pattern recognition systems (some for previous EU framework programmes, as a subcontractor in EC FP5 project (IST-1999-10310) INTERPRET). Its role in the consortium is to develop methods for pre-processing and classifying multivoxel spectra (Prototype Classifiers, through Pattern Recognition technique).
Philips Medical Systems, Partner P12, has supported in-vivo MR Spectroscopy during its development with product solutions and works-in-progress packages for research groups for many years. They will (i) help defining the needs for clinical routine, (ii) give input for quality control of the software (WP6), (iii) specify data formats which have to be supported by the software (WP2, WP3 and WP4), (iv) establish contacts with users who perform MR spectroscopy in a clinical setting (WP?s 5 and 7), and (v) plan the use of the software on Philips systems after the development (WP7 and 8).
SIEMENS AG, Medical Solutions. Partner P13, has supported in-vivo MR Spectroscopy during its development with product solutions and works-in-progress packages for research groups for many years. They will (i) help defining the needs for clinical routine, (ii) give input for quality control of the software (WP6), (iii) specify data formats which have to be supported by the software (WP2, WP3 and WP4), (iv) establish contacts with users who perform MR spectroscopy in a clinical setting (WP?s 5 and 7), and (v) plan the use of the software in connection with or directly on Siemens systems after the development (WP7 and 8).
Scito, Partner P14 is a SME featuring a unique expertise in DSS and industrialization and marking. They will (i) help in the development of a scientific and industrial prototype for the DSS and (ii) contribute to establish the marketing/ licensing/ certification strategy of eTUMOUR products in the TIP. Scito will also manage WP8.
UNIVERSIDAD POLIT?CNICA DE VALENCIA, Partner P 15. This partner has extensive expertise in bioinformatics and its biomedical applications and is very experienced in the development of pattern recognition and DSS systems. P15 has also developed processing and analysis software for multivoxel MRS spectra. Its role in the consortium is to develop methods for pre-processing and classifying multivoxel spectra, to manage WP3 (Prototype Classifiers, through Pattern Recognition technique), to cooperate in DSS development (WP4), and actively help in diffusion and implementation of eTUMOUR project in collaboration with P7
DEUTSCHES KREBSFORSCHUNGSZENTRUM (DKFZ), Partner P16. The German Cancer Research Centre is a partner with a large experience in MRS application on cancer diagnosis. They will (i) provide retrospective preliminary data for dataset preparation, (ii) accrue patient spectra and clinical data and participate in QC and data validation procedures, (iii) provide user feedback on prototype graphical user interfaces.
BRUKER BIOSPIN, Partner P17. This partner has participated in the development of high field in-vivo MR Spectroscopy (? 3T) and in High Resolution NMR in solution and solid state. Particularly important are their contributions to High Resolution Magic Angle Spinning (HR MAS) and its application to ?liquid like? systems, as tissues. They will (i) help defining the needs for clinical routine, (ii) give input for quality control of the software (WP6), (iii) specify data formats which have to be supported by the software (WP2, WP3 and WP4), (iv) help in the specification of HR MAS of biopsies, (v) develop new sequences for HR MAS of tissue biopsies, (vi) establish contacts with users who perform MR spectroscopy in a clinical setting (WP?s 5 and 7), and (vii) plan the use of the software on Bruker systems after the development (WP7 and 8).
Institute of Child Health, University of Birmingham and Birmingham Children?s Hospital NHS Trust, Partner P18. This partner has extensive experience in diagnosing and managing child brain tumours with neurosurgery and paediatric neuro-oncology on site. The Paediatric Brain Tumour Research Group has current projects in tumour genetics, in vivo and in vitro MRS and has considerable experience in clinical databases. As part of this research tissue frozen tissue is already routinely collected from patients at operation. Birmingham Children?s Hospital was the site of a recent Engineering and Sciences Research Council workshop on the ?development of functional imaging for the diagnosis, management and understanding of childhood brain tumours?. Dr Peet and Dr Grundy are members of the Brain Functional Imaging Working Group of the United Kingdom Childhood Cancer Research Group which co-ordinates projects involving MRS and in the UK. This partner will provide about 30 newly diagnosed child brain tumours/per year. They will (i) provide retrospective preliminary data for dataset preparation, (ii) accrue patient spectra, in vitro MAS, genetic data and clinical data and participate in QC and data validation procedures, (iii) provide user feedback on prototype graphical user interfaces particularly with reference to paediatric issues.
Institut National de la Sant? et de la Recherche M?dicale, U318, Partner P19. This partner has expertise in DNA microarray applications to the diagnosis of different pathologies and has strong collaboration with P6. They will (i) acquire ex vivo DNA microarray (transcriptomic) data from biopsies, (ii) help in the specification of DNA microarray consensus protocol, (iii) help in pattern recognition development through comparative analysis of genetic and in vivo MRS metabolic data.
Fundaci?n para la Lucha contra Enfermedades Neurol?gicas de la Infancia, Partner P20, has been advisory group member of the INTERPRET project and has expertise in MRS and diffusion applications to brain tumours. They will (i) provide retrospective preliminary data for dataset preparation, (ii) accrue patient spectra and clinical data and participate in QC and data validation procedures, (iii) provide user feedback on prototype graphical user interfaces.
Medical University Lodz, Partner P21, has experience in MRI/MRS diagnosis applications to brain tumours. They will provide retrospective preliminary data for dataset preparation, (ii) accrue patient spectra and clinical data and participate in QC and data validation procedures, (iii) provide user feedback on prototype graphical user interfaces.
Additional clinical partners may be needed after the initial 18 month phase to increase the amount of clinical data gathered and participate in the clinical demonstration of added value phase of the project. This has been taken into account in the budget of partners that will incorporate them as subcontractors.
Justification for inclusion of FLENI (P20) in eTUMOUR. FLENI stands for ?Fundaci?n para la Lucha contra las Enfermedades Neurol?gicas de la Infancia? and is located in Buenos Aires (Argentina). This clinical center is equipped with state-of-the-art human MR scanners and participated actively in the former INTERPRET project, albeit without funding, contributing more than 30 cases to the project database and abiding by all consensus acquisition and quality control protocols. This previous collaboration makes us think that their participation in the present eTUMOUR proposal is of outmost interest in at least three aspects:
1. They can now provide MR, clinical data and biopsy material abiding by all consensus acquisition and QC protocols on about 50 cases per year (including children). This would be a very important contribution to the total number of cases nedeed for proper classifier development within eTUMOUR.
2. They will provide data from non-european patients, which, for a DSS that strives to have a leading role in world use, is always going to be an important asset.
3. They will be very influential in the Diffussion and Implementation part of the project, providing penetration in the South American scanner-equipped centers market.
The role of SME in the Proposed Work: Participating SMEs will contribute with software development, quality assessment and clinical demonstration of added value monitoring according to standards compatible with certification processes. SMEs will benefit from increased exposure to the needs of the biomedical field, and can participate in the maintenance and management of the open source software platform developed.
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