Ebook: Advances in Biomedical Engineering

This volume contains the final reports of twenty-one of the projects supported by the Commission of the European Communities within the framework of the Medical and Health Research Programme (1987-1991) - MHR4 - in the area of biomedical engineering.

Despite the social and economic importance of biomedical and health research, it is only fairly recently that the European Community became involved in research and technological development in this research sector. It was not until 1978 that the Commission of the European Communities was authorized to promote coordination of research projects in the various countries in very limited and strictly defined areas of common interest. Since this “pilot” work proved successful and considerably improved the effectiveness of efforts made at national level in the fields chosen, the EC Member States showed both interest and confidence in this then new form of EC action. As a result, in 1982, the Council of the Ministers of the Member States finally adopted a wider-ranging and more coherent research coordination programme in biomedicine and health. Since then, this programme has grown substantially both in size and content.

The general goal of the programme is clearly to contribute to a better quality of life by improving health, and its distinctive feature is to strengthen European collaboration in order to achieve this goal.

The 4th EC Medical and Health Research Programme (MHR4) consisted of six research targets. Four were related to major health problems: cancer, AIDS, age-related problems, environmental and life-style related problems; two were related to health resources: medical technology (i.e. biomedical engineering) and health services research.

Biomedical engineering has formed an integral part of the EC biomedical and health research programmes since their quite modest beginnings in 1978, when only three collaborative research projects - “concerted actions” - were supported by the EC; as a matter of fact one of those early projects dealt with extra-corporeal oxygenation. Collaboration is not natural and spontaneous within the scientific community which rather believes in competition to ensure scientific progress. In the early period of the EC programme, biomedical engineering may be said to have served as the driving force in the process of fostering some collaboration spirit in the European biomedical research community. It was so successful that in 1987, biomedical engineering consumed nearly 45% of the total programme's budget with sixteen projects running!

The ultimate goal of the biomedical engineering part of the programme has been to contribute to the improvement of the quality of health care, as well as to the containment of its costs. Health technology assessment has gained further importance in view of the completion of the internal market within the EC. Such assessment may provide essential information for decision making at all levels, (i.e. political, health services, medical). Because of the extremely rapid development of technology, results of assessment studies should become available quickly. Besides evaluation of biomedical devices is expensive in financial and manpower terms, mainly because of the qualified personnel it involves and the need to recruit patients. Inappropriate use, or wrong application of technology, adds to the increase in health costs, not so much technology in itself. These are the major reasons justifying performing such evaluation at European level, as this makes it possible to obtain more reliable data more quickly, because of large sizes of samples. Accordingly, health technology assessment, in particular assessment of technical and clinical efficacy, has come under biomedical engineering in the EC medical research programmes.

Multi- and inter-disciplinarity has always characterized the projects supported in the biomedical engineering part of the EC programme, and such an approach still remains strongly encouraged. In biomedical engineering, the necessity for a closer collaboration between engineers and clinicians has always been felt, and this has been encouraged by making it an essential condition before recommending a research proposal for support.

A study performed a few years ago by Centre de Sociologie de l'Innovation (Ecole des Mines, Paris) (*) was the first attempt at defining the characteristics of the EC medical research programmes. It confirmed that, although the level of EC funding remains modest (**), these programmes stand among the major EC research programmes when using the number of involved teams as an indicator, and the only one which has adopted an original approach to financial support, namely the concerted action, as its principal mode of implementation. In 1990, the 117 ongoing actions within MHR4 involved 3,500 teams altogether, that is an average of 30 teams in each action all over Europe (i.e. the twelve EC Member States plus Austria, Norway, Finland, Sweden, Switzerland, Turkey).

Concerted actions remain the principal mode of implementation, together with centralized facilities and fellowships. Funds are provided by the EC for activities which consist of research collaboration and co-ordination in EC Member States and in other European participant countries. Networks of research institutes can be set up and supported by means of meetings, workshops, short-term staff exchanges and visits to other countries; preparation and distribution of materials and reference products, that is, for quality control; centralised data handling, storage and statistical analysis. The concerted action budget also covers the dissemination of information as early, as fully and as frequently as possible. The funds are not primarily intended as direct research grants; the institutes must fund the research activities carried out within their own countries - it is the international coordination activities which are eligible for Community support. Each research network is placed under the responsibility of a project leader; he/ she is generally assisted by a project management group representing the teams participating in the network.

The Project Leader, that is the author of each of the following chapters included in this volume, is the cornerstone of the concerted action system, as he is accountable vis-à-vis the Commission and is the only recipient of EC funds. “He is fully responsible for the operational definition of the project from mobilizing teams to disseminating results, for organizing the work and arranging the logistics of staff exchanges, often considered to be the strategic hub of concerted actions.” (*)

But successful projects are based on the favourable collaborative atmosphere which has developed among the participants themselves, without whom, in the end, nothing could be achieved. Accordingly, the Project Leaders indicated here as authors should be considered rather as spokesmen for the participants involved in the projects.

In addition, within the concerted action system, the role of COMAC-BME should not be underestimated; COMAC-BME was the advisory committee for biomedical engineering until the end of MHR4. It consisted of usually two experts in the field of biomedical engineering for each participating country. The list of COMAC-BME members is provided in the annexes. Together with the project leaders and participants, COMAC-BME members substantially contributed to the definition of this original approach to public support for research, that is the concerted action. During the course of MHR4, COMAC-BME has witnessed a major change in its role. Before 1989, its tasks were in fact to contribute to the initiation and preparation of proposals, as well as to supervise and monitor the progress within ongoing projects. At that time, it was thought that this process of going through a nurturing phase for potential new projects was an essential ingredient for success, although it took time; mainly, collaborative spirit could develop during that phase. Since 1989, calls for proposals were introduced, and COMAC-BME, together with the other advisory committees for MHR4, was changed into more of a usual selection committee, while keeping its role as a supervising and monitoring advisory committee. Since then, the calls for proposals have been extremely popular, showing the very high level of demand among the European biomedical research community. As underlined in the previously-mentioned study (*), “the key to the success of concerted actions lies in the capacity to rally teams (at least an active core) behind the same objective”. In such an endeavour, investment in human resources is the decisive factor. This was understood by COMAC-BME which tried to implement among themselves what it was preaching to others, that is the collaborative spirit, especially among engineers and clinicians coming from a variety of backgrounds.

Because of the original features of the concerted action mechanism, it is not easy to evaluate the outcome with usual criteria and indicators, but this should not lead to underestimate the achievements.

In spite of modest financial incentives imposing little obligation, in the previously-mentioned survey (*), the participants, on average, declared quite a high degree of involvement in the concerted action activities. Nearly all concerted actions brought together researchers and clinicians, who are in fact the potential users. Such “interweaving” of research and clinical practice enabled operational results to be directly integrated into practice in harmonized ways throughout Europe; this may be considered similar to “industrial” developments found in other contexts. At the same time, new research structures, that is research networks, have been established; they are both irreversible and flexible, because they are based on human relations, and imply a certain degree of harmonization among experimental practices.

The EC biomedical research programmes have undeniably reached a key stage in their evolution, mainly because of the high level of demand revealed by the numbers of applications received for each call for proposals. The issues are many and multi-faceted, such as selection, monitoring, management, information dissemination and exploitation of results, but also survival of established networks. The major challenge lies in fact in the definition of EC research programmes and their integration with national ones. As a matter of fact, the new Treaty on the European Union, better known as the Maastricht Treaty, when ratified, opens new possibilities in relation to a novel EC competence in health. The potential enlargement of the EC, i.e. the negotiations with Austria, Finland and Sweden to join, the European Economic Area, close collaboration with Central and Eastern Europe, gives new geographical dimensions.

Our enriching experience of promoting collaboration in the biomedical engineering community at European level enables us to be optimistic about the future. One caveat, though: there is no doubt that the approach to biomedical research at European level should undergo a thorough review, in particular with regards to appropriate financial means and more varied support mechanisms. In such an evolution, the value of maintaining, even protecting, the concerted action system should not be overlooked; its originality and its flexibility are at the same time its strength and its weakness. We hope that the chapters in this volume will contribute to a better recognition of this approach.

Prof. Dr. Ir. Jan EW Beneken

Eindhoven University of Technology (NL)

Chairman of COMAC-BME

Dr. Viviane Thévenin

Commission of the European Communities DGXII-E-4

Secretary of COMAC-BME

(*) Commission of the European Communities

“The Research Networks built by the MHR4 Programme”

Authors: P. Laredo, B. Kahane, J.B. Meyer, D. Vinck

Research Evaluation EUR 14700 EN

Luxembourg: Office for Official Publications of the European Commission, 1992

(**)It has been estimated in the order of 5% of the total research expenditures in the fields covered by the EC programme.

Methods : A large international study was undertaken to compare 9 ECG and 6 vectorcardiographic (VCG) computer programs using 1220 clinically validated cases. The same ECGs were also read by 9 cardiologists, 8 of whom analysed the ECG and 5 the VCG. The following diagnostic groups were included : normals (N=382) ; left (N=183), right (N=55) and biventricular (N=53) hypertrophy ; anterior (N=170), inferior (N=273) and combined (N=73) myocardial infarction ; combined infarction and hypertrophy (N=31).

All individual program and cardiologist results were compared with the “truth”, based on ECG independent evidence, while all programs were also compared with the combined interpretations of the cardiologists.

Results : The median specificity of the ECG programs was 91.3% (range, 86.3% to 97.1%) against 80.9% (range, 71.4% to 86.6%) for the VCG programs (P<0.001). Corresponding values for the cardiologists were 96.0% (range, 92.7% to 97.6%) for the ECG and 80.6% (range, 73.8% to 97.2%) for the VCG. The median sensitivities for left and right ventricular hypertrophy, and for anterior and inferior myocardial infarction were 55.7%, 32.7%, 74.1% and 65.1%, respectively, for the computer programs versus 63.4%, 48.5%, 82.9% and 73.3%, respectively (P<0.02 for all four), with equal or lower rates of false positives for the cardiologists. However, programs with the best performance reached almost equal levels as the best cardiologists.

Programs which used statistical methodology for diagnostic classification generally had a higher diagnostic accuracy than the deterministic programs when compared with the “truth”, but the study design may have favored this outcome.

Combined results of programs and of cardiologists were in almost all cases more accurate than those of the individual programs and cardiologists. The combined program and the combined cardiologists agreed in 87.5% of the cases, which is almost as high as the highest intra-observer reproducibility of the cardiologists (median : 82.4% ; range, 73.6% to 90.8%).

Conclusion : The present study shows that some ECG computer programs perform almost as well as the best cardiologists in classifying 7 main diagnostic entities. However, the study also shows that other programs could be improved considerably.

A set of 79 European clinical and 13 blood test data was collected in each EC and COST country. Twenty-three other clinical data were tested on 400 cases. A network of over 128 centres throughout Europe collected 9500 cases according to the protocol. These were entered in a relational database, analysed in 2 centres and distributed to the collectors at intervals pro rata to cases supplied. The 16 diseases causing >1% jaundice in Europe were defined. They were described numerically in terms of the frequencies of occurrence of their symptoms in 100-1500 cases per disease. The most useful diagnostic items were identified. Similar descriptions were made on their 38 sub-diseases. The database covers adequately at least 45 disease conditions. The agreement among 4 observers examining a case according to the protocol was measured on 111 doctors in 8 countries. It was consistently 84-89% regardless of language. Norms for the 12 common blood tests used in diagnosing jaundice were based on the results of 75,000 tests. Normal ranges were obtained on 220 controls (11 centres) and laboratory variation on 6 standard samples tested in 22 centres. A problem in standards was discovered. Audit feedback on their cases in comparison to the database as a whole was provided to the centres, listing missing data, mix of diseases, symptom frequencies and the diagnostic accuracy of the program on their cases (a pan-European audit), and summaries of their cases. The use of the protocol and of feedback to the observers improved the diagnostic quality of the data by 12%, the diagnostic accuracy of the doctors by up to 50% and the omission rate of the data three-fold. Diagnostic programs were prepared by Bayesian, pattern-recognition, likelihood ratio, neural net and knowledge-bases techniques. The crude Bayesian version based on quality cases achieved 72% accuracy. Circulated for field test it attained 50% while a trial algorithm reached 75% (106 cases reported by 12 centres to date) Neural net also outperformed Bayes. The threshold for assessment of the value added by diagnostic technology was reproducibly set by computed diagnosis. The added value of each blood test was demonstrated. The residual scope for new technologies was also established, but may be affected by refinement of computed diagnosis.

This Concerted Action has dealt with Objective Medical Decision Making in relation to Acute Abdominal Pain. Over 450 clinicians and scientists in 64 institutions in 19 different countries have participated in a network of collaborating centres, along with input from 18 national and international societies. Agreement has been reached (after wide consultation with the above participants) concerning a minimum dataset of information to be collected from patients presenting to hospital with acute abdominal pain, together with definitions of terminology for each clinical feature and criteria for diagnosis of each specific disease. On this basis a data collection instrument (a structured proforma) has been developed and translated into most major European languages for the purposes of quality controlled, reproducible data collection.

Using the above, a database of clinical information, strictly controlled for quality, concerning 15,000 acute abdominal pain cases, has been collected. This dataoase, in its scope, extent, and quality control, is unique.

Immediate benefits have occurred within the institutions participating in the project. There is evidence that institutions associated with the project have (when compared with unaided baseline or national figures) achieved the following benefits:- * Reduction of residual diagnostic error rate by 40% * Reduction in unnecessary operation rate by two fifths * Reduction in perforation rate in appendicitis cases by half.

Longer term benefits have either been obtained or are now available for the European Community in terms of:- The existence of an agreed reproducible terminology for the disease area (acute abdominal pain) in question; the creation of a “language independent” computer program to aid objective medical decision-making and clinical audit; the development of an EC wide multinational research team from groups of scattered workers; the creation and distribution of decision-support materials, structured proformata, teaching video-tapes and computer programs widely throughout the EC: the availability of a database of information, strictly controlled for quality, for further clinical research and for evaluation of further decision-support technology in the future.

The first major achievement of the present project is having finalised a most difficult multi-centre study protocol. The project has first been running as a pilot study; this has shown clearly that the question posed was scientifically relevant and approachable from the practical point of view. Experience learned from this pilot phase, has permitted to adapt practical aspects that were considered too difficult by a number of centres. The final protocol that emerged out of this learning period has proven to be rather good as judged from comments at international meetings and symposia devoted to the topic. That the project is feasible was shown by inclusion of almost 1600 patients in an 18 month period. A second achievement is the new format to bring in the data. Although sheet forms are available, data can be entirely brought in by computer and the information can be sent to the coordination centre either by post, electronic mail or by EARN. A third achievement is that the techniques to record blood pressure have largely been standardised and that the reading of the data can be transferred either to a MS-DOS or a MacIntosh computer.

The Concerted Action analysed the clinical problems, identified suitable analytes, and considered sites for continuous in vivo monitoring. As a result its activity focused onto subcutaneous glucose monitoring for diabetes, and intravascular oxygen and ion monitoring for critical care. Common standards for the evaluation and use of continuous invasive glucose sensors were agree. Device strategies were formulated, defining the necessary characteristics and matching them with available technologies. The need for new technology was identified and the development of these systems was promoted, with particular attention to packaging. Recent developments in non-invasive methods were critically evaluated. Clinical testing of sensors was organised and the need for new physiological information identified. An international centre and core of excellence in Europe was established. The practical achievements of the Concerted Action were widely published and summaries appear in the proceedings of the final workshop (Danielsson & Hakansson, Abstracts of Workshop at Snogeholm, Sweden, Oct 1-4. 92 pp.1991) and the book “In vivo chemical sensors: recent developments” (ed. A P F Turner & S J Alcock, Cranfield Press, Bedford 1992). The overall conclusions (summarised in the present report) are published in full in the book “Chemical sensors for in vivo monitoring”, (ed. A P F Turner, JAI press Ltd. 1993). Information was disseminated throughout Europe and internationally. An internationally accessible database was set up.

The collaboration and exchange of information resulted in fabrication and testing of new devices for in vivo monitoring, with particular advances in glucose sensors.

1. Agreement on common protocols for patient examination and data gathering.

2. Development of standardized methods, calibration procedures and protocols for the determination several parameters using ocular fluorometry.

3. Development and testing of specially designed softwares for three main areas of clinical measurement: anterior segment, lens, and blood-retinal barrier.

4. Establishment of a data base of normal values for the different ocular fluorometry tests.

5. Demonstration that ocular fluorometry measurements: anterior segment procedures, native lens fluorescence and blood-retinal barrier permeability, may be performed reliably and in a reproducible manner in different centers and the results pooled. Establishment and consolidation of an European Clinical Netwok of Ocular Fluorometry - E.C.N.O.F.

6. Publication of a Manual of Ocular Fluorometry.

7. First steps of an Atlas of Ocular Fluorophores.

8. Prototype development and comparisons with available instrumentation in the area of light scattering measurements in the aqueous, cornea and lens.

9. Evaluation of the possibilities offered by spectral analysis of the native fluorescence of the cornea, lens and retina. Demonstration of the immediate clinical interest of measurements of corneal and lens fluorescence, particularly in diabetic patients. A simple, totally noninvasive procedure for measuring corneal fluorescence may become a retinopathy screening in diabetic patients. This may have major health impact.

10. Prototype development directed to improve axial resolution led to the conclusion that a target-oriented modification of existing confocal scanning ophthalmoscope is the best option to improve axial resolution for the purpose of ocular fluorometry measurements.

Osteoporosis is the most common bone disease in the Western world. It is defined as an age-related bone loss resulting in increased susceptibility to bone fracture. Because prevention and therapy are now possible, detection of patients at risk is essential.

Progress in bone mass measurements has been very marked during the last 10 years, many regions of interest can now be measured precisely and accurately. However, there is no uniformity in reporting and there are great problems in comparing results from one centre to another. The different manufacturers pursue various strategies for the determination of bone mineral density (BMD) with the hardware and software available for densitometry. The measured values are not directly comparable without consideration of the examination modalities.

In July 1990, a European Concerted Action on Quantitative Assessment of Osteoporosis was started to stimulate and coordinate the research for this particular problem. In the research group was incorporated an already existing Working Group on Bone Fracture Analysis using Vibration Technique.

The purpose of the concerted European research action was to improve comparability of bone mass measurements between machines, measurement sites and centres, to establish normative data, and to find out which techniques and regions are the most sensitive and specific for the diagnosis of osteoporosis. It is therefore necessary to adhere to common examination modalities in order to reduce to a minimum technician error.

The main achievements were :

- The establishment of a working relationship between basic researchers, clinicians and companies interested in quantitative assessment of bone mass and bone density.

- The development of COMAC-BME reference materials known as the European Spine Phantom (ESP) and the European Forearm Phantom (EFP).

- The production and agreement of guidelines for standardization of measurements, definitions (precision, accuracy, constancy and linearity), primary quality control, COMAC-BME phantom cross calibration, measuring sites, regions of interest (ROI) and data reporting.

- Based on 823 ESP and EFP phantom measurement forms, it is now clear after statistical analysis that there are not only important differences in bone density values between instruments of the same type and brand from different manufacturers, and between different techniques, but that significant differences in precision, accuracy and stability have been found which could lead to important clinical misinterpretations.

- The development of procedures and equations for interconverting the results of dual X-ray absorptiometry on the equipment of one manufacturer in conjunction with measurements made on the machines of another manufacturer.

- 6905 bone density data were received at the statistical centre on a normal European population and patient groups: spinal osteoporosis, thyroid excess, hip fracture, hyperparathyroidism and corticosteroid treated cases. All these data were collected in a standardized way on instruments calibrated with COMAC-BME European Spine Phantom (ESP) and European Forearm Phantom (EFP). These data are not yet analyzed, results will be available early 1993.

- The European phantoms and the European guidelines are at present used as a research tool in Japan (Prof. Orimo) and in the USA (Prof. Genant).

- A major achievement is that the manufacturers from the USA and Europe, of dual energy X-ray absorptiometry equipment (DXA) (USA: Lunar, Norland, Hologic; France: Sopha) and quantitative computer tomography (QCT for the spine, Siemens, IGE and Philips) and for the forearm (Stratec and Densiscan) have given their collaboration and expressed their willingness to adapt their instrumentation along the lines of the research results which will come out of this COMAC-BME project.

- Subgroup COMAC-BME II 2.6 Monitoring Fracture Healing, concentrated their activities on intact bone quality assessment and osteoporosis. Their results dealing with new techniques, experiments, studies on bone properties and the correlation with measurement parameters are published in “In vivo assessment of bone quality by vibration and wave propagation techniques, part II, 1992” (G. Van der Perre, G. Lowet, A. Borgwardt Christensen (Editors)).

During the three and a half year covering the period 1989-1992, thanks to the support given by COMAC/BME/EEC for a Concerted Action on Positron Emission Tomography new developments in this field and in interlaboratory collaboration were made possible. Up to nearly 30 PET Centres participated in the programme which was both methodological and clinical. The main results were the following : In Instrumentation and radiochemistry intercomparison of technics, standardizations and protocols led to general agreements allowing comparable results to be obtained. This is particularly important since in the future various centres will work with common clinical protocols. The modelling approach has led also to interesting results in comparing the various methods of measuring cerebral and myocardial blood flow and in studying the effect of tissue heterogeneity on the accuracy of biological parameters estimation.

In Neurology and Cardiology multicentre studies of FDG metabolism in Alzheimer's disease and myocardial viability in coronary artery disease were established. The preliminary results obtained demonstrate that a large scale programme at the European level is possible.

In Psychiatry after an estimation of the European potential, efforts were given in psychopharmacology and brain metabolism.

Finally in Oncology which is a field of choice for the emergence of diagnostic tests the efforts were focused on the search of proliferation indicators and sugar or amino-acids metabolism as an estimation of tumour grade severity and response to treatment.

Information between Centres was provided by regular publication of a Newsletter. Special issues of scientific journals published the main results in Psychiatry and Instrumentation (J. Neural Transmission, Eur. J. Nuc Med., Amer. J. Nuc. Med., J. Med. Prog. Technol.). Publications resulting from collaboration between centres were accepted in high level scientific journals in Chemistry and Medicine (J. Lab. Cmpds. Radiopharm, Appl. Rad. Isot, J. Neuropsych.). Proceedings of workshops on the dopaminergic system, protein synthesis and radiochemistry were published by Kluwer Acad. Publ., Nuclear Medicine series. All these results indicate that a real concertation exists now between the European PET Centres and many projects for the future are the result of a common will.

(a) Established links between active groups within the Electrical Impedance Tomography community in Europe.

(b) Facilitated the development of data acquisition systems for Electrical Impedance Tomography through group collaboration.

(c) Developed a standard resistor phantom and data collection protocol for assessing the performance of data acquisition systems.

(d) Encouraged the development of various approaches to image reconstruction

(e) Explored the uses of Electrical Impedance Tomography in physiological and clinical measurement.

(f) Encouraged development of electrodes for Electrical Impedance Tomography.

(g) Developed the definition of a standard for data formats in Electrical Impedance Tomography.

During the Concerted Action on Automated Cytogenetics the collaborating network has: (1) improved the performance and specifications of automatic metaphase finders, (2) developed new and more efficient techniques for segmenting metaphases into isolated chromosomes, (3) developed new and more efficient procedures for features extraction and chromosome classification, (4) developed alternative hardware and software for automated cytogenetic analysis, (5) developed prototype instrumentation for automated molecular cytogenetic analysis, (6) tested European systems for cytogenetic analysis that are commercially available, and (7) made these innovations available to European industry, which is currently leading the world market in systems for automated cytogenetics.

The aim of the Concerted Action was to advance Biomagnetism in Europe and to maintain the lead that Europe had in this field. Biomagnetism is one of the fields where Europe played and continues to play a leading role. This is partly due to concentrated national research efforts. Biomagnetism enjoys National Research Project status in Italy, Germany and Finland and large scale state-of-the-art facilities exist in a number of locations in these countries.

The full development of biomagnetism as a diagnostic tool is a major task requiring the cooperation of scientists of several disciplines (e.g., cardiologists, neuro-electrophysiologists, mathematicians, engineers and physicists). The high-tech equipment such as multichannel magnetometer systems, computers for imaging techniques, dataprocessing, and the reconstruction of the sources necessitate substantial financial inputs and staff. Hence, each of the European biomagnetism groups can only deal with a few aspects of the subject. Pooling of knowledge, sharing of tasks, standardisation, testing of instruments, comparison and evaluation of methods and results as well as education of scientists were the aims of the concerted action expressed at a general level.

Especially the pooling of knowledge has been succesfully started within the concerted action. The training of scientists was carried out within the framework of COMETT II and the construction of a database on multiple sclerosis and focal epilepsy plus a database with electrophysiological a-priori information will be started within AIM.

The concerted action led to the following publications: The first two Biomagnetism Supplements to Clinical Physics and Physiological Measurements were published in 1991 and a third will follow in 1992 as will a book on epilepsy. A special issue of the International Journal on Cardiac Imaging was devoted to Biomagnetic Imaging for ablation of cardiac arrhythmias. A bulletin is sent twice a year to more than 1300 addresses of scientists who expressed their interest. Several inspiring workshops have been held, some are videotaped. A practical PC course on the Boundary Element Method was given and all the participants have taken the programmes home. A data base for literature is completed (i.e., it is up-to-data). Cooperative research has been carried out. Individual grants have been supplied to enable this. Computer programs have been distributed. It was agreed that full standardization would be premature, because it would stifle initiative. A common data format and programs to convert these data formats will be available in the nearest future. Experts in Biomagnetism have given talks as invited speakers at important medical conferences and the costs were paid for by the CA. A formal standpoint was formulated at a meeting of experts regarding the source localization accuracy of EEG and MEG; this standpoint is published in the Journal Electroencephalography and Clinical Neurophysiology, 82, 1992, Editorial: A consensus on reletive merits of EEG and MEG, pp. 317-319. An E-mail based computer network is established and is used for communication between all groups. A COMETT II and an AIM programme are supported by the EC. In short, a network on biomagnetism has been established in Europe. E8ach biomagnetic centre within EC and cost countries was a participant. All European industries which have heavily invested in the development of biomagnetic equipment (i.e.,- Siemens, Philips, Dornier, BTI) were actively participating in our concerted action. The cooperation with industry is appreciated, for example several experts from outside Europe have been invited to our workshops by the industrial partners to share their knowledge with our members.

The programme dealt with the application of new technologies for diagnosis and rehabilitation of hearing impairment. The principal emphasis of the programme was on signal processing hearing aids. Our priority areas of application were the problems of hearing impairment in the neonate and in the elderly population. At the beginning of the programme we held the first international conference on signal processing hearing aids, and a follow-up workshop was held at the end of the programme. The first meeting reviewed the state of the art in hardware and software, and created a network of active laboratories in Europe. A specific plan of collaborative research was formulated, resulting in the development of a prototype hearing aid for the profoundly hearing impaired, using a feature extraction approach. The device is currently undergoing evaluation in several centres. A workshop on early identification of neonatal hearing impairment established a network of active groups and identified the measurement of otoacoustic emissions as providing the best basis for an automated screening device for neonates. We have tried to solve some of the problems associated with patent rights for using this technology and work on developing screening devices is now under way in several participating institutes. We have held the first European meeting on hearing impairment in the elderly and established a network of active groups working on this topic. A meeting on auditory neuromagnetic responses identified the major European groups working in this field. These groups will continue to meet under the concerted action on neuromagnetism. Finally, a meeting on histopathology of the human temporal bone focused the activities of participating laboratories on studies of early development and ageing, and led to the setting up of a multicentre evaluation of the temporal bone from a 77 year old patient. Our concerted action has published six volumes of proceedings in Acta Otolaryngologica, containing a total of 148 research and theoretical papers. These proceedings have been distributed widely inside and outside Europe.

The Concerted Action EUROBIOMAT -Haemocompatibility- provided research laboratories either from industry or university, authorities for certification and control, and organisations for standardisation with a large collection of detailed descriptions of test methods covering all aspects of haemocompatibility of biomaterials (Book of Standards). A Network of European Test Centres has been established in order to evaluate the limitations of individual test procedures and to qualify and certify biocompatible materials and surfaces. Six different Reference Materials (tubes and sheets), all of them already in clinical use, were purchased and distributed to the collaborating centres in order to achieve a large series of material data obtained from identical surfaces. New and better haemocompatible biomaterial surfaces have been developed as well as disposable PVC-tubes with alternative plasticisers with an essentially decreased migration rate and lower toxicity.

This paper describes the main achievements of the Concerted Action on “Technology and Blindness”, active from 1988 to 1991. After a brief introduction to the methodology used to meet the multidisciplinary objectives of the project, the main results and conclusions are presented with reference to the discussions held in several workshops and in the coordinated research projects. The fundamental effect of the Concerted Action as a catalyst of activities in other European and national research projects is emphasized.

A network of interlaboratory collaborations involving approximately 270 scientists and clinicians from more than 100 institutions was set up in the area of clinical hyperthermia. Main objective was the improvement of technology related to hyperthermia treatment and stimulate a concerted clinical action on a european level. Areas of research covered electromagnetic and ultrasound heating, invasive and non-invasive thermometry, modelling and treatment planning, guidelines for quality assurance. We report on the results and the prospects of the network on the period July 1989 - September 1992 covered by CEC contracts MR*4/0204/B and 1VLR*4/0306/B.

Skeletal implants are biocompatible synthetic materials and structures utilised for the repair, augmentation or replacement of natural tissues and joints in orthopaedic and dental prostheses. In recent years the development of implants as artificial joints for the replacement of arthrotic hips has provided a major clinical advance in the treatment of arthritis, with nearly half a million patients on a world-wide basis (about half in Europe) benefiting annually from total hip arthroplasty. Parallel progress has been made with the treatment of other arthrotic joints, particularly of the knee, with approximately 400,000 patients treated per year by a joint replacement procedure. However all the current joint prostheses suffer from a finite lifetime before they need to be replaced, due to a basic mismatch between the implant and the adjacent tissue (bone) at regions of fixation (ranging from a mean of ~10 years for a 65+ year old patient to less than 5 years for a 45 year old patient), which leads to the need for a one or more revision operations. Based on the available statistics of prostheses lifetimes, the number of revisions required for existing joint replacements based on current technology will continue to escalate throughout Europe, with both a catastrophic effect on the total health care budget and a continuing absence of a suitable treatment for younger patients. The recognition of this major problem led to the formation of this concerted action in skeletal implants in 1989, with Professor Bonfield as project leader (co-ordinator). The following general achievements have resulted from the concerted action:

i) Methods have been developed for the standardisation and evaluation of retrieved skeletal implants on an European scale, as a basis for determining the mechanisms which result in significant prostheses failure.

ii) An European network has been established of laboratories involved in critical aspects of the underpinning science for the development of second generation skeletal implants, with an enhanced lifetime in the patient. Such optimised implants have application, not only in replacement joints, but in a wide range of procedures, such as the treatment of bone tumours, repair of cartilage lesions, ligament and tendon replacement, bone fracture fixation, maxillo facial reconstruction, spinal disc and vertebra replacement and dental implants.

The particular achievements are summarised as follows:

i) Implant retrieval

a) Appropriate analysis methods for implant retrieval were established.

b) A comparison with other protocols and standards was initiated.

c) A consensus as to critical parameters required for implant evaluation was consolidated.

d) A circuit was initated for evaluating the same retrieved specimen in different European laboratories utilising a range of expertise.

ii) Innovation of second generation implants

a) A European multi-disciplinary forum and laboratory network was established.

b) The conditions required at the tissue implant interface for long term stability were defined.

c) A consensus on the merits of novel bioactive materials, including hydroxyapatite ceramics and composites and modular systems, combined with an appropriate biomechanical environment, to provide optimised implants was approached.

The concerted action established a pool of primarily computer-based assessment and rehabilitation programmes for the treatment of brain-damaged patients. This pool contains the following assessment procedures: batteries for the diagnosis of attention disorders, visual hemi-neglect, disorders of short-term visual memory and procedural learning, aphasia type and severity, naming disorders and acalculia. Normative data have been collected for all test batteries; standardization has been achieved for the attention and aphasia test batteries. The following rehabilitation programmes were developed, adapted for the respective languages and partially evaluated in multi-centric studies: training programmes for attention disorders, visual hemi-neglect, everyday memory disorders (imagery as a therapeutic mnemonic), several aphasia therapy programmes and a selfadapting training programme (expert system) for the treatment of acalculia. This pool of programmes provides the basis for the development of a European Standardized Computerized Assessment Procedure for the Evaluation and Rehabilitation of Brain-Damaged Patients.

A Database on medical devices, to be used in the member countries has been developed. The structure developed enables the users to introduce and present data on makes, models, most important properties, local standards, local regulations, a short description, hazards, alerts, literature, etc. Procedures are developed to gather the data in a concerted action with experts from other member countries.

By using this program a considerable time can be saved compared with local, individual activities on the setting up of a national database on medical devices in the member countries.

The contents and structure of the database can easily be modified to fulfil the requirements of the users, hospital staff, suppliers, governmental or European organizations.

Evaluation reports and quality guidelines have been distributed and made accessible in all the member countries.

Procedures and protocols have been exchanged to enable the institutions to use the same methods in testing and evaluating equipment. The methods are used in comparative studies, acceptance testing or even in maintenance programs in hospitals.

This paper summarizes the main objectives, areas of collaborative research and scientific achievements of the EC Concerted Research Project “Tissue Characterization by MRS and MRI” (1988-1992). In the field of MRI the Project developed original protocols and test objects for performance assessment and quality control of clinical equipment; b) an image conversion software package for interlaboratory exchange of MR images; c) pilot data bases of in-vitro and in-vivo tissue relaxation times. In the field of MRS, the Project proposed an original test system for performance assessment and quality control of clinical and experimental equipment. Test objects for assessing volume and slice selection signal localization were designed, constructed and optimized in a series of international trials. A multi-center evaluation of different data analysis procedures was also carried out on a set of complex valued in vivo NMR time domain test signals, in order to make quantitative MRS results from different Centers more comparable and reproducible.

The major achievements of this Concerted Action can be summarised as follows: Techniques and algorithms for investigation into human gait modelisation and functional evaluation of walking recovery in paralysed patients. Creation of a European network for multicenter clinical trials of the assistive devices for restoration of walking in patients with high level spinal lesions, using the same methods and protocols for patient selection, training, device adaptation and patient assessment. Research into electrodes (surface and implantable) and stimulation patterns for Functional Electrical Stimulation (FES), supported also by experiments on animals; development of models for control strategies in walking by FES and their preliminary validation on patients. As direct effect of the Concerted Action, more than 200 paraplegic patients in Europe are benefiting of advanced mechanical orthoses, and almost 20 are testing hybrid systems with FES. Investigation into the ergonomics of wheelchairs and into its influence on design parameters, construction aspects, prescription criteria and fitting process. Study of technical testing techniques and methodologies and investigation into their comparability in view of promoting implementation of international standards. Development and validation of methodologies for consumer testing of wheelchairs. Identification of obstacles and solutions for wheelchairs testing information disclosure at European level so as to ensure coherence with either the ISO standards or the European Handynet information system. Definition of a preliminary agreement among the 6 European Wheelchair Testing Institutes to circulate the Test Reports, according to common guidelines, defined in the frame of the Concerted Action (particularly important in view of the 1992 free market), and publication of the first pilot volume including such Test Reports of wheelchairs tested in 1990 and 1991, provided by each Institute. Promotion of an infrastructure for ensuring that the expertise of the Testing Centres be exploited in the frame of the CEN Standardisation activities which are starting by the end of 1991.

In the period 1985-1990, the Commission of European Communities (Medical Health Research - COMAC-BME) supported a concerted action on “Monitoring of Fracture Healing”, involving 12 centers in 9 countries. The project group concentrated mainly on mechanical vibration analysis. The nature of tibial vibrations and the correlation between resonant frequencies and mechanical stiffness are now well documented. The sensitivity of resonant frequencies to fracture healing was assessed by analytical and experimental modelling as well as animal experiments. Influences of soft tissues on the in vivo vibration behaviour were evaluated. Low cost instrumentation was developed, and the reproducibility of in vivo measurements was examined. Finally clinical fracture healing monitoring by vibration analysis has been proven to be feasible under well defined conditions.

Recently, the scope of the group has been extended to “in vivo assessment of bone quality by vibration and wave propagation techniques” including ultrasound and sonic wave propagation analysis as techniques and e.g. osteoporosis diagnosis, evaluation of consolidation after bone elongation and assessment of prosthesis loosening as clinical applications. Preliminary results are discussed in the review.