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Eur J Nucl Med Mol Imaging (2008) 35:1749–1757
DOI 10.1007/s00259-008-0861-7

 SOCIETY COMMUNICATION


European Science Foundation calls for more and better
medical imaging research
Arturo Brunetti & Alberto Cuocolo




The European Science Foundation (ESF) has called for                is needed if Europe is to realise the full potential of new
greater collaboration across Europe on research on medical          technological developments and remain globally competi-
imaging. In October 2007, the medical section of the ESF,           tive in this field. Medical imaging is one of the fastest
the European Medical Research Councils (EMRC), pub-                 growing areas within medicine, both in the clinical settings
lished a science policy briefing on “Medical Imaging for            in hospitals and in research and development. According to
Improved Patient Care”, based on a workshop attended by             the experts, imaging is making important contributions to
key experts in the field of medical imaging. This policy            preventive medicine and early diagnosis, whilst new
briefing emphasises the great potential of medical imaging,         imaging technology could result in improved and cost-
outlines European issues and challenges and presents policy         effective healthcare. But, says the ESF, to obtain the
recommendations. Within the briefing, the ESF claims that           maximum benefit from these exciting advances, research
medical imaging research in Europe is fragmented and that           needs to be more collaborative than at present. The science
closer cooperation between doctors, scientists and industry         policy briefing contains a number of key recommendations
                                                                    that will lead to more and better research into medical
                                                                    imaging throughout Europe: 1) improved collaboration
                                                                    between universities, between imaging specialists and other
A. Brunetti : A. Cuocolo (*)                                        scientists, and better ways to bring together different types
Department of Biomorphological and Functional Sciences,             of imaging to provide superior information; 2) the
Institute of Biostructures and Bioimages of the National Research
Council, University Federico II,
                                                                    establishment of large interdisciplinary research groups
Naples, Italy                                                       with access to long-term funding; and 3) better collabora-
e-mail: cuocolo@unina.it                                            tion between academia and industry.




                                                                                                             DO00861; No of Pages
1750                                                                                        Eur J Nucl Med Mol Imaging (2008) 35:1749–1757



Medical Imaging for Improved Patient Care

Foreword                                                                   Introduction

The rapid development in medical research produces a                       Medical imaging is one of the fastest growing areas within
continuous stream of new knowledge about disease processes,                medicine at present, both in the clinical setting in hospitals
new therapeutic targets and the complex relationship between               and in research and development (R&D).
a person’s genome and his/her related risk for disease. New                   Some important benefits from an increased research
technology is being developed for all aspects of patient care              effort in medical imaging are expected in:
and the potential benefits of personalised medicine is gaining
acceptance.                                                                Improved Patient Care
   Medical imaging can now play a central role in the global
healthcare system as it contributes to improved patient
                                                                           &   personalised medicine with individually tailored treatment
outcome and more cost-efficient healthcare in all major
                                                                           &   more evidence-based decision making within healthcare
disease entities. More and better research in medical imaging
                                                                           &   less complications during and after surgery
is needed in Europe to increase our knowledge about disease
                                                                           &   better understanding of the effect of treatments on diseases
processes and therapy management with the long-term goal
of improving the health of European citizens.
   The European Science Foundation’s medical section, the
European Medical Research Councils (EMRC) engaged in
this science policy activity because medical imaging plays a
role of everincreasing importance at all levels of the healthcare
system. EMRC assembled a group of European high-level
experts in this field and conducted a Strategic Workshop in
November 2006 to put a focus on research in the wide area of
medical imaging, to analyse the status quo of medical imaging
in Europe and to develop a policy for optimal use of research
resources at the European level. Their recommendations are
summarised in this policy briefing. To strengthen Europe’s
position in this truly global scientific field, emphasis has to be
put on an increased collaboration, in particular between
different universities, between imaging specialists and clini-
cians, between academia and industry, and between different
imaging modalities. The establishment of interdisciplinary
research groups of sufficient size provided with access to
long-term funding is a prerequisite to fostering further
development of this research area in Europe.
   The aim of this science policy activity is to develop                   Fig. 1 Multiparametric post-processing procedure and visualization
research-based knowledge on how to use medical imaging                     of brain structures (left) and segmentation for tissue volume measure-
for the benefit of improved patient outcome, sustainable                   ments (right) (courtesy of Prof. Bruno Alfano)
healthcare systems and increased competitiveness in the
                                                                           Improved Health of European Citizens
European medical industry.

John Marks                                       Liselotte Højgaard        &   screening of an entire population, e.g. for breast cancer,
Chief Executive, ESF                             Chair, EMRC                   or targeted subpopulations with increased risk of
                                                                               specific disease entities
The European Science Foundation (ESF) provides a platform for its          &   better assessment of risk factors and better prevention of
Member Organisations to advance European research and explore new              disease
directions for research at the European level. Established in 1974 as an
                                                                           &   shorter time to cure for improved treatment efficacy
independent non-governmental organisation, the ESF currently serves
75 Member Organisations across 30 countries.                               &   less recurrence of disease
www.esf.org                                                                &   decreased mortality and morbidity
Eur J Nucl Med Mol Imaging (2008) 35:1749–1757                                                                             1751


Cost-Efficient Healthcare                                           of different modalities, such as PET and CT, MRI and
                                                                    PET, ultrasound and MRI).
&   more rapid and accurate diagnosis
                                                                (2) standard disease-based protocols for diagnosis and
&   less time to best choice of most efficient treatment
                                                                    follow-up.
&   quicker recovery after surgery
&   shorter hospital stays                                         Traditionally, medical imaging was a tool for noninva-
&   cost-effective use of expensive diagnostic and surgical     sive mapping of anatomy and for detection and localisation
    equipment                                                   of a disease process. However, consecutive to a paradigm
                                                                shift, it has been demonstrated that a wide variety of new
                                                                medical imaging techniques and methods produce impor-
Socio-Economic Benefits
                                                                tant biological information about physiology, organ func-
&   less time out of work                                       tion, biochemistry, metabolism, molecular biology and
&   less need for long-term nursing                             functional genomics (Fig. 1). These new methods combine
                                                                the ability to measure and quantify biological processes
Improved Competitiveness of the European Medical Industry       with the ability to localise the measured entities into a high-
                                                                quality anatomical image. Further, advanced imaging
&   research-based development of new innovative technology     techniques are now used for treatment instead of surgery:
    and products                                                e.g. coronary angioplasty, treatment of aortic aneurysm and
&   focus on user-friendly equipment tailored for cost-         coiling of bleeding cerebral aneurysms. Exciting new
    efficient healthcare                                        advances in medical imaging are based on research in the
                                                                areas of functional and molecular imaging and in the area of
   Medical imaging has an important role in the care of all     development of imaging biomarkers for improved preven-
organ systems and disease entities, and better and increased    tion, diagnosis and treatment of disease (Fig. 2).
medical imaging research may benefit the entire process of
health and disease management, including:

&   prevention
&   individual risk assessment
&   screening targeted subpopulations with increased risk of
    specific disease entities
&   early detection of subclinical disease
&   optimal choice of treatment based on personalized
    medicine
&   image-guided minimally invasive surgery and interventions
&   prognosis
&   non-invasive monitoring of treatment effects for
    response-adjusted treatment in case of poor response
&   patient follow-up to adjust multidrug therapy in chronic
    disease
&   early detection of recurrence                               Fig. 2 Ultrasound assessment of foetal growth and development of
&   decision making tool for early-onset disease treatment      brain structures (courtesy of Prof. Sturla Eik-Nes)
    and monitoring

   Medical imaging covers many different imaging modali-
                                                                   The concept of personalised medicine is based on the
ties: x-ray-based methods such as radiography and Computed
                                                                potential for extensive mapping of the disease biology of an
Tomography (CT), Magnetic Resonance Imaging (MRI),
                                                                individual patient. Based on this information, treatment can
ultrasound (US), nuclear medicine with Positron Emission
                                                                be tailored to the individual patient’s disease biology and
Tomography (PET) and Single Photon Emission Computed
                                                                genetic make-up. Medical imaging research has a crucial
Tomography (SPECT), and several methods in optical
                                                                role to play in the development of better and more
imaging. An important goal is to exploit the synergies of the
                                                                personalised medicine with the important benefits of being
different methods. This might be achieved in two ways:
                                                                non-invasive and offering global anatomical coverage and
(1) correlative approaches, for example hybrid systems          co-localisation of the disease process and the relevant
    and image co-registration software (with image fusion       biological measurements.
1752                                                                                         Eur J Nucl Med Mol Imaging (2008) 35:1749–1757


   The important and exciting progress in biotechnology,                   European Issues and Challenges
nanomedicine and new innovative therapies is in many cases
highly dependent on integration with medical imaging for                   Collaboration, Interdisciplinarity, Pooling of Resources,
successful application into standard clinical practice.                    Industry
   Examples are:
                                                                           For success in this research area it is necessary to create
&    guidance of biopsy sampling (by ultrasound, CT, MRI and
                                                                           true multi- and interdisciplinary research environments
     PET) to obtain a relevant material for the in vitro mapping
                                                                           where medical doctors, physiologists, physicists, chemists,
     of the genetic expression and biology of the individual
                                                                           mathematicians, molecular biologists, computer scientists
     disease
                                                                           and other technologists and technicians work closely
&    guidance of targeted drugs and of gene vector therapy
                                                                           together on the same research projects. These challenges
     and guidance of targeted radiation therapy
                                                                           are certainly not restricted to Europe and can only be
&    guidance of stem cell therapy
                                                                           overcome through long-term funding of large research
&    monitoring of cell differentiation and improved function
                                                                           projects. In most cases close collaboration between univer-
     in stem cell therapy
                                                                           sities and major research centres is necessary to obtain the
   At present, medical imaging research in Europe is frag-                 wide range of high-level competence, to achieve a research
mented, and to a large extent financed by industry. As shown in            environment of sufficient size, and to obtain the necessary
the recent report ‘Key figures 2007 on Science, Technology and             funding for infrastructure and large research projects.
Innovation1’, medical, precision and optical instruments is                    A particular challenge is to achieve increased collabora-
twice as R&D intensive and almost 50% bigger in the USA                    tion between imaging specialists (radiologists and nuclear
than in the EU (Fig. 3). Therefore, an increased focus on                  medicine physicians) and the clinicians with knowledge of
research in this area is important for European competitive-               different organ systems and disease entities. The latter
ness. The main goals should be increased public financing and              group also knows the special needs of imaging in relation to
improved cooperation at the European level.                                the disease areas they specialise in and the workflow in
                                                                           clinical departments.
                                                                               Traditionally, medical imaging has been an activity
                                                                           where an imaging specialist makes an educated evaluation
              BERD         VALUE ADDED AS % OF GDP                         of the patient’s disease, based on visual inspection of a
        (Business R&D      (Contribution of each industry to GDP)          limited number of images. However, we now see two
    expenditure as % of
                  GDP)                                                     emerging trends:
                                                                           &     an exponential increase in the number of images
                          EUROPE                                                 acquired for each patient
                                                                           &     the possibility of using the images as raw data for
                 0.56                                      3.08                  quantification in order to measure relevant entities in
                                                                                 organ function, physiology and molecular biology
                0.07 0.50
                                                                              Medical imaging research must address these changes
                                                                           through focusing on Information and Communication
                          USA                                              Technology (ICT) solutions for decision support for
                                                                           radiologists, nuclear medicine physicians and other physi-
              0.81                                                  3.71   cians, and also focusing on improved quantification of
                                                                           imaging results and biomarkers. The latter is also important
              0.19         0.71
                                                                           for longitudinal follow-up of patients and comparability of
                                                                           results between centres in multicentre clinical trials.
                                                                              Initiatives aimed at addressing the need for improved
                                                                           cooperation at the European level, such as the European
       Total high-tech                                                     Institute for Biomedical Imaging Research (EIBIR)2,
       Medical, precision and optical instruments                          should be encouraged. However, it is of benefit to have a
Fig. 3 R&D expenditure for medical precision and optical instru-           variety of different organisational structures to foster
ments - EU27 compared to USA                                               European collaboration of different types and at different

1
  See report published 11 June 2007 at: http://www.eurosfaire.prd.fr/
                                                                           2
7pc/doc/1182348125_kf_2007_prepub_en.pdf                                       More at: http://www.eibir.org/cms/website.php
Eur J Nucl Med Mol Imaging (2008) 35:1749–1757                                                                               1753


levels, keeping in mind that they should be next to                  medical imaging research in particular that national existing
University Hospitals and Research Hospitals.                         regulations are adapted to allow:
    Furthermore, the EC ESFRI – European Strategy Forum
                                                                     &   an easy organisation of good quality clinical research
on Research Infrastructures3 in the first European Roadmap
                                                                         for the benefit of patients
for Research Infrastructures has put emphasis in the
                                                                     &   the protection of the individual patient who is included
EATRIS4 proposal on the need for high performance
                                                                         in a specific clinical study
facilities in medical imaging such as NeuroSpin for brain
imaging.                                                                Clinical imaging research is an area where Europe has
    Collaboration of academia with industry is important,            taken on a leadership role that could be of benefit for the
both to attract funding and to ensure exploitation of R&D            competitiveness of the European industry.
synergies. However, academia should take the lead in                    At the European level there is a need to develop,
defining the research activities based on the dual goal of           coordinate and adopt better systems for evidencebased
improved patient outcome and costefficient healthcare. In            medicine and health technology assessment for recommen-
the long term, this approach will also benefit the compet-           dations of standard practice in medical imaging.
itiveness of the European medical imaging industry through              For better translation into new clinical practice and
a focus on R&D that addresses the patients’ and clinicians’          widespread adoption of new advanced methods, it is
needs and encourages user-friendly equipment tailored for            necessary to establish two important tools at the European
cost-efficient healthcare.                                           level:

Translation of New Health Technology into New Clinical               &   clinical practice standards for optimal use of medical
Practice                                                                 imaging within each specific disease area
                                                                     &   education and training programmes tailored to both
Translation of new technology into new clinical practice is              expert and non-expert users
a significant challenge. Acquisition of new technology                  Many imaging studies and most new methods in
within healthcare is often linked to marketing strategies of         molecular imaging are based on the administration of
the industry and not based on extensive evaluation of which          molecular probes (contrast agents or tracers), currently
new methods may benefit patient care and which technol-              managed as a generic pharmaceutical product by the
ogies have the potential for improving cost-efficiency in the        regulatory bodies. An important limitation for translation
healthcare system.                                                   into new clinical practice is the need for approval of the
   New methods in medical imaging are often adopted                  new drugs from the appropriate regulatory body, in
without sufficient scientific proof; and larger clinical trials      particular for molecules administered in tracer amounts.
with appropriate end-points to prove the benefits should be             Two possibly conflicting trends are emerging for
planned. Examples of relevant end-points are better choice           molecular imaging diagnostic applications:
of treatment and/or improved patient outcome due to
                                                                     &   stricter rules for the approval of drugs and more
information provided by new imaging techniques.
                                                                         expensive clinical trials
   There are, however, some important challenges
                                                                     &   more contrast agents and tracers tailored to specific use
connected to the adoption of strict rules for evidence-based
                                                                         and/or small subpopulations of patients
medicine in medical imaging. Improvements are often
incremental with a more or less continuous process of                   There is the risk that many promising methods with huge
technology improvement and new applications. And when                potential benefit for improved patient outcome will never
there are cases of significant improvements, it has often            be translated into clinical practice because the potential
been argued that the benefit of the technology is self-              market is too small to cover the costs of development.
evident and that study designs with randomisation of
patients to new and old technology is unethical. Industry            Lack of Money and Resources as the Limiting Factor
should be requested to prove, prior to marketing, that new           for Medical Progress
expensive technology is of added value to patient care. It is
of importance for clinical research in general and for               A challenge for the future healthcare system is that lack of
                                                                     money and resources may become the limiting factor for
                                                                     the services offered to the population. One reason is the
3
  More at: ftp://ftp.cordis.europa.eu/pub/esfri/docs/esfriroadmap-   demography arising from the ageing population. Another
report-26092006_en.pdf                                               reason is the wide range of progress in medical research for
4
  EATRIS – European Advanced Translational Research Infrastructure   diagnosis and treatment that is often costly. This challenge
in Medicine                                                          can only be met through the dual focus on improved patient
1754                                                                             Eur J Nucl Med Mol Imaging (2008) 35:1749–1757


outcome and cost-efficient solutions within healthcare            A well-defined problem is the ionizing radiation in the case
systems.                                                          of x-ray and nuclear medicine. There are also concerns
    Medical imaging may become an important contributor           about potential hazards from magnetic resonance when
to obtain this dual goal. Even if new imaging technology is       moving to higher fields and from ultrasound when moving
expensive it may contribute significantly to cost-efficiency      to higher frequencies. Many of the advanced methods
in a labour-intensive healthcare system if the new methods        include injection of new molecular probes (contrast agents,
lead to shorter hospital stays, less use of non-efficient         tracers, nanopeptides) with potential toxicity, side-effects
treatment (surgery, drugs and others), and less recurrence of     and adverse events. Medical imaging research must also
disease. Improved patient outcome will also have an impact        be focused on reducing these hazards and finding the
on the society through reductions in sick leave, disabilities     best compromise between patient safety and potential
and nursing expenses.                                             benefits.
    Cost-efficiency can also be obtained through develop-            This safety assessment issue should be pro-actively
ment of advanced methods in medical imaging into user-            addressed in collaboration between academies, health care
friendly tools that can be applied also by non-expert users       industry and national and EC competent authorities.
at the initial point of care.
    Cost-efficiency for the healthcare system should be
included as a separate end-point for imaging research, and
researchers with competence in how to evaluate economic           Recommendations
measures should be included in the planning of clinical trials.
                                                                  The main recommendation is to:
Medical Imaging as a Research Tool                                1. Obtain more and better medical imaging research in
                                                                     Europe through:
Medical imaging is an important research tool to obtain
new knowledge about disease processes and treatment               &   improved European collaboration, in particular between
targets. Funding of medical imaging research and infra-               different universities, between imaging specialists and
structures is also needed for this purpose. Imaging is a non-         clinical doctors, and between different imaging modalities
invasive and well-suited technique for longitudinal studies       &   establishment of interdisciplinary research groups of
that provides quantitative measures of the disease process-           sufficient size and with access to long-term funding
es. Both in a preclinical and a clinical research setting there   &   improved collaboration between academia and industry
is medical imaging technology (equipment, contrast agents             where research goals are defined by academia
etc.) that will probably never be developed into tools for
routine clinical use on patients, but which still benefit            This is important in order to obtain medical imaging
patient care through the new biomedical knowledge                 research with the necessary size and with true interdiscipli-
obtained.                                                         narity, and for research to be adequately focused on the dual
   Medical imaging also has an important role to play in the      goal of improved patient outcome and cost-efficient health-
context of better and less expensive clinical trials for new      care for the sake of improving European citizens’ health,
drugs and therapies. Imaging may contribute in several            better societies in Europe and improved competitiveness of
ways:                                                             European medical industry.
                                                                     Other important recommendations are to:
&   better inclusion/exclusion of patients
&   better subgrouping of patients                                2. Obtain more evidence-based medicine at European
&   imaging biomarkers may be used as a surrogate                    level through:
    outcome measure for the biological behaviour of               &   health technology evaluation
    different diseases                                            &   validations of standard clinical practice for optimal use
   The importance of this is underlined by the acquisition            of imaging
of large imaging R&D centres by the pharmaceutical                &   socio-economic measure of these new health technologies
industry.                                                         3. Establish appropriate education/training for widespread
                                                                     translation of new technology into new clinical practice.
Safety Issues
                                                                  4. Develop advanced methods within medical imaging
The different imaging modalities present a wide spectre of           into user-friendly tools that can be applied also by non-
potential hazards for the patients and for the environment.          expert users at the initial point of care.
Eur J Nucl Med Mol Imaging (2008) 35:1749–1757                                                                                       1755


5. Plan and fund both short- and long-term research                  Example 2 (early detection of subclinical disease)
   activities:
                                                                     There is exciting research activity with the combination of
&   short-term applied research is necessary for translation
                                                                     PET and functional MRI for the early diagnosis of
    of established new technology into new clinical practice
                                                                     neurodegenerative diseases, with a main focus on Alz-
&   long-term basic research is necessary to develop and
                                                                     heimer’s disease. There are now PET tracers that are
    evaluate new advanced methods, especially in the areas
                                                                     promising for noninvasive detection of Alzheimer plaques,
    of functional and molecular imaging, and to use medical
                                                                     and functional MRI may detect changes in functional brain
    imaging as a research tool to obtain new knowledge
                                                                     activity. For an optimal strategy for halting and/or postpon-
    about disease processes and new innovative therapies
                                                                     ing the development of dementia using cognitive enhancing
                                                                     drugs, mental training and others, it is of great importance
Appendix                                                             to detect the early changes in functional brain activity due
                                                                     to disease progression.
Some examples of promising new possibilities in medical
imaging

To show the wide variety of the possible roles for medical
imaging, a few examples of new, promising methods and
applications are presented.

Example 1 (screening/risk factors/prevention)

Several imaging techniques are promising for the character-
isation of atherosclerotic plaques. A main target is to              Fig. 5 Radiation treatment planning (right) of head/neck cancer based
establish imaging biomarkers for vulnerable plaques and to           on fusion of morphologic and functional information obtained with
                                                                     PET-CT (left) (courtesy of Prof. Liselotte Højgaard)
be able to find the patients that have increased risk of plaque-
induced myocardial infarction and thrombo-embolic stroke.
New imaging techniques and molecular imaging probes in               Example 3 (decision support for choice of treatment/
PET, MRI and ultrasound may detect inflammatory and                  personalised medicine)
other biological processes in the plaques, and may be
developed into a clinical tool for risk assessment of plaque         CT, MRI and PET-guided images are used to target
vulnerability. Plaque imaging may also be developed into             radiation therapy toward the cancer and avoid harmful
tools for monitoring the effect of preventive measures to            radiation to healthy tissue (Fig. 5).
reduce the plaque burden and/or the development into                     Diagnostic imaging tests could be of great value in the
vulnerable plaques as shown in Fig. 4. This may both show            selection of highly expensive treatment procedures: for
the effect of life-style measures as well as drug therapy.           example, new implantable pacemakers and arrhythmia defib-
                                                                     rillators with great potential in the therapy of heart failure have
                                                                     high costs and only a certain subgroup of patients would
                                                                     benefit from this therapy. New imaging techniques such as
                                                                     advanced ultrasound techniques, imaging of cardiac innerva-
                                                                     tion and metabolism may enable the identification of this
                                                                     subgroup of patients that will have an improved prognosis
                                                                     when using this expensive form of therapy.

                                                                     Example 4 (theranostics)

                                                                     Theranostics is a word to describe combined drug therapy
                                                                     and diagnostics5, and is the ultimate concept in targeted

Fig. 4 Coronary artery imaging with multidetector CT and post-
                                                                     5
processing characterisation of coronary plaques (courtesy of Prof.     See ESF Forward Look on Nanomedicine at : http://www.esf.org/
Gabriel P. Krestin)                                                  fileadmin/be_user/research_areas/emrc/Nanomedicine.pdf
1756                                                                                   Eur J Nucl Med Mol Imaging (2008) 35:1749–1757


drug delivery. A molecule targeted for the disease tissue                 As an example, in neurosurgery it is important for the
(e.g. cancer) is linked both to a nonactivated therapeutic             surgeon to avoid damage to the brain structures that will cause
drug and an imaging contrast agent (tracer). In the case of            dramatic functional deficits (limb paralysis, language func-
ultrasound, the drug may be encapsulated in a gas bubble               tion, visual etc.). An integrated protocol of new MRI methods
and after injection the same ultrasound imaging equipment              may, prior to the surgery, delineate important functional areas
may be used first to ensure the correct localisation of the            in the brain and their vital nerve fibre connections. This is of
drug and then activate the drug through bursting of the                great help to the neurosurgeon in the planning of the
bubble with ultrasound waves.                                          operation, and can also be displayed for the neurosurgeon in
                                                                       the operating theatre and updated during the surgical
Example 5 (image guidance of stem cell therapy)                        intervention (tumour resection etc.), using image-guided
                                                                       minimal-invasive surgery with either MRI or ultrasound.
Image guidance may be applied to stem cell therapy on                     Ultimately, further development of robotic imageguided
many levels. First guidance of the delivery and placement              surgery will provide computer assisted tools to facilitate
of the stem cells, then tracking of any migration of labelled          and increase safety of complex surgical procedures in all
stem cells, then monitoring of the cell differentiation for the        fields of surgery.
target organ, and with functional imaging methods, moni-
toring of improved organ function. Imaging techniques that             Example 8 (patient follow-up)
could be used for tracking stem cells in human include
MRI, Nuclear Medicine (PET and SPECT) and possibly                     Cardiac ultrasound has reached a level where the myocar-
ultrasound.                                                            dial wall function can be quantified and 3D visualised.
                                                                       Advanced ultrasound equipment is currently the size of a
Example 6 (monitoring of drug therapy)                                 portable computer and with ongoing research it may reach
                                                                       the size of a cell phone. With further development in the
New imaging methods from PET and MRI produce                           user-friendliness of the advanced methods, it may be
biological information on the growth potential of malignant
tumours. This may be applied to noninvasive monitoring of
the treatment effects of cytostatic drug therapy (usually a
combination of several drugs). FDG-PET 6 can show a
decrease in glucose uptake and different MRI methods can
show reduction in angiogenetic potential. In a case of poor
response, the treatment may be discontinued early on with a
change to other drugs or to other therapeutic methods such
as surgery or radiotherapy. Through this improved managed
care the patient will get fewer adverse reactions, no
ineffective therapy while it will lead to cost savings for
the healthcare system.

Example 7 (image-guided surgery)

Imaging techniques can assist the surgeon both before and
during surgery. Before surgery, image processing tools can
provide realistic previews of the surgical field and of access
pathways, with an interactive 3D anatomic display for
appropriate planning.
   During surgery, image guiding can be valuable for target
localization and detection of boundaries allowing, for
instance, more complete and accurate resection of tumours,
limiting damage to normal tissues.



                                                                       Fig. 6 Doppler ultrasound image (top) of metacarpophalangeal joints
6
  PET scanning with the tracer fluorine-18 (F-18) fluorodeoxyglucose   showing active inflammation (sinovitis). Corresponding MRI study
(FDG)                                                                  (bottom) (courtesy of Prof. Paul Emery)
Eur J Nucl Med Mol Imaging (2008) 35:1749–1757                                                                         1757


possible for patients using multidrug therapy in heart failure      Liselotte Højgaard, Clinic of Clinical Physiology,
to have frequent follow-ups with an adjustment of dose,          Nuclear Medicine & PET, University of Copenhagen,
based on ultrasound image quantification of heart function,      Rigshospitalet, Copenhagen, Denmark
at the general practitioner’s office.                               Juhani Knuuti, Turku PET Centre, Turku University
   Likewise as shown in Fig. 6 below, combined morpho-           Hospital, Turku, Finland
functional imaging approaches (Doppler ultrasound and               Gabriel P. Krestin, Erasmus MC, Department of Radiology,
MRI with conventional and dedicated equipment) can be            Rotterdam, The Netherlands
used for the staged detection of disease activities and for         Christiane Kuhl, Radiologische Klinik der Universität
changes over time in rheumatic diseases, with potential          Bonn, Bonn, Germany
beneficial effects for health expenditures.                         George Laking, Christie Hospital NHS Trust, Manchester,
                                                                 United Kingdom
                                                                    Henrik Larsson, Functional & Diagnostic MR Unit,
Experts Group on Medical Imaging for Improved                    Glostrup University Hospital, Copenhagen, Denmark
Patient Care                                                        Borut Marincek, European Society of Radiology (ESR),
                                                                 Department of Medical Radiology, University Hospital
Chairs                                                           Zürich, Zürich, Switzerland
                                                                    Chrit Moonen, CNRS, Laboratory for Molecular and
Arturo Brunetti (Chair), CNR Institute of Biostructure and       Functional Imaging, University Victor Segalen, Bordeaux,
Biomages, Faculty of Medicine,Medical School, University         France
of Naples Federico II, Naples, Italy                                Hans Olav Myhre, Norwegian University of Science and
   Olav Haraldseth (Chair), MR Centre, Department of             Technology, Trondheim, Norway
Circulation & Medical Imaging, Faculty of Medicine,                 Gabor Rudas, MR Research Centre, Semmelweis
Norwegian University of Science and Technology,                  University, Budapest, Hungary
Trondheim, Norway                                                   Jordi Ruscalleda Nadal, European Society of Neurora-
                                                                 diology (ESNR), Servicio de Radiologia-Neuroradiologia,
Scientific Experts                                               Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
                                                                    Markus Schwaiger, TU Klinikum rechts der Isar,
Silvio Aime, Dpto di Chimica Inorganica, Chimica Fisica e        Medizinische Klinik München, Munich, Germany
Chimica dei Materiali, Facoltà di Scienze M.F.N., Università        George Sutherland, Department of Cardiological Sciences,
degli studi di Torino, Torino, Italy                             St. George’s Hospital, London, United Kingdom
   Paolo G. Camici, MRC Clinical Sciences Centre,
Imperial College London, United Kingdom                          EU Adviser
   Alberto Cuocolo, European Association of Nuclear
Medicine (EANM), Department of Biomorphological and              Tone Woie Alstadheim, Norwegian University of Science
Functional Sciences, University of Naples Federico II,           and Technology, Faculty of Medicine, Trondheim, Norway
Naples, Italy
   Sturla Eik-Nes, National Center for Foetal Medicine,          ESF-EMRC
Department of Gynecology and Obstetrics, University
Hospital of Trondheim, Trondheim, Norway                         Liselotte Højgaard, Chair of EMRC Carole Moquin-Pattey,
   Paul Emery, Academic Section of Musculoskeletal               Head of Unit Thomas Bruhn, Science Officer Gwenaelle Le
Disease, Chapel Allerton Hospital, Leeds, United Kingdom         Cochennec, Administrator

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Nanomedicina6

  • 1. Eur J Nucl Med Mol Imaging (2008) 35:1749–1757 DOI 10.1007/s00259-008-0861-7 SOCIETY COMMUNICATION European Science Foundation calls for more and better medical imaging research Arturo Brunetti & Alberto Cuocolo The European Science Foundation (ESF) has called for is needed if Europe is to realise the full potential of new greater collaboration across Europe on research on medical technological developments and remain globally competi- imaging. In October 2007, the medical section of the ESF, tive in this field. Medical imaging is one of the fastest the European Medical Research Councils (EMRC), pub- growing areas within medicine, both in the clinical settings lished a science policy briefing on “Medical Imaging for in hospitals and in research and development. According to Improved Patient Care”, based on a workshop attended by the experts, imaging is making important contributions to key experts in the field of medical imaging. This policy preventive medicine and early diagnosis, whilst new briefing emphasises the great potential of medical imaging, imaging technology could result in improved and cost- outlines European issues and challenges and presents policy effective healthcare. But, says the ESF, to obtain the recommendations. Within the briefing, the ESF claims that maximum benefit from these exciting advances, research medical imaging research in Europe is fragmented and that needs to be more collaborative than at present. The science closer cooperation between doctors, scientists and industry policy briefing contains a number of key recommendations that will lead to more and better research into medical imaging throughout Europe: 1) improved collaboration between universities, between imaging specialists and other A. Brunetti : A. Cuocolo (*) scientists, and better ways to bring together different types Department of Biomorphological and Functional Sciences, of imaging to provide superior information; 2) the Institute of Biostructures and Bioimages of the National Research Council, University Federico II, establishment of large interdisciplinary research groups Naples, Italy with access to long-term funding; and 3) better collabora- e-mail: cuocolo@unina.it tion between academia and industry. DO00861; No of Pages
  • 2. 1750 Eur J Nucl Med Mol Imaging (2008) 35:1749–1757 Medical Imaging for Improved Patient Care Foreword Introduction The rapid development in medical research produces a Medical imaging is one of the fastest growing areas within continuous stream of new knowledge about disease processes, medicine at present, both in the clinical setting in hospitals new therapeutic targets and the complex relationship between and in research and development (R&D). a person’s genome and his/her related risk for disease. New Some important benefits from an increased research technology is being developed for all aspects of patient care effort in medical imaging are expected in: and the potential benefits of personalised medicine is gaining acceptance. Improved Patient Care Medical imaging can now play a central role in the global healthcare system as it contributes to improved patient & personalised medicine with individually tailored treatment outcome and more cost-efficient healthcare in all major & more evidence-based decision making within healthcare disease entities. More and better research in medical imaging & less complications during and after surgery is needed in Europe to increase our knowledge about disease & better understanding of the effect of treatments on diseases processes and therapy management with the long-term goal of improving the health of European citizens. The European Science Foundation’s medical section, the European Medical Research Councils (EMRC) engaged in this science policy activity because medical imaging plays a role of everincreasing importance at all levels of the healthcare system. EMRC assembled a group of European high-level experts in this field and conducted a Strategic Workshop in November 2006 to put a focus on research in the wide area of medical imaging, to analyse the status quo of medical imaging in Europe and to develop a policy for optimal use of research resources at the European level. Their recommendations are summarised in this policy briefing. To strengthen Europe’s position in this truly global scientific field, emphasis has to be put on an increased collaboration, in particular between different universities, between imaging specialists and clini- cians, between academia and industry, and between different imaging modalities. The establishment of interdisciplinary research groups of sufficient size provided with access to long-term funding is a prerequisite to fostering further development of this research area in Europe. The aim of this science policy activity is to develop Fig. 1 Multiparametric post-processing procedure and visualization research-based knowledge on how to use medical imaging of brain structures (left) and segmentation for tissue volume measure- for the benefit of improved patient outcome, sustainable ments (right) (courtesy of Prof. Bruno Alfano) healthcare systems and increased competitiveness in the Improved Health of European Citizens European medical industry. John Marks Liselotte Højgaard & screening of an entire population, e.g. for breast cancer, Chief Executive, ESF Chair, EMRC or targeted subpopulations with increased risk of specific disease entities The European Science Foundation (ESF) provides a platform for its & better assessment of risk factors and better prevention of Member Organisations to advance European research and explore new disease directions for research at the European level. Established in 1974 as an & shorter time to cure for improved treatment efficacy independent non-governmental organisation, the ESF currently serves 75 Member Organisations across 30 countries. & less recurrence of disease www.esf.org & decreased mortality and morbidity
  • 3. Eur J Nucl Med Mol Imaging (2008) 35:1749–1757 1751 Cost-Efficient Healthcare of different modalities, such as PET and CT, MRI and PET, ultrasound and MRI). & more rapid and accurate diagnosis (2) standard disease-based protocols for diagnosis and & less time to best choice of most efficient treatment follow-up. & quicker recovery after surgery & shorter hospital stays Traditionally, medical imaging was a tool for noninva- & cost-effective use of expensive diagnostic and surgical sive mapping of anatomy and for detection and localisation equipment of a disease process. However, consecutive to a paradigm shift, it has been demonstrated that a wide variety of new medical imaging techniques and methods produce impor- Socio-Economic Benefits tant biological information about physiology, organ func- & less time out of work tion, biochemistry, metabolism, molecular biology and & less need for long-term nursing functional genomics (Fig. 1). These new methods combine the ability to measure and quantify biological processes Improved Competitiveness of the European Medical Industry with the ability to localise the measured entities into a high- quality anatomical image. Further, advanced imaging & research-based development of new innovative technology techniques are now used for treatment instead of surgery: and products e.g. coronary angioplasty, treatment of aortic aneurysm and & focus on user-friendly equipment tailored for cost- coiling of bleeding cerebral aneurysms. Exciting new efficient healthcare advances in medical imaging are based on research in the areas of functional and molecular imaging and in the area of Medical imaging has an important role in the care of all development of imaging biomarkers for improved preven- organ systems and disease entities, and better and increased tion, diagnosis and treatment of disease (Fig. 2). medical imaging research may benefit the entire process of health and disease management, including: & prevention & individual risk assessment & screening targeted subpopulations with increased risk of specific disease entities & early detection of subclinical disease & optimal choice of treatment based on personalized medicine & image-guided minimally invasive surgery and interventions & prognosis & non-invasive monitoring of treatment effects for response-adjusted treatment in case of poor response & patient follow-up to adjust multidrug therapy in chronic disease & early detection of recurrence Fig. 2 Ultrasound assessment of foetal growth and development of & decision making tool for early-onset disease treatment brain structures (courtesy of Prof. Sturla Eik-Nes) and monitoring Medical imaging covers many different imaging modali- The concept of personalised medicine is based on the ties: x-ray-based methods such as radiography and Computed potential for extensive mapping of the disease biology of an Tomography (CT), Magnetic Resonance Imaging (MRI), individual patient. Based on this information, treatment can ultrasound (US), nuclear medicine with Positron Emission be tailored to the individual patient’s disease biology and Tomography (PET) and Single Photon Emission Computed genetic make-up. Medical imaging research has a crucial Tomography (SPECT), and several methods in optical role to play in the development of better and more imaging. An important goal is to exploit the synergies of the personalised medicine with the important benefits of being different methods. This might be achieved in two ways: non-invasive and offering global anatomical coverage and (1) correlative approaches, for example hybrid systems co-localisation of the disease process and the relevant and image co-registration software (with image fusion biological measurements.
  • 4. 1752 Eur J Nucl Med Mol Imaging (2008) 35:1749–1757 The important and exciting progress in biotechnology, European Issues and Challenges nanomedicine and new innovative therapies is in many cases highly dependent on integration with medical imaging for Collaboration, Interdisciplinarity, Pooling of Resources, successful application into standard clinical practice. Industry Examples are: For success in this research area it is necessary to create & guidance of biopsy sampling (by ultrasound, CT, MRI and true multi- and interdisciplinary research environments PET) to obtain a relevant material for the in vitro mapping where medical doctors, physiologists, physicists, chemists, of the genetic expression and biology of the individual mathematicians, molecular biologists, computer scientists disease and other technologists and technicians work closely & guidance of targeted drugs and of gene vector therapy together on the same research projects. These challenges and guidance of targeted radiation therapy are certainly not restricted to Europe and can only be & guidance of stem cell therapy overcome through long-term funding of large research & monitoring of cell differentiation and improved function projects. In most cases close collaboration between univer- in stem cell therapy sities and major research centres is necessary to obtain the At present, medical imaging research in Europe is frag- wide range of high-level competence, to achieve a research mented, and to a large extent financed by industry. As shown in environment of sufficient size, and to obtain the necessary the recent report ‘Key figures 2007 on Science, Technology and funding for infrastructure and large research projects. Innovation1’, medical, precision and optical instruments is A particular challenge is to achieve increased collabora- twice as R&D intensive and almost 50% bigger in the USA tion between imaging specialists (radiologists and nuclear than in the EU (Fig. 3). Therefore, an increased focus on medicine physicians) and the clinicians with knowledge of research in this area is important for European competitive- different organ systems and disease entities. The latter ness. The main goals should be increased public financing and group also knows the special needs of imaging in relation to improved cooperation at the European level. the disease areas they specialise in and the workflow in clinical departments. Traditionally, medical imaging has been an activity where an imaging specialist makes an educated evaluation BERD VALUE ADDED AS % OF GDP of the patient’s disease, based on visual inspection of a (Business R&D (Contribution of each industry to GDP) limited number of images. However, we now see two expenditure as % of GDP) emerging trends: & an exponential increase in the number of images EUROPE acquired for each patient & the possibility of using the images as raw data for 0.56 3.08 quantification in order to measure relevant entities in organ function, physiology and molecular biology 0.07 0.50 Medical imaging research must address these changes through focusing on Information and Communication USA Technology (ICT) solutions for decision support for radiologists, nuclear medicine physicians and other physi- 0.81 3.71 cians, and also focusing on improved quantification of imaging results and biomarkers. The latter is also important 0.19 0.71 for longitudinal follow-up of patients and comparability of results between centres in multicentre clinical trials. Initiatives aimed at addressing the need for improved cooperation at the European level, such as the European Total high-tech Institute for Biomedical Imaging Research (EIBIR)2, Medical, precision and optical instruments should be encouraged. However, it is of benefit to have a Fig. 3 R&D expenditure for medical precision and optical instru- variety of different organisational structures to foster ments - EU27 compared to USA European collaboration of different types and at different 1 See report published 11 June 2007 at: http://www.eurosfaire.prd.fr/ 2 7pc/doc/1182348125_kf_2007_prepub_en.pdf More at: http://www.eibir.org/cms/website.php
  • 5. Eur J Nucl Med Mol Imaging (2008) 35:1749–1757 1753 levels, keeping in mind that they should be next to medical imaging research in particular that national existing University Hospitals and Research Hospitals. regulations are adapted to allow: Furthermore, the EC ESFRI – European Strategy Forum & an easy organisation of good quality clinical research on Research Infrastructures3 in the first European Roadmap for the benefit of patients for Research Infrastructures has put emphasis in the & the protection of the individual patient who is included EATRIS4 proposal on the need for high performance in a specific clinical study facilities in medical imaging such as NeuroSpin for brain imaging. Clinical imaging research is an area where Europe has Collaboration of academia with industry is important, taken on a leadership role that could be of benefit for the both to attract funding and to ensure exploitation of R&D competitiveness of the European industry. synergies. However, academia should take the lead in At the European level there is a need to develop, defining the research activities based on the dual goal of coordinate and adopt better systems for evidencebased improved patient outcome and costefficient healthcare. In medicine and health technology assessment for recommen- the long term, this approach will also benefit the compet- dations of standard practice in medical imaging. itiveness of the European medical imaging industry through For better translation into new clinical practice and a focus on R&D that addresses the patients’ and clinicians’ widespread adoption of new advanced methods, it is needs and encourages user-friendly equipment tailored for necessary to establish two important tools at the European cost-efficient healthcare. level: Translation of New Health Technology into New Clinical & clinical practice standards for optimal use of medical Practice imaging within each specific disease area & education and training programmes tailored to both Translation of new technology into new clinical practice is expert and non-expert users a significant challenge. Acquisition of new technology Many imaging studies and most new methods in within healthcare is often linked to marketing strategies of molecular imaging are based on the administration of the industry and not based on extensive evaluation of which molecular probes (contrast agents or tracers), currently new methods may benefit patient care and which technol- managed as a generic pharmaceutical product by the ogies have the potential for improving cost-efficiency in the regulatory bodies. An important limitation for translation healthcare system. into new clinical practice is the need for approval of the New methods in medical imaging are often adopted new drugs from the appropriate regulatory body, in without sufficient scientific proof; and larger clinical trials particular for molecules administered in tracer amounts. with appropriate end-points to prove the benefits should be Two possibly conflicting trends are emerging for planned. Examples of relevant end-points are better choice molecular imaging diagnostic applications: of treatment and/or improved patient outcome due to & stricter rules for the approval of drugs and more information provided by new imaging techniques. expensive clinical trials There are, however, some important challenges & more contrast agents and tracers tailored to specific use connected to the adoption of strict rules for evidence-based and/or small subpopulations of patients medicine in medical imaging. Improvements are often incremental with a more or less continuous process of There is the risk that many promising methods with huge technology improvement and new applications. And when potential benefit for improved patient outcome will never there are cases of significant improvements, it has often be translated into clinical practice because the potential been argued that the benefit of the technology is self- market is too small to cover the costs of development. evident and that study designs with randomisation of patients to new and old technology is unethical. Industry Lack of Money and Resources as the Limiting Factor should be requested to prove, prior to marketing, that new for Medical Progress expensive technology is of added value to patient care. It is of importance for clinical research in general and for A challenge for the future healthcare system is that lack of money and resources may become the limiting factor for the services offered to the population. One reason is the 3 More at: ftp://ftp.cordis.europa.eu/pub/esfri/docs/esfriroadmap- demography arising from the ageing population. Another report-26092006_en.pdf reason is the wide range of progress in medical research for 4 EATRIS – European Advanced Translational Research Infrastructure diagnosis and treatment that is often costly. This challenge in Medicine can only be met through the dual focus on improved patient
  • 6. 1754 Eur J Nucl Med Mol Imaging (2008) 35:1749–1757 outcome and cost-efficient solutions within healthcare A well-defined problem is the ionizing radiation in the case systems. of x-ray and nuclear medicine. There are also concerns Medical imaging may become an important contributor about potential hazards from magnetic resonance when to obtain this dual goal. Even if new imaging technology is moving to higher fields and from ultrasound when moving expensive it may contribute significantly to cost-efficiency to higher frequencies. Many of the advanced methods in a labour-intensive healthcare system if the new methods include injection of new molecular probes (contrast agents, lead to shorter hospital stays, less use of non-efficient tracers, nanopeptides) with potential toxicity, side-effects treatment (surgery, drugs and others), and less recurrence of and adverse events. Medical imaging research must also disease. Improved patient outcome will also have an impact be focused on reducing these hazards and finding the on the society through reductions in sick leave, disabilities best compromise between patient safety and potential and nursing expenses. benefits. Cost-efficiency can also be obtained through develop- This safety assessment issue should be pro-actively ment of advanced methods in medical imaging into user- addressed in collaboration between academies, health care friendly tools that can be applied also by non-expert users industry and national and EC competent authorities. at the initial point of care. Cost-efficiency for the healthcare system should be included as a separate end-point for imaging research, and researchers with competence in how to evaluate economic Recommendations measures should be included in the planning of clinical trials. The main recommendation is to: Medical Imaging as a Research Tool 1. Obtain more and better medical imaging research in Europe through: Medical imaging is an important research tool to obtain new knowledge about disease processes and treatment & improved European collaboration, in particular between targets. Funding of medical imaging research and infra- different universities, between imaging specialists and structures is also needed for this purpose. Imaging is a non- clinical doctors, and between different imaging modalities invasive and well-suited technique for longitudinal studies & establishment of interdisciplinary research groups of that provides quantitative measures of the disease process- sufficient size and with access to long-term funding es. Both in a preclinical and a clinical research setting there & improved collaboration between academia and industry is medical imaging technology (equipment, contrast agents where research goals are defined by academia etc.) that will probably never be developed into tools for routine clinical use on patients, but which still benefit This is important in order to obtain medical imaging patient care through the new biomedical knowledge research with the necessary size and with true interdiscipli- obtained. narity, and for research to be adequately focused on the dual Medical imaging also has an important role to play in the goal of improved patient outcome and cost-efficient health- context of better and less expensive clinical trials for new care for the sake of improving European citizens’ health, drugs and therapies. Imaging may contribute in several better societies in Europe and improved competitiveness of ways: European medical industry. Other important recommendations are to: & better inclusion/exclusion of patients & better subgrouping of patients 2. Obtain more evidence-based medicine at European & imaging biomarkers may be used as a surrogate level through: outcome measure for the biological behaviour of & health technology evaluation different diseases & validations of standard clinical practice for optimal use The importance of this is underlined by the acquisition of imaging of large imaging R&D centres by the pharmaceutical & socio-economic measure of these new health technologies industry. 3. Establish appropriate education/training for widespread translation of new technology into new clinical practice. Safety Issues 4. Develop advanced methods within medical imaging The different imaging modalities present a wide spectre of into user-friendly tools that can be applied also by non- potential hazards for the patients and for the environment. expert users at the initial point of care.
  • 7. Eur J Nucl Med Mol Imaging (2008) 35:1749–1757 1755 5. Plan and fund both short- and long-term research Example 2 (early detection of subclinical disease) activities: There is exciting research activity with the combination of & short-term applied research is necessary for translation PET and functional MRI for the early diagnosis of of established new technology into new clinical practice neurodegenerative diseases, with a main focus on Alz- & long-term basic research is necessary to develop and heimer’s disease. There are now PET tracers that are evaluate new advanced methods, especially in the areas promising for noninvasive detection of Alzheimer plaques, of functional and molecular imaging, and to use medical and functional MRI may detect changes in functional brain imaging as a research tool to obtain new knowledge activity. For an optimal strategy for halting and/or postpon- about disease processes and new innovative therapies ing the development of dementia using cognitive enhancing drugs, mental training and others, it is of great importance Appendix to detect the early changes in functional brain activity due to disease progression. Some examples of promising new possibilities in medical imaging To show the wide variety of the possible roles for medical imaging, a few examples of new, promising methods and applications are presented. Example 1 (screening/risk factors/prevention) Several imaging techniques are promising for the character- isation of atherosclerotic plaques. A main target is to Fig. 5 Radiation treatment planning (right) of head/neck cancer based establish imaging biomarkers for vulnerable plaques and to on fusion of morphologic and functional information obtained with PET-CT (left) (courtesy of Prof. Liselotte Højgaard) be able to find the patients that have increased risk of plaque- induced myocardial infarction and thrombo-embolic stroke. New imaging techniques and molecular imaging probes in Example 3 (decision support for choice of treatment/ PET, MRI and ultrasound may detect inflammatory and personalised medicine) other biological processes in the plaques, and may be developed into a clinical tool for risk assessment of plaque CT, MRI and PET-guided images are used to target vulnerability. Plaque imaging may also be developed into radiation therapy toward the cancer and avoid harmful tools for monitoring the effect of preventive measures to radiation to healthy tissue (Fig. 5). reduce the plaque burden and/or the development into Diagnostic imaging tests could be of great value in the vulnerable plaques as shown in Fig. 4. This may both show selection of highly expensive treatment procedures: for the effect of life-style measures as well as drug therapy. example, new implantable pacemakers and arrhythmia defib- rillators with great potential in the therapy of heart failure have high costs and only a certain subgroup of patients would benefit from this therapy. New imaging techniques such as advanced ultrasound techniques, imaging of cardiac innerva- tion and metabolism may enable the identification of this subgroup of patients that will have an improved prognosis when using this expensive form of therapy. Example 4 (theranostics) Theranostics is a word to describe combined drug therapy and diagnostics5, and is the ultimate concept in targeted Fig. 4 Coronary artery imaging with multidetector CT and post- 5 processing characterisation of coronary plaques (courtesy of Prof. See ESF Forward Look on Nanomedicine at : http://www.esf.org/ Gabriel P. Krestin) fileadmin/be_user/research_areas/emrc/Nanomedicine.pdf
  • 8. 1756 Eur J Nucl Med Mol Imaging (2008) 35:1749–1757 drug delivery. A molecule targeted for the disease tissue As an example, in neurosurgery it is important for the (e.g. cancer) is linked both to a nonactivated therapeutic surgeon to avoid damage to the brain structures that will cause drug and an imaging contrast agent (tracer). In the case of dramatic functional deficits (limb paralysis, language func- ultrasound, the drug may be encapsulated in a gas bubble tion, visual etc.). An integrated protocol of new MRI methods and after injection the same ultrasound imaging equipment may, prior to the surgery, delineate important functional areas may be used first to ensure the correct localisation of the in the brain and their vital nerve fibre connections. This is of drug and then activate the drug through bursting of the great help to the neurosurgeon in the planning of the bubble with ultrasound waves. operation, and can also be displayed for the neurosurgeon in the operating theatre and updated during the surgical Example 5 (image guidance of stem cell therapy) intervention (tumour resection etc.), using image-guided minimal-invasive surgery with either MRI or ultrasound. Image guidance may be applied to stem cell therapy on Ultimately, further development of robotic imageguided many levels. First guidance of the delivery and placement surgery will provide computer assisted tools to facilitate of the stem cells, then tracking of any migration of labelled and increase safety of complex surgical procedures in all stem cells, then monitoring of the cell differentiation for the fields of surgery. target organ, and with functional imaging methods, moni- toring of improved organ function. Imaging techniques that Example 8 (patient follow-up) could be used for tracking stem cells in human include MRI, Nuclear Medicine (PET and SPECT) and possibly Cardiac ultrasound has reached a level where the myocar- ultrasound. dial wall function can be quantified and 3D visualised. Advanced ultrasound equipment is currently the size of a Example 6 (monitoring of drug therapy) portable computer and with ongoing research it may reach the size of a cell phone. With further development in the New imaging methods from PET and MRI produce user-friendliness of the advanced methods, it may be biological information on the growth potential of malignant tumours. This may be applied to noninvasive monitoring of the treatment effects of cytostatic drug therapy (usually a combination of several drugs). FDG-PET 6 can show a decrease in glucose uptake and different MRI methods can show reduction in angiogenetic potential. In a case of poor response, the treatment may be discontinued early on with a change to other drugs or to other therapeutic methods such as surgery or radiotherapy. Through this improved managed care the patient will get fewer adverse reactions, no ineffective therapy while it will lead to cost savings for the healthcare system. Example 7 (image-guided surgery) Imaging techniques can assist the surgeon both before and during surgery. Before surgery, image processing tools can provide realistic previews of the surgical field and of access pathways, with an interactive 3D anatomic display for appropriate planning. During surgery, image guiding can be valuable for target localization and detection of boundaries allowing, for instance, more complete and accurate resection of tumours, limiting damage to normal tissues. Fig. 6 Doppler ultrasound image (top) of metacarpophalangeal joints 6 PET scanning with the tracer fluorine-18 (F-18) fluorodeoxyglucose showing active inflammation (sinovitis). Corresponding MRI study (FDG) (bottom) (courtesy of Prof. Paul Emery)
  • 9. Eur J Nucl Med Mol Imaging (2008) 35:1749–1757 1757 possible for patients using multidrug therapy in heart failure Liselotte Højgaard, Clinic of Clinical Physiology, to have frequent follow-ups with an adjustment of dose, Nuclear Medicine & PET, University of Copenhagen, based on ultrasound image quantification of heart function, Rigshospitalet, Copenhagen, Denmark at the general practitioner’s office. Juhani Knuuti, Turku PET Centre, Turku University Likewise as shown in Fig. 6 below, combined morpho- Hospital, Turku, Finland functional imaging approaches (Doppler ultrasound and Gabriel P. Krestin, Erasmus MC, Department of Radiology, MRI with conventional and dedicated equipment) can be Rotterdam, The Netherlands used for the staged detection of disease activities and for Christiane Kuhl, Radiologische Klinik der Universität changes over time in rheumatic diseases, with potential Bonn, Bonn, Germany beneficial effects for health expenditures. George Laking, Christie Hospital NHS Trust, Manchester, United Kingdom Henrik Larsson, Functional & Diagnostic MR Unit, Experts Group on Medical Imaging for Improved Glostrup University Hospital, Copenhagen, Denmark Patient Care Borut Marincek, European Society of Radiology (ESR), Department of Medical Radiology, University Hospital Chairs Zürich, Zürich, Switzerland Chrit Moonen, CNRS, Laboratory for Molecular and Arturo Brunetti (Chair), CNR Institute of Biostructure and Functional Imaging, University Victor Segalen, Bordeaux, Biomages, Faculty of Medicine,Medical School, University France of Naples Federico II, Naples, Italy Hans Olav Myhre, Norwegian University of Science and Olav Haraldseth (Chair), MR Centre, Department of Technology, Trondheim, Norway Circulation & Medical Imaging, Faculty of Medicine, Gabor Rudas, MR Research Centre, Semmelweis Norwegian University of Science and Technology, University, Budapest, Hungary Trondheim, Norway Jordi Ruscalleda Nadal, European Society of Neurora- diology (ESNR), Servicio de Radiologia-Neuroradiologia, Scientific Experts Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Markus Schwaiger, TU Klinikum rechts der Isar, Silvio Aime, Dpto di Chimica Inorganica, Chimica Fisica e Medizinische Klinik München, Munich, Germany Chimica dei Materiali, Facoltà di Scienze M.F.N., Università George Sutherland, Department of Cardiological Sciences, degli studi di Torino, Torino, Italy St. George’s Hospital, London, United Kingdom Paolo G. Camici, MRC Clinical Sciences Centre, Imperial College London, United Kingdom EU Adviser Alberto Cuocolo, European Association of Nuclear Medicine (EANM), Department of Biomorphological and Tone Woie Alstadheim, Norwegian University of Science Functional Sciences, University of Naples Federico II, and Technology, Faculty of Medicine, Trondheim, Norway Naples, Italy Sturla Eik-Nes, National Center for Foetal Medicine, ESF-EMRC Department of Gynecology and Obstetrics, University Hospital of Trondheim, Trondheim, Norway Liselotte Højgaard, Chair of EMRC Carole Moquin-Pattey, Paul Emery, Academic Section of Musculoskeletal Head of Unit Thomas Bruhn, Science Officer Gwenaelle Le Disease, Chapel Allerton Hospital, Leeds, United Kingdom Cochennec, Administrator