Academic Center for Molecular and Cellular Imaging

Last updated: 321 days ago.

Molecular and Cellular Imaging (MCI) provides direct visualization and quantification of structure and function within living cells and organisms, in a non-invasive manner. With this knowledge, fundamental molecular mechanisms of disease are revealed, making MCI vital for understanding disease processes, for developing new diagnostic methods and novel drugs, and for evaluating treatment efficacy in a wide range of biomedical fields. The mission of this ACE is to develop, apply, and integrate imaging technologies to unravel disease pathways, and to translate new molecular probes to the clinic that will facilitate early detection of disease and theranostics. This ACE combines some of the most advanced expertise and knowledge in the world with top-notch imaging facilities to form a single entity that spans medical imaging from molecules to patients to populations.

Academic Center of Excellence

Research Activities

A main challenge of biomedical research in the postgenomic era is to unravel the molecular and cellular mechanisms of life. This ACE brings together researchers from a variety of disciplines and different levels (fundamental, translational, clinical as well as epidemiological) who develop, evaluate, and/or apply molecular and cellular imaging techniques within the context of fundamental, translational, and/or clinical questions.

The globally-recognized expertise of the scientists in this ACE, the multitude of advanced (pre-)clinical models, and the sophisticated and state-of-the-art imaging equipment and technologies that we have developed and validated combine to offer a unique platform for application across a broad stratum of diseases. The Optical Imaging Center (OIC), Applied Molecular Imaging Erasmus MC (AMIE), Scanning Force Microscopy (SFM), imaging of bio-nanomachines, and our wide-range of clinical molecular imaging platforms offer a one-of-a-kind combination of expertise and instruments. The Biomedical Imaging Group Rotterdam (BIGR) provides cutting edge image analysis applications and developments in this ACE.

Fundamental: Imaging techniques are being developed or used to unravel disease mechanisms through which novel, specific targets / potential biomarkers for diagnostic imaging or treatment can be defined.

Translational: Research uses imaging, including MRI, PET, SPECT, optical imaging, scanning force microscopy, and sonography, as well as in vitro and in vivo models to design, synthesize and evaluate new biomarkers, imaging probes, drugs, drug delivery systems, and treatment strategies for their potential for clinical translation. Application areas include oncology, cardiovascular disease, neurological disorders, and musculoskeletal disorders.

Clinical: Clinical evaluation, validation and application of new imaging biomarkers, imaging probes, drugs and treatment strategies in a variety of clinical fields such as oncology, neurology, cardiovascular disease and musculoskeletal disorders.

Epidemiological: The purpose of the population-based Rotterdam Study and the Generation R study is to elucidate determinants, including genetics, of common musculoskeletal diseases such as osteoarthritis, and of normal versus abnormal musculoskeletal development and health.

Type of

Collaborations

International: Stanford University, EPFL Lausanne, EORTC, UCL London, Fels Institute for Cancer Research Philadelphia, MSK cancer center New York, University of Iowa USA.

National: Delft University, VU Amsterdam

Other ACE's: Bone and Joint, Spine, Systems Biology, Genome Repair Targeted Cancer Treatment, and Aneurysms

Within the ACE: Essers/Meijerink, funded TKI-LSH grant application ‘Quantitative in vivo imaging of heart failure; Development of in vivo models for research use, drug discovery and drug development

Within the ACE: Essers/Lowik, funded NWO apparatuuraanvraag 2017: In Vivo Optoacoustic Molecular Imaging for applied cancer, aging and cardiovascular research

Within the ACE: Wyman/Houtsmuller, expanding super resolution of nuclear structures in DNA repair and cancer avoidance

Within the ACE: Wyman/Houtsmuller, applications of machine learning to advance analysis of DNA repair proteins by single particle tracking, response to DNA damage and repair process

Educational

Contributions

Clinical education:

  • Bachelor program Clinical Technology (Medical Delta), a multidisciplinary study program to integrate technological expertise with medical understanding
  • In the new Master program in Clinical Technology - Bachelor program Medical Imaging and Radiation Therapy (MBRT), training of radiographers

Medical Curriculum (Erasmus MC) at both Bachelor- and Master-level

  • Master program Technical Medicine - Resident (AIOS) education for the specialization Radiology (including Nuclear Medicine) - International/European clinical education, including the European Course of Neuroradiology and the European School of MRI Research Education: - Bachelor program NanoBiology (TU-Delft, Erasmus-MC, Medical Delta)
  • Master programs and PhD education within the MolMed, I&I, COEUR, MGC, ONWAR, NIHES, and ASCI research schools - International course "Microscopic Image Analysis"

level Master/Doctorate/Post-doc

  • Doctorate education: combined number of PhD Students in all groups is ±50
  • ACE members organize and participate in post-doctoral education in the form of symposia, courses, hands-on workshops etc., on a local (Erasmus MC), national, and international level - World-renowned AMIE Translation Imaging Workshop

level Doctorate/Post-doc

  • PhD/Postdoc education program of the Optical Imaging Center (www.erasmusmc.nl/oic)
  • Laboratory Animal Science qualification course (Imaging methods for small animals)
  • European Association of Nuclear Medicine Track on Basic and Translational Research in Molecular Imaging and Therapy: "From Molecule to Man"
  • The PIs are active in their respective (international) professional societies and the associated educational programs (clinical and pre-clinical)

Patient

Care Activities

State-of-the-art imaging equipment and imaging tools (tracers) along with a high level of subspecialized expertise is leveraged to provide high-end clinical care, including diagnosis and treatment (theranostics) of rare and complex disorders typical for a tertiary referral center. We participate actively in multidisciplinary patient conferences and provide expert consultations on a regional and national level.

There is a recent trend in Radiology towards more functional and molecular imaging as an adjunct to traditional anatomical imaging. Reflecting the excellent standard of care in our center, a number of these novel techniques have already been implemented for routine clinical care or are being evaluated in large-scale clinical trials embedded in routine patient care. For example, in neuroradiology, functional MRI of the brain is an essential part of the pre-operative work-up of patients with brain tumors, as it offers critical information on brain signal pathways in addition to the more traditional morphological images. In neuro- & musculoskeletal, prostate, cardiac, neuroendocrine diseases, specialized MRI sequences or SPECT and PET imaging offer information about cellular and tissue characteristics.

These are now used in clinical practice to help identify specific pathologies such as stroke, tumors, and infection. In these fields of clinical radiology and nuclear medicine, the complementary information of anatomical and functional imaging is also reflected in a rapid increase in the use of hybrid morphological and nuclear imaging techniques, such as PET- and SPECT-CT. A new PET-MRI scanner will be available in 2019 which will enable enhanced characterization and monitoring of a variety of diseases, in particular in the field of oncology.

Societal Relevance to Research, Education and Patient Care

As molecular and cellular imaging (MCI) provides a direct visualization of normal physiology and disease processes, this ACE deepens our knowledge for and contributes directly to the fundamental shift of precision diagnostics in medical care and research. Accurate patient stratification and response assessment at the molecular level is not only relevant for currently available treatments, but also for therapeutic trials that require intensive follow-up, preferably at low cost, high precision and non-invasively.

Members from this ACE are in close association with international organizations such as the European Organization for Research and Therapy in Cancer (EORTC) and thus for instance uniquely situated to implement such techniques directly at the European level and at the forefront of cancer research and translation to patient care. Similar contributions can be seen at the more fundamental level, where animal models can be imaged in vivo, and where developed techniques are patented.

The 2016 revision of the WHO classification for brain tumors is one example of the important role of molecular information and how it is already finding its way into – diagnostic – guidelines, with care standards to follow. MCI provides the opportunity to obtain such molecular information more cost-effectively than through costly and not universally accessible diagnostic procedures (e.g. sequencing panels). Continued education on MCI is provided through MolMed, as well as the clinical training programs at the BSc, MSc and MD level, through lectures/workshops as well as research internships.

Viability of Research, Education and Patient Care

The ACE MCI is viable. We have a strong, stable core of personnel in permanent employment (of which 40% are female) providing continuation of expertise, knowledge, grants and publications into the future. The average age of our leading investigators is 52 years, ranging from 38 to 61 years.

Our publication record speaks for itself: since 1995, the PIs have authored at least 1934 scientific publications, which are cited around 6500 times a year. Various groups within the ACE have collaborated intensively for years and will continue these productive collaborations within the ACE.

We continously seek the opportunity for new collaborations within our ACE, with other ACE's in Erasmus MC, and with national and international partners are initiated. Furthermore, many of our senior researchers are actively involved in international societies, including global education in the field, and our clinical partners are often requested to give input for medical guidelines and consensus opinions. Given the importance of novel technologies in molecular imaging, we also maintain a network of industrial relations providing in-depth insight into upcoming technology.

Many members are intensively involved in research schools or Bachelor/Master programs. The ACE is multidisciplinary, including besides physicians of different specialisms, also physicists, computer scientists, biologists and chemists. An area of special focus in this ACE is the translation of expertise & knowledge developed in fundamental or pre-clinical research into clinical research programs, ensuring that our innovations benefit healthcare.

Key and relevant publications of the last five years

  • Hawinkels LJ, de Vinuesa AG, Paauwe M, Kruithof-de Julio M, Wiercinska E, Pardali E, Mezzanotte L, Keereweer S, Braumuller TM, Heijkants RC, Jonkers J, Löwik CW, Goumans MJ, Ten Hagen TL, Ten Dijke P. Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors. Clin Cancer Res 22:96-106 (2016)
  • Van Tiel J, Kotek G, Reijman M, Bos PK, Bron EE, Klein S, Nasserinejad K, Van Osch GJ, Verhaar JAN, Krestin GP, Weinans H, Oei EHG. Is T1ρ mapping an alternative to delayed gadolinium-enhanced MR imaging of cartilage in the assessment of sulphated glycosaminoglycan content in human osteoarthritic knees? An in vivo validation study. Radiology 279:523-31 (2016)
  • Das AM, Eggermont AM, ten Hagen TL. A ring barrier-based migration assay to assess cell migration in vitro. Nat Protoc 10:904-15 (2015)
  • Reuter, M., A. Zelensky, I. Smal, E. Meijering, W. A. van Cappellen, H.M. de Gruiter, G.J. van Belle, M.E. van Royen, A.B. Houtsmuller, J. Essers, R. Kanaar, C. Wyman. BRCA2 diffuses as oligomeric clusters with RAD51 and changes mobility after DNA damage in live cells, J Cell Biology 207:599-613 (2014)
  • De Jong M., Essers J., van Weerden W.M. Imaging preclinical tumour models: improving translational power. Nature Rev Cancer 14:481-493 (2014)
  • N. Chenouard, I. Smal, F. de Chaumont, M. Maška, I. F. Sbalzarini, Y. Gong, J. Cardinale, C. Carthel, S. Coraluppi, M. Winter, A. R. Cohen, W. J. Godinez, K. Rohr, Y. Kalaidzidis, L. Liang, J. Duncan, H. Shen, Y. Xu, K. E. G. Magnusson, J. Jaldén, H. M. Blau, P. Paul-Gilloteaux, P. Roudot, C. Kervrann, F. Waharte, J. Y. Tinevez, S. L. Shorte, J. Willemse, K. Celler, G. P. van Wezel, H. W. Dan, Y. S. Tsai, C. Ortiz de Solórzano, J. C. Olivo-Marin, E. Meijering. Objective Comparison of Particle Tracking Methods. Nature Methods 11:281-289 (2014)
  • Van den Bent M, Smits M, Kros HM, Chang S. Diffuse Infiltrating Oligodendroglioma and Astrocytoma. J Clin Oncol 2017 ;35:2394-2401.
  • Mezanotte L, van 't Root M, Karatas H, Goun E, Lowik C. In vivo molecular bioluminescence imaging: new tools and applications. Trends Biotechnol. 2017;35:640-652.
  • Baar MP, Brandt RMC, Putavet DA, Klein JDD, Derks KWJ, Bourgeois BRM, Stryeck S, Rijksen Y, van Willigenburg H, Feijtel DA, van der Pluijm I, Essers J, van Cappellen WA, van IJcken WF, Houtsmuller AB, Pothof J, de Bruin RWF, Madl T, Hoeijmakers JHJ, Campisi J, de Keizer PLJ. Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. 2017 Mar 23;169(1):132-147.e16.
  • Paul, M.W., Zelensky, A.N., Wyman, C. and Kanaar, R. (2018) Single-Molecule Dynamics and Localization of DNA Repair Proteins in Cells. Methods Enzymol. 2018;600:375-406.

PhD theses of the last five years

  • Ilya Skachkov (2016) Microbubbles for molecular imaging and drug delivery
  • Rebecca Steketee (2016) Advanced MR neuroimaging in early stage presenile dementia
  • Bert-Jaap van Belle (2015) Differential Pathway Control in Nucleotide Excision Repair
  • Jasper van Tiel (2015) Quantitative Imaging Biomarkers of Knee Cartilage
  • Bilyana Dicheva (2015) Targeted thermosenstive liposomes and mild hyperthermia for local drug delivery to tumors
  • Natasja Ramnath (2014) Molecular pathogenesis of Fibulin-4 associated aortic aneurysms
  • Tessa Brabander (2017) Imaging and Therapy of Neuroendocrine Tumors with radiolabeled somatostatin analogs
  • Bibi van Thiel (2017) Multimodality imaging of cardiovascular dysfunction; risk factors, diagnostics and treatment options
  • Rozanna Meijboom (2017) Imaging of brain connectivity in dementia: clinical implications for diagnosis of its underlying diseases
  • Simone Dalm (2017) The application of radiotracers for theranostic use in breast cancer

Non-scientific publications related to the ACE

  • Kwaliteitscriteria Neuro-oncologische zorg - Marion Smits
  • Richtlijn glioom 2013 - Marion Smits
  • KWF onderzoeker van de Week: Marion de Jong. Prostaatkanker beter behandelen met radionucliden.
  • E Meijering. From cells, to images, to numbers, reliably. mRNA 2(2):18-20, April 2017.
  • Richtlijn conservatieve behandeling van artrose 2018 – Edwin Oei
  • Imago 2018: "Kwantitatieve beeldvorming geeft radiologie ontbrekende maat en getal" – Edwin Oei

Principal coordinator(s)