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What are the most valuable synergies between biological microscopy, research in vivo imaging, and medical imaging?


- Lucy Collinson, Tony Ng, Martyn Chamberlain, Tony Gee, Jemima Burden, Dave Clarke, Boris Vojnovic, Jeremy Skepper


1) Connectivity Workgroup Roundtable Discussion, September 2010

An informal Connectivity Workgroup Roundtable Discussion was held on Tuesday 14th September 2010 at the Cancer Research UK London Research Institute. Attendees included Lucy Collinson (Electron Microscopy, CRUK LRI), Anton Page (Biomedical Imaging Unit, Southampton General Hospital), Martyn Chamberlain (Biophysical Sciences Institute, Durham University), Chris Phillips (IR imaging, Physics, Imperial College), Jason Swedlow (BioImagingUK and WT Centre for Gene Regulation and Expression, Dundee University), Jemima Burden (Electron Microscopy, MRC Laboratory for Molecular Cell Biology), Tony Ng (Cell and Molecular Biophysics, Kings College), Liz Duke (Diamond Synchrotron), Raffa Carzaniga (Electron Microscopy, Imperial College), Tony Gee (PET and Tracer Development, Kings College), Dave Clarke (STFC, Rutherford Appleton Lab), Jeremy Skepper (Cambridge University) and Boris Vojnovic (Advanced Technology Development Group, Oxford University).


No single imaging technique is capable of analysing structure across scales from 'patient-to-protein'. Our ultimate goal is an analysis that, for example, would identify a tumour in a patient, image the cellular and subcellular changes within the tumour, and assess the targeting and efficacy of therapeutic agents. A critical part of this ambitious goal is the linking of multiple imaging modalities to analyse structure across scales, from whole organisms to tissue microanatomy to subcellular ultrastructure to macromolecular localization in a single sample. This would involve connecting equipment and expertise across a variety of biomedical imaging fields. The BioImagingUK community is well placed to make the necessary connections to undertake such a large scale project.

What are the most valuable synergies between biological microscopy, research in vivo imaging, and medical imaging?

Synergies already exist between different imaging modalities. Correlative light & electron microscopy (CLEM), correlative light and X-ray microscopy, and correlative light & MRI are examples of multimodal imaging techniques that are currently being applied to important biological questions. In addition, commercial systems that combine imaging modalities within a single instrument are coming onto the market (eg fluorescence and electron microscopy, PET and MRI). In human patients, intraoperative tumor-specific fluorescence imaging has showcased potential biomedical applications for imaging techniques originating from the research laboratory (van Dam et al, Nature Medicine, 2011). We aim not only to define possible synergies, but to identify and enable those that leverage existing and growing expertise within the BioImagingUK community. Initially, we will gather a list of established imaging technologies, a list of publications on correlative imaging in order to define existing expertise, and a list of imaging probes so that we can begin to consider how to use or adapt markers for multimodal imaging. Our aim is also to identify important scientific questions that can only be answered by imaging across scales in the same sample (ie patient-to-protein). Proposals to develop, acquire and/ or connect imaging equipment, probes, software and expertise would then be assembled, based on specific applications in biological discovery and disease.

What do we require to make these synergies happen?


• Within the imaging community to create a snapshot of what biomedical imaging currently encompasses

• Between basic research and clinicians (giving medics the tools eg imaging through an endoscope)

• With industry to push development of tools required to answer the big questions

• Between biologists, clinicians, chemists, physicists, mathematicians, modellers, image analysts, engineers...


• Access to (often expensive) imaging tools

• Assessment of co-location of imaging equipment and expertise at each tier from small to medium to large scale facilities

• Physics engineering for modification of existing imaging tools and development of new integrated multi-modal imaging tools


• Development of markers that can be detected across imaging modalities and across scales (chemistry, physics, imaging)

• Probes which are fit for human use. This needs a community approach to develop and test for biophysical charaterisation, specificity, selectivity, toxicology, metabolic stability, validation etc etc (medicinal chemistry, pharmacology)

• Creation of a virtual centre for probe development

• Label-free imaging eg IR in cancer research (use multiple imaging techniques for validation?)

Sample preparation

• Optimisation of protocols for imaging a single sample in different imaging platforms

• Assessment of artefacts induced by removing samples from a patient? Can we take imaging techniques and put them into the patient instead?

• Imaging samples as close to ‘native state’ as possible

Software, Maths, Modelling

• Software for correlating datasets from different imaging modalities

• Consult other communities who already work with multiple imaging platforms across scales eg astronomy, metrology


• Courses covering multiple imaging disciplines, emphasising wherever possible the commonalities and overlap between different imaging modalities

• One year training courses for clinicians in multiple imaging techniques (requires the offer of training sites from the imaging community and sponsorship to cover costs at these sites)


Gather information from the BioImagingUK community

• Gather a comprehensive list of imaging techniques, standard and novel

• Gather a list of probes (particularly those with multiple contrast mechanisms e.g. USPIO's that are MRI contrast agents and are electron dense) and a list of label-free techniques used in all imaging modalities

• Gather a list of key publications on correlative imaging published by the BioImagingUK community

Organise meetings

• Organise a one day symposium to bring together experts in all aspects of correlative imaging. Format suggestions include food and wine/ speed dating/ lightening talks

• Approach RMS about organising a series of lectures on different aspects of biomedical imaging

• Set up a forum to bring together experts in sample preparation for different imaging techniques

2) Connectivity Workgroup Discussion at the 4th Facility Managers Meeting, January 2011

A small breakout session discussed how to implement the action points from the September meeting [[1]]. Attendees included Lucy Collinson (Cancer Research UK London Research Institute, EM Unit (Chair)), Peter March (Manchester University, BioImaging Facility), Sam Swift (Dundee University, CHIPS and LMF) and Tim Self (Nottingham University).


Connectivity encompasses three main areas:

1) Connecting people and expertise across the UK BioImaging community.

2) Facilitating access to equipment across the UK BioImaging community.

3) Connecting equipment and expertise to enable ‘Patient-to-Protein’ imaging across scales.

The meeting began with an overview of previous Connectivity Workgroup discussions. The aim of this breakout session was to work out how to progress the following action points:

1) Gather a comprehensive list of imaging techniques, standard and novel.

2) Gather a list of probes (particularly those with multiple contrast mechanisms e.g. USPIO's that are MRI contrast agents and are electron dense) and a list of label-free techniques used in all imaging modalities.

3) Gather a list of key publications on correlative imaging.

4) Organise a one day symposium to bring together experts in all aspects of correlative imaging. Format suggestions include food and wine/ speed dating/ lightening talks.

5) Approach RMS about organising a series of lectures on different aspects of biomedical imaging.


The creation of a virtual microscopy network could start to address many of the above action points. This could be achieved by setting up a BioImagingUK website which would host a range of information and facilitate connectivity within the UK community. Experts in each field could contribute to the site. The website content could include...

• A comprehensive list of Bioimaging techniques.

• A list of probes used in different imaging modalities, highlighting those that can be detected in multiple imaging modalities for correlative microscopy. Entries could include comments and an Amazon-style ‘star’ rating for experienced users to rate the use of probes on different samples.

• A link to the list of UK Biological Imaging Facilities hosted by the University of York.

• ‘How-to’ movies made by the community, starting with light microscopy and electron microscopy and expanding to include biolmedical imaging. This could include sample preparation tips and tricks, maintenance and alignment of equipment, use of imaging platforms and image analysis tools. There could also be a collection of links to commercial instructional movies. For minor individual effort there would be a large return for the whole imaging community.

• A central repository for protocols.

• A list of facilities willing and able to host one-to-one training in sample preparation, imaging and/ or image analysis. Funding may be required to allow facilities to host training. It may also be of benefit for the training to be recognised as individual modules in an overall imaging qualification, which may help facilities justify the time spent training and learning.

• A list of upcoming talks and meetings with links to live broadcasts and webinars.

• An online forum for connecting biologists and imaging technologists with chemists, mathematicians, image analysts, physicists, engineers etc for problem solving and development.

• Industry could be involved by providing sponsorship for the web page in return for links to their websites and by contributing links to training videos.

• A list of community-owned equipment which could be loaned for short periods of time. This would require agreement from the funding bodies and manufacturers in terms of insurance/ coverage by service contracts for moving equipment.

Other discussions included...

• The use of PhD CASE studentships for development of imaging technology.

• Opening the facility managers meeting to any community where images are the readout.

• Research councils having a central repository of imaging equipment which can be loaned out, particularly for live cell imaging.


• SS to provide a figure showing the different imaging modalities as a seed for information.

• LC to look into funding for a web programmer to set up a BioImagingUK website with downloadable documents, videos, profiles, training etc., to be coordinated with Jason Swedlow.

• LC, SS and PM to trial VIVO for online conferencing with multiple people. Could be useful for hosting small, regular workgroup meetings.

• Community to submit training videos to LC. A list of those contributing and their chosen topics will be updated below, prior to the creation of the website. Please encourage your colleagues to contribute. A ‘one take’ policy may be useful! If you have any advice on movie-making please submit this to LC for inclusion below. Useful links for videos include the Molecular Expressions website, Media Cybernetics training videos (James Francis), Camtasia software for recording desktops.

• Current Facility Managers Meeting invitees to pass on information to other imaging communities, who should register their interest, to be included in the emails for next year’s meeting.


  • Your help is needed - please email with suggestions
List of imaging techniques and current synergies
List of imaging probes

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Duer MJ et al. 2008. Mineral surface in calcified plaque is like that of bone. Arteriosclerosis, Thrombosis, and Vascular Biology. 28:2030 [3]

Hegyi L et al. 2004. Short term arterial remodelling in the aortae of cholesterol fed New Zealand white rabbits shown in vivo by high-resolution magnetic resonance imaging - implications for human pathology. Pathology Oncology Research. 10: 159-165 [4]

Menon DK et al. 2004. Diffusion limited oxygen delivery following head injury. Crit Care Med. 32:1384. [5]

Mueller K et al. 2007. Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro. Biomaterials. 28:1629-42 [6]

Olsen ES et al. 2010. Activatable cell penetrating peptides linked to nanoparticles as dual probes for in vivo fluorescence and MR imaging of proteases. PNAS. 107:4311-6 [7]

Trivedi RA et al. 2004. In vivo detection of macrophages in human carotid atheroma: temporal dependence of ultrasmall superparamagnetic particles of iron oxide-enhanced MRI. Stroke. 35:1631-5 [8]

Young VE et al. 2010. Diffusion-weighted magnetic resonance imaging for the detection of lipid-rich necrotic core in carotid atheroma in vivo. Neuroradiology. 52: 929-36 [9]

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