Connectivity
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What are the most valuable synergies between biological microscopy, research in vivo imaging, and medical imaging?
Members
- Lucy Collinson, Tony Ng, Martyn Chamberlain, Tony Gee, Jemima Burden, Dave Clarke, Boris Vojnovic, Jeremy Skepper
Activities
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).
Background
No single imaging technique is capable of analysing structure across scales from 'patient-to-protein'. This type of analysis would allow us to (for example) identify a tumour in a patient, image the cellular and subcellular changes within the tumour, and assess the targeting and efficacy of therapeutic agents. We may be able to achieve this ambitious goal by linking multiple imaging modalities to analyse structure across scales, from whole organisms to tissue microanatomy to subcellular ultrastructure and protein 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) and correlative light & MRI are examples of multimodal imaging techniques that are currently being applied to important biological questions. In addition, commercial systems which combine imaging modalities within a single instrument are coming onto the market (eg PET and MRI, fluorescence and electron microscopy). However, to fully answer this question we need to gather information from the BioImagingUK community. Initially, we would like to gather a list of imaging techniques across the spectrum, a list of publications on correlative imaging so that we can start to identify hotspots of 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 which can only be answered by imaging across scales in the same sample (ie patient-to-protein). Grant applications to acquire and/ or connect imaging equipment, probes, software and expertise could then be assembled. This effort will drive APPLICATION focused development rather then ‘technology for technology’s sake’.
What do we require to make these synergies happen?
Communication
• 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 question
• With chemists, physicists, mathematicians, modellers, image analysts, engineers...
Equipment
• 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
Probes
• 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
Training
• Courses which cover multiple imaging disciplines
• 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)
Actions
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
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
Resources
- Your help is needed - please email lucy.collinson@cancer.org.uk with suggestions
List of imaging techniques and current synergies
List of imaging probes
Publications
Armer HEJ et al. 2009. Imaging transient blood vessel fusion events in zebrafish by correlative volume electron microscopy. PLoS ONE. 4:e7716 [1]
Duer MJ et al. 2008. Mineral surface in calcified plaque is like that of bone. Arteriosclerosis, Thrombosis, and Vascular Biology. 28:2030 [2]
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 [3]
Menon DK et al. 2004. Diffusion limited oxygen delivery following head injury. Crit Care Med. 32:1384. [4]
Mueller K et al. 2007. Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro. Biomaterials. 28:1629-42 [5]
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 [6]
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 [7]
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 [8]
