Imaging
Discussion In Table 1 the product offerings of the 12 compa- nies discussed in this article are compared with respect to the imager modalities offered; whether or not they support multi-mode imaging on the same instrument or via co-registration; and the types of imaging reagents, tracers, contrasting agents and probes offered. Some trends were evi- dent from the vendor’s contributions: Compact systems: There seems to be increasing emphasis on building compact benchtop systems that can be placed anywhere in a research lab, which are not constrained by physical limitations eg those placed on traditional MRI systems due to their active magnetic fields. Reducing system complexity such that they can be operated by researchers with no prior imaging experience will further help to pro- mote accessibility, as will the anticipated availability of more cost-effective imaging solutions (Aspect Imaging, Carestream and Sofie). Multi-Modality: Animal imaging systems that sup- port bi- or even tri-modal combinations (on the same instrument) are on the increase, this is partic- ularly true for the PET, SPECT and CT modalities (Bioscan, Carestream, Siemens and Sofie). In con- trast, fixed instruments combinations of optical (fluorescence) imaging are mainly in combination with x-ray CT or micro CT (Bioscan, Caliper & Carestream). Most other optical imaging instru- ments are single modal and rely on co-registration with other imaging modes (MRI, CT and PET), based on the fiduciary marks on the imaging cas- sette that holds the test animal, to combine absolute functional quantification with precise anatomical localisation in vivo (Aspect, Berthold, Caliper, Carestream, LI-Cor, PerkinElmer and UVP). Higher Resolution: As new imaging systems incor- porate novel detectors, technologies, electronics, advanced software system modelling and recon- struction algorithms, we are seeing higher spatial resolution, unmatched sensitivity with no loss in the speed of acquisition, such that the specifica- tions of some animal imagers will soon exceed their clinical equivalents (Bioscan, Carestream, Siemens, Sofie, VisualSonics). Better Reagents: Imaging systems that utilise visible fluorescent probes typically have low target-to- background ratios and shallow tissue penetration due to high tissue autofluorescence and light scatter- ing at visible wavelengths. Excitation at near- infrared (NIR) wavelengths achieves high target-to- background ratios with deeper tissue penetration. With this in mind vendors (BioScan, Caliper, LI-Cor, Miltenyi Biotec, PerkinElmer and UVP) have devel- oped a broad range of fluorescent probes labelled in
Drug Discovery World Summer 2011
the red and NIR for use in single-target or multi-tar- get optical imaging of cells or organs in vivo. Bioluminescent biosensors are also proving very use- ful in imaging cell death in cancer cell lines and in the evaluation of preclinical efficacy in mouse mod- els (Promega). During in vivo imaging it is necessary to have contrast between the intensity of the signal and the background level, this is usually achieved using contrast agents. Several vendors are active in producing in vivo contrast agents for preclinical imaging in small animals using the modalities MRI, CT, optical imaging and ultrasound (Aspect, Bioscan, Miltenyi Biotec, Siemens and Sofie). Advanced Software: All imaging systems are heavily reliant on advanced software systems and algorithms for reconstruction of the 3D image and co-registration of multiple imaging modalities. Some vendors have implemented new software including latest image pro- cessing methods such as transparency, combined con- trast settings or image overlay (Berthold) and the abil- ity to define an intensity threshold distinguishing the signal and background based on their spectral charac- teristic and expected distribution (UVP). Translational Research: Facilitating translational research is emerging as the favoured way of market- ing in vivo preclinical imaging, with most vendors promoting this concept. In reality, this is nothing new. Bridging the gap between in vitro exploratory and in vivo clinical research has long been recognised as the niche where in vivo imaging plays best. What, how- ever, has changed is the small animal models of human disease or native cells used may now be more conducive to translational research, which when cou- pled with our ever increasing ability to track cellular or organ changes in vivo should allow better transla- tion of research findings to human clinical trials. In conclusion, the trends highlighted suggest the tools necessary to facilitate significant improve- ments in small animal imaging are now becoming mainstream and we should expect to see major advances in in vivo imaging as applied to transla- tional research over the coming years.
DDW
Dr John Comley is Managing Director of HTStec Limited, an independent market research consultan- cy whose focus is on assisting clients delivering novel enabling platform technologies (liquid handling, lab- oratory automation, detection instrumentation and assay reagent technologies) to drug discovery and the life sciences. Since its formation seven years ago, HTStec has published more than 50 market reports on enabling technologies and Dr Comley has authored more than 30 review articles in Drug Discovery World. Please contact
info@htstec.com for more information about HTStec reports.
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References 1 In Vivo Preclinical Imaging Trends 2011 Report, published by HTStec Limited, Cambridge, UK, January 2011. 2 Galbán, S et al (2011). Imaging caspase dependent cell death as a surrogate for efficacy of cancer therapeutics. AACR Annual Meeting, Abstract #:LB-334.
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