SBIR-STTR Award

Drug development and disease molecular research tend to rely on large numbers of animals which must be sacrificed in order to determine a compound's effects. This process is time consuming and costly. However, small animal imaging methods are non-invasive, enabling researchers to use the same animal repeatedly in longitudinal studies and reduce development time and costs. One important imaging modality is micro Computed Tomagraphy (CT). Micro-CT is capable of revealing exquisite anatomical detail with high spatial resolution in the mouse; this is important for evaluating phenotype changes that occur in genetically modified animals. Use of micro-CT is also valuable in evaluating tumor kinetics, i.e., growth or reduction with chemotherapy. We propose to develop a novel CT system for small-animal imaging which uses a photon-counting approach with x-ray energy-discrimination capabilities and simultaneous detection of all photon energies. Our technology is based on use of two-dimensional CdZnTe (CZT) detector pixel arrays flip-chip bonded directly to a readout integrated circuit (1C) chip with a matching channel array. Such an x-ray detection system comes at an excellent time when several companies are developing contrast agents for mouse investigators. The use of multiple energy detection suggests the possibility of multi contrast agent evaluation in an animal during a single CT scan. In Phase I, we will investigate the feasibility of this innovative concept through experiments using existing channel-array chips and CZT pixel detectors, studies of such within a test micro-CT platform and computer simulations for the future readout chip. We will also develop the requirements and preliminary design specifications for the new chip and CZT pixel array as well as the envisioned photon-counting micro-CT system. At the end of Phase I, feasibility will be demonstrated and a preliminary design of the detector system will be ready. In Phase II we plan to design, fabricate and test a new readout chip, mount it to a suitable detector array, and build detector modules for a micro-CT system. The imaging capabilities and performance of this instrument will be determined and characterized. Our proposed effort targets the development of a CT system for small-animal imaging as a tool for drug discovery and disease research. It can however be adapted to diagnostic imaging of humans or to industrial imaging, thus greatly enhancing both the public benefits and commercial potential of the proposed project

The global small-animal/molecular in-vivo imaging market is vast and growing as more pharmaceutical companies and academic institutions realize the scientific and economic benefits of incorporating this approach in disease and drug development research. In the U.S., the preclinical imaging market has transitioned from an emerging market in 2002 to an established one today. American manufacturers presently project the cost of developing a new pharmaceutical to be as high as $300 million for each released drug with an average 12-year development time. In the currently used method of histopathology, a large number of animals are sacrificed to obtain samples for evaluation at different points in time. On the other hand, small animal imaging involves non- invasive imaging techniques that enable molecular targets and genetic processes to be visualized and measured in living laboratory animals. The various imaging modalities (optical, magnetic-resonance, x-ray, nuclear) allow researchers to use the same animal repeatedly thus dramatically reducing overall costs. Small animal imaging manufacturers are unencumbered by the regulatory approval process that is required for clinical diagnostic and therapeutic imaging equipment. This favors rapid commercialization of breakthrough imaging products which should accelerate drug discovery and help make medicinal cures more affordable. We propose to develop a novel computed tomography (CT) system for small-animal imaging. The proposed micro-CT system will use a photon-counting approach to achieve multi-energy imaging capability that will overcome many of the limitations of current dual-energy CT systems. Improvements over those systems will include significantly better energy resolution, more energy levels, flexibility in the selection of the energy ranges, and simultaneous detection of all photon energies in the same detector volume. This last item eliminates problems related to registration of the images that can be a concern in the traditional dual-kVp or dual-detector approaches to dual-energy CT. Our Phase I study demonstrated the feasibility of the proposed small-animal CT detector. During this study we clearly defined our detector concept, tested precursor pixel detector readout devices, prepared preliminary specifications and performed initial design work and circuit simulations. We also reviewed/refined the overall system requirements for small-animal CT with our academic and industrial consultants. Moreover, we investigated various options for detector supply, processing and assembly to ensure Phase II project success and Phase III product viability. During Phase II we plan to develop the components for the CT detector devices and then assemble and characterize their performance under small-animal imaging conditions. The prototype detectors will be evaluated at NOVA and leading academic and industrial laboratories. We likewise plan to develop a prototype small-animal CT system to make larger images (e.g., of phantoms). During Phase III we will seek funding for preclinical trials and pursue commercialization with our industrial collaborators.

Public Health Relevance:
Our proposed small-animal CT system would provide both anatomical and functional information within a single imaging modality as enabled by breakthrough multi-energy x-ray detector technology and innovative contrast agents. An important niche application would be that of advanced studies of soft-tissue structures, processes and disease mechanisms based on animal models. These areas of research are growing with the demand for new therapeutic approaches against heart failure, colorectal cancer and osteoarthritis.

Public Health Relevance:
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