Preclinical animal models are used extensively in cancer research to evaluate drug efficacy and toxicity and to better understand the disease's complex fundamental underlying processes. In vivo imaging studies enable researchers to longitudinally assess tumor presence, functional status, and response the therapy without the need to sacrifice animals for each read point. Anatomical imaging modalities (MRI, CT, and Ultrasound) enable the visualization and assessment of tissue structures, which are necessary to localize the signals acquired via the molecular imaging modalities (PET, SPECT, and Optical), which assess the functional status of tissues (tumor metabolic demand, molecular signal expression, drug biodistribution, etc.). Ultrasound is the least expensive of the anatomical modalities with the fastest acquisition time, but there is no ultrasound product on the market for whole body imaging, thus researchers often resort to MR or CT based anatomical imaging for their dual modality studies. MR and CT imaging studies are slow, expensive, and reduce study throughput. We propose to build a high throughput and low cost ultrasound-optical hybrid modality system which could speed up preclinical drug research, as well as drive down costs. Our company, SonoVol, is the result of several years of strong collaborative academic-industry research between Dr. Paul Dayton's ultrasound imaging lab at UNC and Dr. Stephen Aylward's image analysis lab at Kitware. Unlike MR or CT, our SonoVol device is an inexpensive and benchtop imaging system which can capture a whole body mouse image in less than 5 minutes. We are proposing to build the after- market hardware and software components necessary to transfer a mouse between existing commercially available imaging systems to create a fusion between a whole-body anatomical ultrasound image, and a bioluminescence image. We will test this system in both a controlled in vitro environment, as well as a pilot small animal study implementing SonoVol's proprietary hardware. This SonoVol device allows any ultrasound probe to be manipulated around an animal to build up a cohesive whole-body 3D volume, as well as leverage several powerful image processing and analysis tools to align the two modalities, allowing one-to-one mapping between the anatomical and functional images. Furthermore, it will be possible to target ultrasound images, on-the-fly, to regions in the mouse's body which have strong bioluminescence signal expression. The next phase of commercialization of this product will be to build a dedicated system which does not require a physical transfer of the animal between systems, thereby further increasing throughput.
There are many methods currently used by researchers to collect images of preclinical animal models, including anatomical modalities (MRI, x-ray CT and ultrasound) and functional imaging modalities (SPECT, PET, and Optical). These two classes of imaging offer fundamentally different types of diagnostic information, and thus 'multi-modal' systems which can fuse the two, creating the most holistic picture of in vivo disease processes, enable researchers to longitudinally assess underlying disease processes, as well as tumor response to therapy (drug efficacy and toxicity studies) prior to administering drugs to humans. We are proposing to combine the fastest and least expensive modalities from each class (anatomical/functional) to create a hybrid-modality system which will combine the low cost high throughput advantages of ultrasound with the ubiquitous optical imaging approach. In the future, our benchtop hybrid-modality device should help reduce the cost and increase the pace of preclinical drug studies in both academic and industry settings by providing cheaper hardware and increased throughput.
