Development of a mobile and automated platform for multiplexed multi-modality imaging

Abstract Bioluminescence imagingBLIsystems are installed in thousands of facilities and labsand with their straightforward and low cost workflow for longitudinal studiesare the most commonly used preclinical modality for assessing tumor models in rodentsThere currently is no high throughput and low cost system enabling BLI images to be combined with anatomical images of soft tissue to confirm tumor volumecontextor vascularityIn our Phase I workwe demonstrated the feasibility of mapping data from our whole body ultrasoundUSsystem toD BLI imagesThe additional US data dramatically reduced inter user quantification variability of the BLI signalandgtFurthermorewe showed that our clinically translatable microvessel imaging technologyacoustic angiographycan be mapped to the BLI dataThose tumor microvessels were analyzed using patented vessel analysis algorithmsyielding quantifiable vascular morphology metricspreviously shown to be reliable predictors of tumor malignancy and response to therapy in humansThus our commercialized hybrid modality US BLI devicethe Alpheidae Platformwill allow angiogenic tumors and anti angiogenic therapies to be studied in ways current in vivo imaging tools do not allowIn Phase IIwe propose to bring the Alpheidae Platform to marketleveraging whole body tissue and vascular US imaging to improve cancer research with BLIThe team includes experts in optical imaging system designphotoacoustic system designand US imaging system designSpecificallyin Phase IIwe will address the following aimsAimHardware Randamp D for multi animal tri modality imagingSix animals will be scanned sequentially by our robotic system in each of the three modesThroughput for six animals will be andltminAimSoftware and algorithm Randamp D to enable automated targeted US and PA acquisitions based on BLI imagesand leveraging algorithms for improved spatial resolution in both US and PA datasetsAimValidation studies within in vivo tumor drug response studyDevice performance will be assessed by comparison to standard BLI in a murine breast cancer modelIts capacity to reliably predict eventual drug response within one week of starting therapy will be the criteria for successOnce Phase II is completed we will have created a novel high throughput and portable tool enabling tumor tissue and microvessel images to be mapped to BLI dataImportantly from a commercial perspectivethe Alpheidae Platform can be sold for a fraction of what competitive systems costFrom a translational research perspectivethe device includes a clinically translatable US microvessel imaging approach for tumor assessmentand thus forms a direct link between preclinical findings in mice and actionable clinical cancer assessment protocols Project Narrative Bioluminescence imaging is the most commonly used preclinical modality for assessing tumor models in rodentsThese optical imaging systems are installed in thousands of labs across the USAWe propose to extend upon these systemsfunctionality with the added ability to bothavisualize internal anatomical structuressuch as organ and tumor boundariesusing ultrasound andbquantify molecularly targeted agents inD alongside the ultrasound using photoacousticsA tumor s blood supply will also be quantified using a patented imaging approach calledacoustic angiographywhich is not currently available in a commercial multi modality productThis system s simple workflow will improve usability by researchersdecreasing interuser variability and improving data integrity in cancer research and drug studiesIn Phase I we proved feasibility for our systemIn Phase II we will conduct the Randamp D necessary to commercialize the system for improved cancer research and preclinical trials of experimental cancer therapies