Our long term goal is to revolutionize the safety and effectiveness of computed tomography (CT) imaging for millions of Americans across a broad range of gastrointestinal disease. Bowel and intravenous contrast materials improve the CT imaging of abdominal disease. Unfortunately, none of the current clinical contrast materials are visibly different from the others at imaging, even on modern dual energy CT (DECT) scanners, because all agents are based on iodine or barium which attenuate X-rays similarly across different X-ray spectra. This limitation leads to ambiguous images that cost over $2B in medical errors annually in the USA. We now have dramatic preclinical in vivo data showing that novel oral silicone materials can be delivered concurrently with yet be easily differentiated from current iodinated intravenous agents to produce simultaneous, high-resolution, perfectly co-registered CT images of the bowel and vasculature in a single pass of the DECT scanner. Such double contrast-enhanced DECT scans give rich abdominal anatomic detail at lower radiation dose than a conventional CT scan, eliminate protocol errors, increase the speed of diagnosis, and will dramatically reduce health care costs. Our agent is disruptive because silicone has not previously been described as an X-ray attenuating material for CT contrast agents. Since DECT scanners are already clinically available and conventional enteric contrast is already widely used, a dramatically improved silicone enteric contrast should be rapidly adopted once FDA approved. Our overall hypothesis is that a novel silicone contrast agent is safe, reduces radiation dose, and provides richly detailed anatomic images in a single DECT scan that cannot be achieved with conventional CT contrast agents.
The Specific Aims of our project are to test the hypotheses that 1) Enteric silicone contrast agents show minimal if any systemic uptake;2) CT scans obtained with enteric silicone-based contrast material and automated exposure control require less radiation dose than with conventional enteric contrast agents;3) DECT obtained with enteric CT contrast and intravenous iodinated contrast provide substantially more information on contrast material concentration and distribution than when obtained with conventional barium and iodinated agents in vitro and in vivo. These key data will be the foundation for subsequent development of this powerful DECT agent to catalyze a frame-shift in CT imaging that will increase the speed, accuracy, and confidence of CT imaging diagnosis for everyday abdominal scenarios with reduced cost to the healthcare system and lower radiation dose.

Public Health Relevance

Over $2 billion in medical errors occur annually from the inability of bowel and intravascular contrast agents to be differentiated from each other at clinical CT imaging. We will perform preclinical evaluation of a new class of bowel contrast agent that will be the first to be visibly distinct from all current intravascular agents at dual energy CT. This safe and efficacious clinical bowel contrast agent will allow double contrast-enhanced dual energy CT to generate richly detailed co-registered images of complex abdominal anatomy and potentially benefit millions of Americans at a low radiation dose and major cost savings to the healthcare system.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
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Special Emphasis Panel (ZRG1-SBIB-T (10))
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Densmore, Christine L
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Nextrast, Inc.
United States
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Lambert, Jack W; Sun, Yuxin; Ordovas, Karen G et al. (2018) Improved Calcium Scoring at Dual-Energy Computed Tomography Angiography Using a High-Z Contrast Element and Novel Material Separation Technique. J Comput Assist Tomogr 42:459-466
Dotson, Brandan; Lambert, Jack W; Wang, Zhen J et al. (2017) Benefit of iodine density images to reduce out-of-field image artifacts at rapid kVp switching dual-energy CT. Abdom Radiol (NY) 42:735-741
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Winklhofer, Sebastian; Lambert, Jack W; Wang, Zhen Jane et al. (2016) Reduction of peristalsis-related gastrointestinal streak artifacts with dual-energy CT: a patient and phantom study. Abdom Radiol (NY) 41:1456-65
Dhatt, Harpreet S; Behr, Spencer C; Miracle, Aaron et al. (2015) Radiological Evaluation of Bowel Ischemia. Radiol Clin North Am 53:1241-54