SBIR-STTR Award

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 Statement:


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.

Project Terms:
Abdomen; Abscess; absorption; Adopted; American; Anatomy; Animal Model; Attenuated; Barium; base; Biocompatible; Blood Vessels; Calculi; Clinical; Color; commercialization; Complex; Contrast Media; cost; Cost Savings; Data; Development; Diagnosis; Diagnostic; Diagnostic Errors; Disease; Dose; drug development; Drug Formulations; Drug Kinetics; Effectiveness; Emergency Situation; Enteral; FDA approved; Foundations; Gastrointestinal Diseases; Goals; Head; Health Care Costs; Healthcare Systems; Hemorrhage; high risk; Image; improved; In Vitro; in vivo; Individual; Inflammatory; Intestines; Intravenous; Iodine; Ischemia; Low Dose Radiation; Measures; Medical; Medical Errors; novel; Oral; Oranges; Organ; Outcome; Phase; Polymers; pre-clinical; preclinical efficacy; preclinical evaluation; Preclinical Testing; Property; Protocols documentation; public health relevance; Radiation; radiologist; Rattus; Research; Resolution; Roentgen Rays; Route; Rupture; Safety; Scanning; Series; Signal Transduction; Silicon; Silicones; Small Business Technology Transfer Research; soft tissue; Speed (motion); Testing; Tomography, Computed, Scanners; Toxic effect; Trauma; uptake; X-Ray Computed Tomography

Our long term goal is to revolutionize the effectiveness of CT imaging for millions of Americans across a broad range of abdominal disease. Dual energy CT (DECT) provides powerful clinical diagnostic potential but remains heavily underutilized despite wide scanner availability. DECT allows materials to be differentiated based on their relative X-ray attenuation at low versus high energy X-ray spectra. Unfortunately, current DECT workflow is highly fragmented: None of the 3rd party Picture Archiving and Communications Systems (PACS) that physicians use to view clinical images can process DECT images; each DECT scanner's images can only be processed by that specific scanner vendor's software. Worse, DECT signal units are scanner-specific and not compatible with historical 120 kVp single energy CT (SECT) Hounsfield Units (HU) which remain the most commonly used CT signal unit today, and the basis of most diagnostic CT threshold criteria. The profound future of multi-contrast DECT, whereby multiple simultaneously imaged contrast agents are separated at DECT to give rich diagnostic information of complex anatomy, also remains unrealized. Commercial DECT software fails in quantitative separation of current iodine contrast from novel high-Z and silicon agents. In our STTR Phase I we developed a novel Contrast Material Extraction Process (CMEP) that vividly separates individual contrast agent signals, including that of calcium, at DECT. We propose to further validate these methods across all commercial clinical DECT scanner types and integrate them into an urgently needed Vendor-Agnostic DECT processing Software (VADS) for wide low-cost distribution and integration into clinical PACS workflow. Our overall hypothesis is that images from each of the four available clinical DECT scanner types can be processed and displayed using a common interface, and this interface can allow quantitative scan comparisons between all DECT and SECT scanners through a Unified 120 kVp SECT-like HU. Once FDA-approved, VADS will enable FDA-approval of many urgently needed DECT contrast agents to fulfill the promise of multi-contrast DECT. Our Specific Aims are to 1) Construct standardized DECT phantoms spanning the range of human tissues and contrast agents currently available and in development to obtain a comprehensive image library for each of the commercial clinical DECT scanners; 2) Implement and validate VADS on this image library to allow all DECT images to be processed in a common software interface designed to be 510(k) approvable and readily integrated into PACS or other 3rd party viewing workstations; 3) Use the image library to define a "Unified Hounsfield Unit," compatible with 120 kVp SECT, to allow all DECT scanner types and SECT, regardless of kVp setting, to be quantitatively compared. At the conclusion of this proposal, we will have developed disruptive 510(k) approvable software to streamline daily clinical DECT workflow and provide necessary infrastructure for future transformative highly diagnostic multi-contrast enhanced DECT.

Public Health Relevance Statement:
NARRATIVE The clinical implementation of dual energy CT is obstructed by fragmented software interfaces in current clinical radiology workflow and software-imposed limitations on capability. We will interrogate dual energy CT imaging with each of the commercially available clinical scanners to develop disruptive vendor-agnostic software that will streamline dual energy image processing, improve material separation capability, allow quantitative comparison of images from all CT scanners, and allow double contrast-enhanced dual energy CT to give richly detailed co-registered images of complex abdominal anatomy for millions of Americans at a low radiation dose and major cost savings to the healthcare system. Terms: