SBIR-STTR Award

Our long term goal is to revolutionize the effectiveness of computed tomography (CT) imaging for millions of Americans across a broad range of gastrointestinal disease. Bowel and intravenous contrast agents are critical for CT imaging of abdominal disease. Unfortunately, none of the current clinical contrast agents 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 of CT leads to ambiguous images that cost over $2B in medical errors annually in the USA. We present dramatic preclinical in vivo data showing that novel oral silicone agents can be delivered concurrently with yet be easily differentiated from current iodinated intravenous agents to give simultaneous, high-resolution, perfectly co-registered CT images of the bowel and vasculature in a single pass of a DECT scanner. Such double contrast-enhanced DECT scans provide richly detailed interrogation of anatomy at lower radiation dose than a conventional CT scan, eliminate protocol errors, accelerate diagnoses, and will dramatically reduce health care costs. Our agent is disruptive because silicone has not been previously described as an X-ray attenuating material for CT. Our development pathway is straightforward and ideal for the SBIR Fast Track program because our agent shows dramatic efficacy, high safety, and does not alter the normal workflow of CT imaging. Our prototype agent already shows favorable preclinical safety results over that of available barium agents. DECT scanners are increasingly clinically available. Our overall hypothesis is that a novel silicon-based material is suitable for use as the first DECT bowel contrast agent for differentiation from other agents. Our Specific Aims are to 1) Perform stepwise preclinical toxicity tests on three candidate variants of our lead agent to select a final formulation for development; 2) Obtain scaled-up clinical Good Manufacturing Practice formulation and Good Laboratory Practice toxicity tests in rat and dog to achieve FDA-IND approval; 3) Demonstrate that our bowel contrast material is safe healthy volunteers in Phase 1 Clinical trials; 4) Confirm that our bowel contrast material is readily differentiated from iodinated agents by DECT in a Phase 2 Clinical trial. (Aim 1= "SBIR Phase I"; Aims 2-4 = "SBIR Phase II" of the Fast Track program). At the conclusion of this proposal, we will have shown safety of the first silicone bowel DECT contrast agent in healthy human volunteers and shown disruptive imaging efficacy for double contrast enhanced DECT. These key data will enable subsequent Clinical Phase 3 tests of our DECT agent in appropriate patients with abdominal disease to catalyze a frame-shift in CT imaging -- increased speed, accuracy, and confidence of CT imaging diagnoses for everyday abdominal scenarios at reduced cost to the healthcare system and lower radiation dose.

Public Health Relevance Statement:


Public Health Relevance:
Though contrast agents are critical to medical CT imaging, over $2 billion in medical errors occur annually from our inability to differentiate between bowel and intravascular contrast agents at imaging. We will develop the first safe clinical bowel contrast agent that is visibly distinct from all current intravascular agents at dual energy CT. Ths safe and efficacious clinical bowel contrast agent will 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:

?Our long term goal is to revolutionize the effectiveness of computed tomography (CT) imaging for millions of Americans across a broad range of gastrointestinal disease. Bowel and intravenous contrast agents are critical for CT imaging of abdominal disease. Unfortunately, none of the current clinical contrast agents 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 of CT leads to ambiguous images that cost over $2B in medical errors annually in the USA. We present dramatic preclinical in vivo data showing that novel oral silicone agents can be delivered concurrently with yet be easily differentiated from current iodinated intravenous agents to give simultaneous, high-resolution, perfectly co-registered CT images of the bowel and vasculature in a single pass of a DECT scanner. Such double contrast-enhanced DECT scans provide richly detailed interrogation of anatomy at lower radiation dose than a conventional CT scan, eliminate protocol errors, accelerate diagnoses, and will dramatically reduce health care costs. Our agent is disruptive because silicone has not been previously described as an X-ray attenuating material for CT. Our development pathway is straightforward and ideal for the SBIR Fast Track program because our agent shows dramatic efficacy, high safety, and does not alter the normal workflow of CT imaging. Our prototype agent already shows favorable preclinical safety results over that of available barium agents. DECT scanners are increasingly clinically available. Our overall hypothesis is that a novel silicon-based material is suitable for use as the first DECT bowel contrast agent for differentiation from other agents. Our Specific Aims are to 1) Perform stepwise preclinical toxicity tests on three candidate variants of our lead agent to select a final formulation for development; 2) Obtain scaled-up clinical Good Manufacturing Practice formulation and Good Laboratory Practice toxicity tests in rat and dog to achieve FDA-IND approval; 3) Demonstrate that our bowel contrast material is safe healthy volunteers in Phase 1 Clinical trials; 4) Confirm that our bowel contrast material is readily differentiated from iodinated agents by DECT in a Phase 2 Clinical trial. (Aim 1= "SBIR Phase I"; Aims 2-4 = "SBIR Phase II" of the Fast Track program). At the conclusion of this proposal, we will have shown safety of the first silicone bowel DECT contrast agent in healthy human volunteers and shown disruptive imaging efficacy for double contrast enhanced DECT. These key data will enable subsequent Clinical Phase 3 tests of our DECT agent in appropriate patients with abdominal disease to catalyze a frame-shift in CT imaging -- increased speed, accuracy, and confidence of CT imaging diagnoses for everyday abdominal scenarios at reduced cost to the healthcare system and lower radiation dose.

Public Health Relevance Statement:


Public Health Relevance:
Though contrast agents are critical to medical CT imaging, over $2 billion in medical errors occur annually from our inability to differentiate between bowel and intravascular contrast agents at imaging. We will develop the first safe clinical bowel contrast agent that is visibly distinct from all current intravascular agents at dual energy CT. Ths safe and efficacious clinical bowel contrast agent will 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.

NIH Spending Category:
Bioengineering; Clinical Research; Clinical Trials and Supportive Activities; Diagnostic Radiology; Digestive Diseases; Patient Safety

Project Terms:
Abdomen; absorption; Adverse event; American; Anatomy; Animal Model; Attenuated; Award; Barium; base; Biocompatible; Biological; Blood Vessels; bone; Canis familiaris; Clinical; Clinical Trials; Color; commercialization; Complex; contrast enhanced; Contrast Media; cost; Cost Savings; Cyclic GMP; Data; Development; Diagnosis; diagnostic accuracy; Diagnostic Errors; Disease; Dose; drug development; Effectiveness; efficacy testing; Emulsions; Enteral; experience; Formulation; Frequencies; Gastrointestinal Diseases; Goals; good laboratory practice; Health; Health Care Costs; Healthcare Systems; healthy volunteer; Hemorrhage; high risk; Human Volunteers; Image; improved; in vivo; Ingestion; Intestines; intraperitoneal; Intravenous; Iodine; Kidney; Lead; Liver; Low Dose Radiation; Medical; Medical Errors; Monitor; Muscle; novel; Oils; Oral; Oranges; Organ; Pathway interactions; Patients; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Phase III Clinical Trials; Polymers; pre-clinical; preclinical safety; preclinical toxicity; prevent; Process; programs; Property; Protocols documentation; prototype; Radiology Specialty; Rattus; Research; Resolution; Roentgen Rays; Rupture; Safety; safety testing; Sagittaria; Sales; scale up; Scanning; Serum; Severities; Signal Transduction; Silicon; Silicone Oils; Silicones; Small Business Innovation Research Grant; soft tissue; Speed; Spleen; Stomach; subcutaneous; Testing; Time; Tomography, Computed, Scanners; Toxic effect; Toxicity Tests; Translations; Trauma; uptake; Variant; X-Ray Computed Tomography