Dr. John C. Giacomini
Palo Alto Veterans Affairs
3801 Miranda, 111-C
Palo Alto, CA 94304
Phone: 415-858-3932
Fax: 415-852-3473
Email: john.giacomini@forsythe.stanford.edu
Projects are approved by an IRB located at: Stanford University.
The approving IRB operates under a Multiple Project Assurance (MPA) recognized by DOE or by the Department of Health and Human Services (HHS).
MPA number of the IRB: M-1272-01
Number of Human Subjects Projects reported: 1
Project Identifier: SU-86-M-1272-01
Project Title:
K-Edge Subtraction Angiography with Synchrotron X-rays
Principle Investigator:
Dr. John C. Giacomini
Project started in: 1986
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
We received no incremental funds in FY 95. We are currently in year one of a no cost extension.
Project involves use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 2
Protocol/Subproject # 1
Protocol/Subproject Identifier: M-1272-01
IRB Review:
Type of Review: Full Board
Most Recent Approval: January 03, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
Objective: The development of a synchrotron based x-ray imaging method suitable for the acquisition of transvenous coronary angiograms. The hypothesis is that this method can provide coronary angiograms of quality comparable to those provided by conventional methods without the risks associated with arterial invasion and the direct injection of x-ray contrast agents into the ostia of the coronary arteries. This method with its reduced risk and increased capability would allow study of the progression of coronary artery disease and efficacy of current and new treatments. This is coupled with the long range goal of creating a diagnostic tool that is safe and accurate for clinical use on high risk subjects prior to onset of symptoms. Such a tool could provide physicians with early diagnosis allowing intervention that would result in increased life span and/or better quality of life for these subjects and a reduced burden on the national health care system in general.
Methodology: The method is based on the principle of iodine dichromography, using two beams of monochromatic x-rays whose energies closely bracket the K-edge absorption of iodine. In the case of coronary angiography, iodine contrast agent is injected into a vein and two images of the coronary arteries are acquired simultaneously using x-rays above and below the K-edge of iodine. An imaging of the coronary arteries is created by taking the logarithmic difference of the two images of different energies which virtually eliminates all signals except those arising from the contrast agent. The result is an image that gives high contrast details of the coronary arteries without interference from other structures such as bones which appear in standard x-ray techniques.
Ionizing radiation and chemical substances: The coronary angiography subject is injected intravenously with 35-50 milliliters (ml) of commercial iodinated contrast agent, 0.64 ml/kilogram (kg) at a rate of approximately 15 ml/second. The bronchography subjects are administered a maximum of 1 liter of medical grade 80% Xenon, 20% oxygen mixture in 100-300 ml boluses through inhalation. The subject in both cases is then imaged by moving the area of interest through two monochromatic x-ray beams that closely bracket the K-absorption edge of the contrast agent (33.16 keV for iodine and 34.56 keV for xenon). The subject receives a maximum of 35 Rad skin dose total for all images. Due to the high absorption of low energy (33-34 keV) x-rays by the surface layers of the skin, this translates into a small internal dose, the equivalent x-ray dose in this case would be 0.35 Rad.
Involvement of Human Subjects: The procedures here are performed on subjects that were referred by participating cardiologists or cardiovascular surgeons and have met the criteria set forth by the Stanford University and Brookhaven Laboratories Internal Review Boards (IRBs). The subjects participating in all studies suffer the potential risk of exposure to x-rays of the levels described above. The coronary angiography subjects suffer the additional risk of adverse effects of intravenous administration of iodinated contrast agents in total doses of 50-150 ml, given in bolus amounts of 15-50 ml. This risk entails acute renal failure or hypersensitivity reactions but is small in the population as a whole. Special care has been taken in selection criteria to exclude any subjects who have a high risk for adverse effect. These reactions are generally immediate and treatable, with no long term effects remaining.
Subject confidentiality will be maintained and no subject will be identified by name during any presentations or publications nor will any data concerning the subject be made available to anyone except members of the research team without the subject's prior consent.
IRB Review:
Type of Review: Full Board
Most Recent Approval: January 03, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 0
(Reporting periods vary.)
Type of Human Subjects Involvement:
Objective: A second project was initiated as an offshoot of the current coronary angiography project. This project, xenon dichromographic bronchography, relies on similar techniques and uses the same facilities to perform imaging of the bronchial airways using medical grade non-radioactive xenon gas as the contrast agent. Lung cancer today is one of the least curable cancers due to its late diagnosis, which results from late onset of symptoms and current imaging techniques lacking the ability to see small tumors before they have metastasized and become inoperable. The hypothesis here is that xenon's K-edge absorption energy is very close to that of Iodine, allowing the use of the same facility, and that xenon inhaled into the bronchial airways will provide a good contrast agent outlining the bronchial walls and emphasizing irregularities from tumors in the same manner that the iodine contrast agent emphasizes arterial stenosis. If this technique proves useful, it could become an easy and non-invasive way to screen high risk subjects and follow the course of current and new treatment methods to monitor their effectiveness.
Methodology: The method is based on the principle of Iodine dichromography, using two beams of monochromatic X-rays whose energies closely bracket the K-edge absorption of iodine. In the case of coronary angiography, iodine contrast agent is injected into a vein and two images of the coronary arteries are acquired simultaneously using X-rays above and below the K-edge of iodine. An imaging of the coronary arteries is created by taking the logarithmic difference of the two images of different energies, which virtually eliminates all signals except those arising from the contrast agent. The result is an image that gives high contrast details of the coronary arteries without interference from other structures, such as bones, which appear in standard X-ray techniques.
The xenon dichromographic bronchography uses exactly the same techniques as the iodine dichromographic angiography but uses xenon as a contrast agent requiring only a slight readjustment of the imaging equipment used in the iodine imaging to center the beam energies so that they bracket the xenon-K-edge instead of the iodine K-edge.
Ionizing radiation and chemical substances: The coronary angiography subject is injected intravenously with 35-50 ml of commercial iodinated contrast agent, 0.64 ml/kg at a rate of approximately 15 ml/s. The bronchography subjects are administered a maximum of 1 liter of medical grade 80% xenon, 20% oxygen mixture in 100-300 ml boluses through inhalation. The subject in both cases is then imaged by moving the area of interest through two monochromatic x-ray beams that closely bracket the K-absorption edge of the contrast agent (33.16 keV for iodine and 34.56 keV for xenon). The subject receives a maximum of 35 Rad skin dose total for all images. Due to the high absorption of low energy 33-34 keV X-rays by the surface layers of the skin this translates into a small internal dose, the equivalent x-ray dose in this case would be 0.35 Rad.
Involvement of Human Subjects: The procedures here are performed on subjects that were referred by participating cardiologists or cardiovascular surgeons and have met the criteria set forth by the Stanford University and Brookhaven IRBs. The subjects participating in all studies suffer the potential risk of exposure to x-rays of the levels described above. The coronary angiography subjects suffer the additional risk of adverse effects of intravenous administration of iodinated contrast agents in total doses of 50-150 ml, given in bolus amounts of 15-50 ml. This risk entails acute renal failure or hypersensitivity reactions but is small in the population as a whole. Special care has been taken in selection criteria to exclude any subjects who have a high risk for adverse effect. These reactions are generally immediate and treatable with no long-term effects remaining.
The subjects participating in the bronchography studies will suffer the additional risk of exposure to medical grade 80% xenon, 20% oxygen gas. Radioactive xenon has been approved for use on humans and is used clinically for studies of ventilation scanning. The effects of inhaled xenon are well known and present little risk. Xenon, as used in our imaging procedure, is non-radioactive and has little or no physiologic effect since only small amounts (less than 250 ml) are used and the xenon is inspired only into the dead space of the bronchial airways and remains there for only a few seconds with little or no xenon reaching the alveoli of the lungs.
Subject confidentiality will be maintained and no subject will be identified by name during any presentations or publications nor will any data concerning the subject be made available to anyone except members of the research team without the subject's prior consent.