National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
NIDDK Workshop on Noninvasive Measurement of Iron
April 17, 2001 • Bethesda, MD
| Tuesday, April 17
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| 8:00 a.m. | Registration |
| 8:45 a.m. | Opening Remarks David Badman, DKUHD, NIDDK, National Institutes of Health Allen Spiegel, Director, NIDDK, National Institutes of Health Frank Somma, National President, Cooley’s Anemia Foundation, Inc. |
| 9:00 a.m. | Session I. Clinical Needs for Measurement of Iron
Chair: Gary Brittenham, Columbia University, NY Panelists Roland Fischer, UKE - Abt. Medizinische Biochemie Elliott P. Vichinsky, Children's Hosp. Oakland Res Institute Alan R. Cohen, Children's Hospital of Philadelphia Harriet C. Isom, Penn State College of Medicine, Hershey Med Center |
| 10:00 a.m. | Session II. Physical Properties of Iron Chair: Philip Aisen, Albert Einstein College of Medicine Panelists Alvin L. Crumbliss, Duke University Gary Buettner, University of Iowa Denny N. Chasteen, University of New Hampshire at Durham |
| 11:00 a.m. | Session III. Detection of Iron Overload by MRI Chair: Thomas Mareci, Director, Center for Structural Biology, University of Florida Panelists Rodney Brooks, NIH Evan S. Siegelman, University of Pennsylvania George Bartzokis, University of Arkansas at Little Rock Zhiyue J. Wang, Children’s Hospital of Philadelphia Pierre Gillis, Faculté De Méd,Univ De Mons-Hainaut Herbert Bonkovsky, University of Massachusetts Medical School Tim St. Pierre, University of Western Australia Jeff Bulte, NIH Peter Van Gelderen, NIH |
| 1:00 p.m. | Session IV. Detection of Iron Overload by Susceptometry (magnetometry)
Chair: David E. Farrell, Case Western Reserve University Panelists Gary M.Brittenham, Columbia University Joseph L. Kirschvink, California Institute Of Technology Paul N. Arendt, Superconductivity Technology Center Sankaran Kumar, Quantum Magnetics William Avrin, Quantum Magnetics Douglas Paulson, Tristan Technologies Roland Fischer, UKE - Abt. Medizinische Biochemie Ronald B. Goldfarb, NIST |
| 2:00 p.m. | Session V. Discussion and Recommendations Chair: Robert Balaban, National Institutes of Health |
| 4:00 p.m. | Adjourn |
Participants
Philip Aisen |
William F. Avrin Consultant in Applied Physics Quantum Magnetics, Inc. 7740 Kenamar Court San Diego, CA 92121 Tel: (858)549-9431 Fax: (858)566-9388 Bavrin@ucsd.edu |
| Robert S. Balaban Scientific Director for Laboratory Research National Heart Lung, and Blood Institute, Building 10, Room 7N214 National Institutes of Health 10 Center Drive MSC 1668 Bethesda, MD 20892-1668 Tel: (301)496-2116 Fax: (301)435-1842 rsb@nih.gov |
Herbert Bonkovsky Professor of Medicine, Biochemistry & Molecular Biology Director The Liver , Biliary Pancreatic Center University of Massachusetts Medical School 55 Lake Avenue North, Room S6-737 Worcester, MA 01655 Tel: (508)856-3068 Fax: (508) 856-3981 Bonkovsh@ummhc.org |
| Gary Brittenham Professor of Pediatrics and Medicine Pediatrics Department, Health Sciences Division Columbia University, College of Physicians and Surgeons 630 West 168th Street, Harkness Pavilion, Room HP550 New York, NY 10032-3795 Tel: (212)305-7005 Fax: (212)305-8408 Gmb31@columbia.edu |
Jeff Bulte Staff Scientist Building 10, Room B1N256, MSC 1074 National Institutes of Health 10 Center Drive Bethesda, MD 20892 Tel: (301)402-4547 Fax: (301)594-2979 jwmbulte@helix.nih.gov |
| N. Dennis Chasteen Waite Professor of Chemistry Department of Chemistry University of New Hampshire Parsons Hall, UNH Durham, NH 03824 Tel: (603)862-2520 Fax: (603)862-2520 Ndc@cisunix.unh.edu |
Alvin L. Crumbliss Professor of Chemistry Department of Chemistry Duke University Box 90346 Durham, NC 27708-0346 Tel: (919)660-1540 Fax: (919)660-1605 alc@chem.duke.edu |
| Roland Fischer UKE-Inst. Medizinische Biochemie Martinistr. 52 20246 Hamburg, Germany Tel: 011-49-40-42803-4798 Fax: 011-49-40-42803-4797 Fischer@uke.uni-hamburg.de |
Richard B. Frankel Professor of Physics Department of Physics, College of Science and Math, Building #052, Science Room #E14 California Polytechnic State University 1 Grand Avenue San Luis Obispo, CA 93407 Tel: (805)756-1666 Fax: (805)756-2435 rfrankel@calpoly.edu |
| Ronald B. Goldfarb Magnetics Group Leader Department of Electromagnetic Tech Division NIST Room 1232, 325 Broadway, Mailcode 814.05 Boulder, CO 80305 Tel: (303)497-3650 Fax: (303)497-5316 Goldfarb@boulder.nist.gov |
Joseph L. Kirschvink Professor of Geobiology California Institute of Technology M.S. 170-25, 1200 E California Boulevard Pasadena, CA 91125 Tel: (626)395-6136 Fax: (626)568-0935 Kirschvink@caltech.edu |
| Maren Laughlin Metabolism and Structural Biology Program Director DEMD/NIDDK National Institutes of Health 2 Democracy Plaza, Room 6101 Bethesda, MD 20892 Tel: (301)594-8802 laughlinm@extra.niddk.nih.gov |
Phyllis Mitchell NHLBI/DBDR National Institutes of Health Rockledge Center Two, Room 10163, 6701 Rockledge Drive, MSC 7950 Bethesda, MD 20892--7950 Tel: (301)435-0481 Fax: (301)480-1060 mitchelp@nhlbi.nih.gov |
| Jayne Restivo National Executive Director Cooley's Anemia Foundation, Inc. 129-09 26th Avenue Flushing, NY 11354 Tel: 800-522-7222 or 718-321-2873 Fax: (718)321-3340 Jrestivo@aol.com |
Evan S. Siegelman Department of Radiology University of Pennsylvania 3400 Spruce Street, 1st Floor Silverstein, Room 1-11 Philadelphia, PA 19104-4283 Tel: (215)662-3034 Fax: (215)662-3013 Siegelm@rad.upenn.edu |
| Tim St. Pierre Department of Physics The University of Western Australia Crawley, WA Australia 6009 Tel: 61-8-9430-8971 Fax: 61-8-9380-1014 stpierre@physics.uwa.edu.au |
Elliott Vichinsky Director, Hematology/Oncology Department of Hematology Children's Hospital Oakland 747 52nd Street Oakland, CA 94609 Tel: (510)428-2286 Fax: (510)450-5647 evichinsky@mail.cho.org |
| Dr. Weglicki National Institutes of Health Bethesda, MD 20892 |
Paul Arendt Superconductivity Technology Center Los Alamos National Laboratory Mail Stop K763 Los Alamos, NM 87545 Tel: (505)667-0358 Arendt@mst-mail.lanl.gov |
| David Badman Hematology Program Director, Deputy Director for Basic Program Administration DKUHD, NIDDK National Institutes of Health 2 Democracy Plaza, Room 621 MSC 5458, 6707 Democracy Blvd. Bethesda, MD 20892-5458 Tel: (301)594-7717 Fax: (301)480-3510 db70f@nih.gov |
George Bartzokis Associate Professor of Psychiatry Department of Psychiatry University of Arkansas for Medical Sciences CAVHS, 2200 Fort Roots Drive-(116) North Little Rock, AR 72114 Tel: (501)257-3098 Fax: (501)257-2024 Gbar@ucla.edu |
| Josie Briggs Director, DKUHD, NIDDK Building 31, Room 9A17 National Institutes of Health Bethesda, MD 20892 Tel: (301)496-6325 BriggsJ@extra.niddk.nih.gov |
Gary Buettner University of Iowa ESR Facility, Emrb 68 Iowa City, IA 52242-1101 Tel: (319)335-6749 Fax: (319)335-8049 Gary.Buettner@uiowa.edu |
| Nunzio Cazzetta Cooley's Anemia Foundation, Inc. 129-09 26th Avenue Flushing, NY 11354 Tel: (718)321-2873 Fax: (718)321-3340 Alan R. Cohen |
Chief Division of Hematology Children's Hospital of Philadelphia 34th Street & Civic Center Boulevard Philadelphia, PA 19104-4318 Tel: (215)590-3438 Fax: (215)590-3525 Cohen@email.chop.edu |
| David Farrell Professor of Physics Physics Department Case Western Reserve University Rockefeller Building Cleveland, OH 44106 Tel: (216)368-2615 Fax: (216)368-4671 Def@po.cwru.edu |
Joseph Frank Building 10, Room B1N256 National Institutes of Health Bethesda, MD Tel: (301)402-3586 Fax: (301)402-3216 Jf5z@nih.gov |
| Pierre Gillis Professor Physique Biologique University of De Mons-Hainaut Faculte de Medecine, Avenue Du Champ De Mars, 24 Mons, Belgium B 7000 Tel: 011-32-65-373537 Fax: 011-32-65-373537 Pierre.gillis@umh.ac.be |
Harriet C. Isom Assistant Dean and Director of the MD/PhD Program; Distinguished Professor of Microbiology and Immunology; Professor of Pathology Microbiology & Immunology Department Penn State University College of Medicine 500 University Drive Hershey, PA 17033 Tel: (717)531-8609 Fax: (717)531-4133 Hisom@psu.edu |
| Sankaran Kumar Senior Scientist Quantum Magnetics, Inc. 7740 Kenamar Court San Diego, CA 92069 Tel: (858)566-9200 Fax: (858)566-9388 sankaran.kumar@qm.com |
Thomas H. Mareci Associate Professor Department of Biochemistry and Molecular Biology College of Medicine, University of Florida PO Box 100245 Gainesville, FL 32610-0245 Tel: (352)392-3375 Fax: (352)392-3422 Thmareci@ufl.edu |
| Douglas Paulson President Tristan Technologies 6350 Nancy Ridge Drive, Suite 102 San Diego, CA 92014 Tel: (858)550-2720 Fax: (858)550-2722 Paulson@tristantech.com |
Tracey Rouault Head, Section on Human Iron Metabolism Cell Biology and Metabolism Branch, NICHD, Bldg. 18, Room 101 National Institutes of Health Bethesda, MD 20892 Tel: (301)496-6368 Fax: (301)402-0078 |
| Frank Somma President Cooley's Anemia Foundation, Inc. 27 Schanck Road Holmdel, NJ 07733 Tel: 800-800-6387 Fax: (201)858-8046 Fsomma@candlebusiness.com |
Peter Van Gelderen Building 10, Room B1D317 National Institutes of Health Bethesda, MD Tel: (301)402-1472 Fax: (301)402-1009 Pg24y@nih.gov |
| Zhiyue Jerry Wang Associate Member Department of Radiology The Children's Hospital of Philadelphia 34th Street and Civic Center Boulevard Philadelphia, PA 19104 Tel: (215)590-3556 Fax: (215)590-4127 Wang@email.chop.edu |
Ellen M. Werner Health Scientist Administrator Division of Blood Diseases and Resources, National Heart Lung and Blood Institute National Institutes of Health 6701 Rockledge Drive, Rm 10182, MSC 7950 Bethesda, MD 20892-7950 Tel: (301)435-0077 Fax: (301)480-1046 wernere@nhlbi.nih.gov |
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Background There is a pressing need to be able to perform non-invasive measurements of body iron stores. The need has been recognized for a long time in thalassemia patients who receive chronic blood transfusions. More recently, sickle cell patients at risk for stroke have been transfused more regularly, and there has been consideration of iron measurements in individuals with hemochromatosis mutations. There are numerous other conditions where such measurement might be useful. Serial measurements of plasma ferritin have had some utility, but are highly variable from one individual to the next. These needs have been recognized in NIDDK Congressional language in recent fiscal years, and related projects have been funded through the SBIR program. For many years, thalassemia patients have had their liver iron stores assessed using a SQUID (superconducting quantum interference device), which has been shown to correlate well with biopsy results. Until recently, there has been only one SQUID in the U.S., formerly in Cleveland and now about to become operational in New York City. This device is a very sensitive detector of magnetic fields, but is expensive and cumbersome to operate. A more affordable and more readily usable instrument could be designed with advanced technology, but design and testing will take several years. The SQUID technology is unlikely to be useful in assessing iron stores in the heart, in which the effect of body iron burden is most severe. Other technology has been suggested to perform such measurements. The most prominently mentioned alternative is magnetic resonance imaging (MRI). MRI equipment is widely available, but there are questions of standardization of measurements among various facilities. MRI measurements depend upon the complex interactions of several iron-binding proteins and water protons that are incompletely understood. Also, MRI sensitivity appears to be decreased at higher level of iron, limiting its utility in heavily loaded individuals. Several other methods have been proposed, with less likelihood of clinical utility, including nuclear resonance scattering of X-rays and computed tomography (CT). A workshop is proposed to air the issues involved in non-invasive iron measurement, and to help the NIDDK design the most effective approach to non-invasive iron measurement in patients. Some of the issues to be addressed: What each method measures
Target organs Sensitivity needed How measurements scale from animal models to humans Clinical correlations and goals
False positives and negatives Studies needed to validate each technology
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