The proposed Bioengineering Research Partnership will integrate bioengineering, basic science and clinical efforts in the design, development and clinical validation of a high-transition-temperature (high Tc; operating at 77oK) superconducting susceptometer for the direct, non-invasive measurement of hepatic iron stores in patients with iron overload from hereditary hemochromatosis, thalassemia major, sickle cell disease and other disorders. Our laboratories originally proposed that storage iron (ferritin and hemosiderin) could be non-invasively assessed in vivo because of its paramagnetic properties. We subsequently developed low-transition-temperature (low Tc; operating at 4.2oK) superconducting quantum interference device (SQUID) biosusceptometry as a clinical method for the measurement of hepatic iron stores. Non-invasive magnetic measurements of hepatic storage iron in patients with iron overload are quantitatively equivalent to biochemical determinations on tissue obtained by biopsy but the cost and complexity of the low-Tc instrument has restricted clinical adoption of the method. Our low-Tc susceptometer has three elements which utilize superconductivity: (i) the SQUID, (ii) the field coils that produce a localized steady magnetic field near the liver, and (iii) the detection coils and flux transformer. Recent technological advances make possible replacement of each of these low-Tc elements, cooled by liquid helium, with components able to function when cooled by liquid nitrogen. To provide """"""""proof-of-principle,"""""""" we have constructed and operated a prototype high-Tc susceptometer with (i) a high-Tc SQUID, (ii) a NdBFe permanent magnet providing a strong localized magnetic field, and (iii) detection coils and flux transformer fashioned from a high-Tc Y1Ba2Cu3O7-delta film deposited on a flexible substrate. The proposed Partnership will now optimize and integrate these components into a series of liquid nitrogen-cooled clinical devices, and then validate and certify the high Tc-susceptometers in studies of adult and pediatric patients. Magnetic studies permit accurate, direct, and repeated measurements of hepatic iron stores not possible with any other method. The development of an affordable, readily usable instrument for the non-invasive measurement of hepatic iron - a high priority goal of both the NIDDK and the NHLBI - would be a major advance in the diagnosis and management of patients with iron overload that would find immediate and widespread clinical use both in the U.S. and worldwide.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK057209-03
Application #
6607128
Study Section
Special Emphasis Panel (ZRG1-BBCB (01))
Program Officer
Badman, David G
Project Start
2001-09-30
Project End
2006-04-30
Budget Start
2003-08-01
Budget End
2004-04-30
Support Year
3
Fiscal Year
2003
Total Cost
$865,305
Indirect Cost
Name
Columbia University (N.Y.)
Department
Pediatrics
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032