This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Yttrium-89 does not find widespread use in the NMR community due to its low gyromagnetic ratio (approximately 5% of 1H) and, consequently, its low sensitivity. In spite of this limitation, 89Y does bring characteristics that would make it an excellent imaging agent. To begin with, the chemical shift dispersion can be greater than 100 ppm, implying that chelates sensitive to the local environment such as pH or [glucose] could be detected using chemical shift imaging (CSI). Secondly, 89Y has intrinsically long relaxation times - T1's of up to 8 minutes or more and T2's in the range of 60 ?100 ms have been measured. Long spin-lattice relaxation times dramatically expand the window over which hyperpolarized 89Y compounds can be delivered and consequently imaged, and also make 89Y an ideal choice for use in fly-back imaging techniques where the magnetization is restored along the Z-axis between acquisitions for resampling. Long spin-spin relaxation times make 89Y highly suitable for fast imaging schemes, such as the turbo spin echo, where numerous phase encodes can be conducted without significant loss of coherent transverse magnetization. Third, metabolically sensitive chelating agents specifically engineered for Gd3+, a powerful T1 relaxation agent, are likewise applicable to yttrium as the Y3+ ion is isoelectronic with Gd3+. Lastly, the 89Y nucleus is found in 100% abundance in nature. Even the inherently low sensitivity of 89Y can be overcome by the use of hyperpolarization via the dynamic nuclear polarization (DNP) method. Using a shallow 10 degree hard excitation pulse and 8 mM concentration of hyperpolarized Y(DOTA), initial spectroscopy results show that a 55:1 SNR and an enhancement of 1500 (with respect to 90 degree pulse acquired on a 3M thermal sample of YCl3) is possible via the DNP technique. These preliminary results indicate the successful application of hyperpolarized 89Y to imaging experiments to be very favorable. The hyperpolarized 89Y experiments of interest are those involving ex-vivo cardiac imaging of rat hearts. Regional ischemia can be induced in rat heart models to simulate the situation following a human myocardial infarction. By snaring the left anterior descending artery, the delivery of perfusate and hyperpolarized 89Y will be inhibited via this pathway, inducing temporary ischemia in the corresponding region of the myocardium. Upon imaging a cross section of the myocardium, bright regions will indicate the presence of hyperpolarized 89Y while dark regions will signify the locations of ischemia. To remove the possibility of motional artifacts while imaging, the heart can be arrested by mixing into the perfusate a 25 mM solution of KCl. In order to successfully image hyperpolarized 89Y in rat hearts, an appropriate rf probe and suitable imaging pulse sequences must be engineered. To accommodate a perfused rat heart hung in a perfusion column, a vertically oriented rf coil of approximately 20 mm in diameter must be built. Along with resonating at the desired 89Y frequency (19.6 MHz), this probe should be tunable to the proton frequency as well (400 MHz) to have the ability to collect proton scout images of the desired imaging plane. For the purposes of imaging hyperpolarized 89Y based upon chemical shift dispersion (as mentioned previously), 89Y CSI techniques would need to be developed. In order to preserve the hyperpolarized magnetization between acquisition pulses, fly-back sequences can be implemented. To rapidly collect multiple slices in various imaging planes, a fast imaging sequence can potentially be combined with a fly-back technique.
Showing the most recent 10 out of 374 publications
