On-resonance low B1 pulses for imaging of the effects of PARACEST agents.

Application of the exchange-sensitive, low-power RF pulses positioned on the bulk water resonance for imaging of the effects of PARACEST agents is proposed as an alternative to the standard CW off-resonance irradiation. Specifically, we applied a low-power WALTZ-16 RF train, with the 90 degrees pulse unit replaced by a pulse of the fixed length (WALTZ-16*). Using this sequence, the bulk water signal was found to be sensitive to exchange lifetimes with PARACEST complex bound protons, the transverse relaxation time of bulk water, and longitudinal relaxation time of bound protons. In this report, the concept of using WALTZ-16* to "activate" a PARACEST effect is introduced and some of the salient features of this technique with respect to experimental conditions and performance levels are discussed. Computational predictions are verified and explored by comparison with experimental spectroscopic and imaging data. It is shown that WALTZ-16* can be used to detect PARACEST agents with an RF intensity as low as 200 Hz for concentrations as low as a few tens of microM for lanthanide chelates having appropriate water-exchange rates (Tm,Dy).

[1]  S. Aime,et al.  A new class of contrast agents for magnetic resonance imaging based on selective reduction of water-T2 by chemical exchange , 1988 .

[2]  R S Balaban,et al.  Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST) , 2000, Magnetic resonance in medicine.

[3]  R S Balaban,et al.  Imaging of urea using chemical exchange‐dependent saturation transfer at 1.5T , 2000, Journal of magnetic resonance imaging : JMRI.

[4]  A Dean Sherry,et al.  The amide protons of an ytterbium(III) dota tetraamide complex act as efficient antennae for transfer of magnetization to bulk water. , 2002, Angewandte Chemie.

[5]  Enzo Terreno,et al.  Novel pH-reporter MRI contrast agents. , 2002, Angewandte Chemie.

[6]  S. Meiboom,et al.  NUCLEAR MAGNETIC RESONANCE STUDY OF THE PROTON TRANSFER IN WATER , 1961 .

[7]  A. Sherry,et al.  Physical characteristics of lanthanide complexes that act as magnetization transfer (MT) contrast agents , 2003 .

[8]  Enzo Terreno,et al.  Paramagnetic Lanthanide(III) complexes as pH‐sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications , 2002, Magnetic resonance in medicine.

[9]  A. J. Shaka,et al.  Evaluation of a new broadband decoupling sequence: WALTZ-16 , 1983 .

[10]  M. Garwood,et al.  Product operator analysis of the influence of chemical exchange on relaxation rates. , 2004, Journal of magnetic resonance.

[11]  A. Sherry,et al.  A novel europium(III)-based MRI contrast agent. , 2001, Journal of the American Chemical Society.

[12]  A. J. Shaka,et al.  Broadband spin decoupling in isotropic-liquids , 1987 .

[13]  A. Palmer,et al.  On the use of the stochastic Liouville equation in nuclear magnetic resonance: Application to R1ρ relaxation in the presence of exchange , 2003 .

[14]  A Dean Sherry,et al.  A paramagnetic CEST agent for imaging glucose by MRI. , 2003, Journal of the American Chemical Society.

[15]  Robert E Lenkinski,et al.  PARACEST agents: modulating MRI contrast via water proton exchange. , 2003, Accounts of chemical research.

[16]  Jinyuan Zhou,et al.  Quantitative description of proton exchange processes between water and endogenous and exogenous agents for WEX, CEST, and APT experiments , 2004, Magnetic resonance in medicine.

[17]  Matthew E Merritt,et al.  Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI , 2005, Magnetic resonance in medicine.

[18]  G. Bodenhausen,et al.  Principles of nuclear magnetic resonance in one and two dimensions , 1987 .

[19]  D. Woessner,et al.  Nuclear Transfer Effects in Nuclear Magnetic Resonance Pulse Experiments , 1961 .

[20]  R S Balaban,et al.  A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). , 2000, Journal of magnetic resonance.

[21]  J. Bulte,et al.  Sensitive NMR detection of cationic-polymer-based gene delivery systems using saturation transfer via proton exchange. , 2001, Journal of the American Chemical Society.

[22]  R. Henkelman,et al.  Understanding pulsed magnetization transfer , 1997, Journal of magnetic resonance imaging : JMRI.

[23]  Enzo Terreno,et al.  A paramagnetic MRI-CEST agent responsive to lactate concentration. , 2002, Journal of the American Chemical Society.

[24]  H. Mcconnell.  Reaction Rates by Nuclear Magnetic Resonance , 1958 .

[25]  A. J. Shaka,et al.  An improved sequence for broadband decoupling: WALTZ-16 , 1983 .

[26]  A. Palmer,et al.  An average-magnetization analysis of R 1ρ relaxation outside of the fast exchange limit , 2003 .

[27]  A. Sherry,et al.  Unusually sharp dependence of water exchange rate versus lanthanide ionic radii for a series of tetraamide complexes. , 2002, Journal of the American Chemical Society.

[28]  Susumu Mori,et al.  Mechanism of magnetization transfer during on‐resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids , 2003, Magnetic resonance in medicine.

[29]  R. Balaban,et al.  Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo , 1989, Magnetic resonance in medicine.

[30]  Bob S. Hu,et al.  Pulsed saturation transfer contrast , 1992, Magnetic resonance in medicine.

[31]  E. Schneider,et al.  Pulsed magnetization transfer versus continuous wave irradiation for tissue contrast enhancement , 1993, Journal of magnetic resonance imaging : JMRI.

[32]  P. V. van Zijl,et al.  Water exchange filter with improved sensitivity (WEX II) to study solvent-exchangeable protons. Application to the consensus zinc finger peptide CP-1. , 1996, Journal of magnetic resonance. Series B.

[33]  Jinyuan Zhou,et al.  Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI , 2003, Nature Medicine.