Abstract
PurposeHyperpolarized 15N‐labeled molecules have been proposed as imaging agents for investigating tissue perfusion and pH. However, the sensitivity of direct 15N detection is limited by the isotope's low gyromagnetic ratio. Sensitivity can be increased by transferring 15N hyperpolarization to spin‐coupled protons provided that there is not significant polarization loss during transfer. However, complete polarization transfer would limit the temporal window for imaging to the order of the proton T1 (2‐3 s). To exploit the long T1 offered by storing polarization in 15N and the higher sensitivity of 1H detection, we have developed a pulse sequence for partial polarization transfer.MethodsA polarization transfer pulse sequence was modified to allow partial polarization transfer, as is required for dynamic measurements, and that can be implemented with inhomogeneous B1 fields, as is often the case in vivo. The sequence was demonstrated with dynamic spectroscopy and imaging measurements with [15N2]urea.ResultsWhen compared to direct 15N detection, the sequence increased the signal‐to‐noise ratio (SNR) by a factor of 1.72 ± 0.25, where both experiments depleted ~20% of the hyperpolarization (>10‐fold when 100% of the hyperpolarization is used). Simulations with measured cross relaxation rates showed that this sequence gave up to a 50‐fold increase in urea proton polarization when compared to spontaneous polarization transfer via cross relaxation.ConclusionThe sequence gave an SNR increase that was close to the theoretical limit and can give a significant SNR benefit when compared to direct 13C detection of hyperpolarized [13C]urea.
Highlights
Magnetic resonance imaging of hyperpolarized isotopically labeled substrates has enabled measurements of metabolic fluxes, pH, and tissue perfusion in vivo
Hyperpolarized 15N-labeled substrates have been investigated, as agents for assessing tissue perfusion and as pH probes.4 15N labeled substrates have the advantage of very long hyperpolarization lifetimes, up to 200 s, and more when kept in 2H2O.2
Equation 10 can be used when comparing the signalto-noise ratio (SNR) of a direct detection experiment with a 90° pulse with an indirect detection experiment in which all the available polarization is transferred with perfect efficiency to the coupled high γ nucleus
Summary
Magnetic resonance imaging of hyperpolarized isotopically labeled substrates has enabled measurements of metabolic fluxes, pH, and tissue perfusion in vivo. The sequence was simulated with the delays and phases used experimentally (τ1 + τ2 = 0.442/(2 π JNH) = 782 μs, τ3 + τ4 = 1/(2 JNH) = 5555 μs, δ = 18.050°), which resulted in 21% of the 15N polarization being transferred to 1H and a 1H z-magnetization that was 1.78 times greater than the initial 15N z-magnetization (Figure 2B).
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