Low sensitivity is particularly problematic in heteronuclear MRI, where insensitive and/or dilute heteronuclear spins are detected. A general spin amplification scheme was developed to enhance the sensitivity of heteronuclear spins based on dynamic instability of the solvent magnetization under collective feedback fields. The heteronuclear solute spins are first detected by the solvent proton spins through various magnetization transfer mechanisms and serve as small “input” signals to perturb the solvent proton magnetization, which is prepared in an unstable state. The weakly detected signal is then amplified through subsequent nonlinear evolution of the solvent proton magnetization. By manipulating bulk solvent proton spins near the threshold of instability to detect dilute heteronuclear solute spins, sensitivity and signal-to-noise ratios (SNR) of the heteronuclear MR spectroscopy and imaging can be markedly improved.

This general indirect-detection and spin-amplification scheme (Fig. 1) has been developed to amplify indirectly detected heteronuclear solute signals. Low-gyromagnetic ratio nuclei can be detected through the large solvent ¹H magnetization by the distant dipolar field (DDF) [1,2]. As shown in Fig. 1, the modulated ¹H transverse magnetization precesses under the DDF created by the spatially modulated ¹³C longitudinal magnetization, generating an echo in the ¹H solvent magnetization that carries information about the ¹³C spins. Recently discovered self-refocusing of dephased solvent magnetization due to the joint action of radiation damping and the DDF [2] is exploited to enhance the indirectly detected echo signal. The extreme sensitivity of the first and largest self-refocused echo's phase and amplitude to the phase and amplitude of the initial triggering magnetization (here, the indirectly detected signal) suggests that the nonlinear spin dynamics can serve as a high-gain spin amplifier to enhance the small initial magnetization transferred to the solvent from the dilute ¹³C solute spins.

This general spin amplification scheme is shown here to amplify indirectly detected heteronuclear solute signals. Low-gyromagnetic ratio nuclei can be detected through the large ¹H solvent magnetization by the distant dipolar field (DDF) [1,2]. As shown in Fig. 1 (pulse sequence at top, a+b), the modulated ¹H transverse magnetization precesses under the DDF created by the spatially modulated ¹³C longitudinal magnetization, generating an echo in the ¹H solvent magnetization that carries information about the ¹³C spins. Recently discovered self-refocusing of dephased solvent magnetization due to the joint action of radiation damping and the DDF [3] is exploited to enhance the indirectly detected echo signal. The extreme sensitivity of the first and largest self-refocused echo's phase and amplitude to the phase and amplitude of the initial triggering magnetization (here, the indirectly detected signal) suggests that the nonlinear spin dynamics can serve as a high-gain spin amplifier to enhance the small initial magnetization transferred to the solvent from the dilute ¹³C solute spins. The resulting SNR of the amplified indirectly detected echo signal, e.g., 10% 2-¹³C acetone solution, is improved by ~3-4x (Fig. 2b) compared to without amplification (Fig. 2a, DDF only).

The amplification factor can be further improved by controlling the nonlinear spin evolution under the feedback fields. For example, if the ¹H pulse flip angle >90°, the instability of the inverted net ¹H longitudinal magnetization under radiation damping aids in refocusing more ¹H transverse magnetization. The resulting SNR is enhanced by an additional 4x, as demonstrated on U-¹³C glucose (Fig. 3). Moreover, field inhomogeneity or weak continuous gradients may also be exploited to accelerate the self-refocusing process [3] and increase SNR by more than 10x overall (Fig. 2c).Application of this approach to ¹³C MRI is shown in Fig. 4 and Fig. 5 for a K¹³CN phantom sample and in vivo carrot stem, respectively.Sensitivity enhancement by the dynamic instability of solvent proton magnetization represents a new direction for surmounting a long-standing weakness of poor sensitivity in heteronuclear MRS and MRI.