Magnetic resonance spectroscopy (MRS) is a powerful noninvasive tool in diagnoses, progressive monitoring, and studies of disease states of humans and animals. Point resolved spectroscopy (PRESS) and the stimulated echo acquisition mode (STEAM) technique have been extensively used to acquire localized one dimensional (1D) ¹H MRS. However, both PRESS and STEAM sequences, especially when they are performed with long echo times (TEs), can suffer from J modulations during TEs. In the Carr Purcell-selected PRESS (CPRESS) experiment, ¹ J modulations can be suppressed through quick repeating 180 pulses with short interpulse intervals at the cost of high radio frequency (RF) power deposition. In this study, we propose a modified pulse sequence called IP-PRESS for in-phase point resolved spectroscopy.

The schematic diagram of the IP-PRESS sequence is shown in Fig. 1. It starts with a 90º excitation pulse, and then follows with N repeated J-refocused modules which employ a 90º pulse at the midpoint of a double spin echoes. These repeated J-refocused modules are necessary for keeping J modulations suppressed at moderate or long TEs. The J-refocused module before acquisition, consisting of selective pulses along with slice selection and spoiler gradients along three orthogonal axes, is capable of achieving 3D spatial localization in one shot. In comparison with the standard PRESS sequence, additional pulses are employed by IP-PRESS sequence, especially at long TEs, resulting in increased RF power deposition. For suppressing J modulations, the interpulse intervals (τ₁ and τ₂) need to meet the requirement of τ << 1/J which can be much easier to reach in comparison with demands in the CPMG type sequences. ²

A sample of ethyl 3-bromopropionate (0.5M in CDCl₃) was utilized to test the performance of the IP-PRESS sequence. The voxel size was 4.0×4.0×16.0 mm³, and the repetition time was 4 s with no average. The interpulse intervals were set as τ₁ = τ₂ = 5 ms, and repetition number N were varied to obtain TEs from 20 to 500 ms with a step size of 20 ms. All experiments were performed on an 11.7 T Varian NMR System (Agilent Technologies, Santa Clara, CA, USA) with a 54 mm narrow bore, using a 5-mm indirect detection probe of 1.6 cm effective length at 298 K.

The IP-PRESS spectra of ethyl 3-bromopropionate are shown in Fig. 2a. Spectral peaks in IP-PRESS spectra almost keep in-phase with varied TEs. It suggests that J coupling modulations can be suppressed with IP-PRESS at achievable arbitrary echo times (TE). For typical metabolite T2 measurements, a series of MRS spectra are acquired with varying TEs. The signal intensities are quantified, and then used for exponential decaying fitting to obtain T2 values. With conventional MRS sequences, such as PRESS, signal intensities and phases of coupled resonances are modulated by J couplings with varying TEs, and thus signal quantification from acquired spectra cannot directly be used for exponential fitting. The IP-PRESS sequence suppresses J modulations at arbitrary TEs (see Fig. 2b), providing an approach for direct quantification and exponential fitting for scalar coupled peaks from acquired spectra.

In conclusion, the acquired IP-PRESS in-phase spectra are beneficial for reducing undesired broad resonances with short T2s at medium/long TEs and increasing signal intensities for J coupling metabolites. Moreover, they provide an approach of direct measurement of non-overlapping J coupling peaks at achievable arbitrary TEs and of their transverse relaxation times (T2).