Short echo time relaxation‐enhanced MR spectroscopy reveals broad downfield resonances

Abstract

Purpose Most MR spectroscopy (MRS) pulse sequences rely on broadband excitation with water saturation and typically focus on upfield signals. By contrast, the downfield spectrum, which contains many potentially useful resonances, is typically not targeted because conventional water‐suppressed techniques indirectly saturate the labile protons through exchange. Relaxation‐enhanced MRS (RE‐MRS) uses frequency‐selective excitation while actively avoiding bulk water perturbation, thereby enabling high‐quality downfield spectroscopy. However, RE‐MRS typically requires very long (typically >40 ms) echo times (TEs) due to its localization module, which inevitably decreases sensitivity and filters shorter T2 components. Here, we overcome this limitation by combining RE‐MRS and image selected in vivo spectroscopy (ISIS) localization, abbreviated iRE‐MRS, which in turn allows very short TEs (5 ms using our hardware). Methods Experiments were performed in vitro for validation as well as and in in vivo rat brains at 9.4T. Results The new iRE‐MRS methodology was validated in phantoms where good performance was noted. When the downfield spectrum was investigated at short TEs in in vivo rat brains, iRE‐MRS provided very high sensitivity; the ensuing downfield spectra encompassed numerous broad peaks, as well as a broad baseline. All downfield spectral peaks were highly attenuated by increasing TEs as well as by applying water saturation, although to different extent. The signal ratios also varied between TEs, suggesting that exchange rates are different among the downfield signals. Conclusions Short‐TE iRE 1H downfield MRS opens new directions in the investigation of in vivo downfield metabolites and their role on healthy and disease processes.

Non‐water‐excitation MR spectroscopy techniques to explore exchanging protons in human brain at 3 T

“…A similar TE was achieved for 7 T with a 3D‐localizing triple‐echo sequence with optimized Shinnar‐Le Roux refocusing pulses 25 . The nWE method with the shortest reported TE so far was suggested by Gonçalves et al 28 for use in rat brain at 9.4T. It was similar to our 3D I‐CSE method, first reported at about the same time in Ref.…”

“…Also, the peaks further upfield (at 5.8, 6.1 and 6.3 ppm) are much less prominent in the I‐CSE spectra, although that is likely just due to the excitation profile and possibly also an effect of artifacts arising from imperfect water cancelation in MC and residual water excitation with I‐CSE. However, the nWS spectrum from the literature that is most comparable with ours is the one from rat brain also obtained with an ISIS technique 28 . In this case, the 8.1‐8.5ppm peaks are as prominent in comparison to the 7.8ppm peak as in the nWS I‐CSE spectrum in Figure 8.…”

“…Almost all of the above nWE techniques are efficiently preventing saturation transfer, but their rather long TEs lead to undesirable T 2 ‐relaxation‐related signal loss. Minimal TEs can be achieved with ISIS, which has recently been optimized for downfield resonances in rats at 9.4 T 28 …”

“…10 Almost all of the above nWE techniques are efficiently preventing saturation transfer, but their rather long TEs lead to undesirable T 2relaxation-related signal loss. Minimal TEs can be achieved with ISIS, which has recently been optimized for downfield resonances in rats at 9.4 T. 28 The aim of the current study is to explore new ways to detect downfield metabolite signals from exchangeable protons at the clinical field strength of 3 T. One is based on 3D ISIS and the other on 2D ISIS in combination with a frequency-and slice-selective spin echo. In addition, the results are compared with spectra obtained via MC-based nWS MRS.…”

In vivo characterization of downfield peaks at 9.4 T: T2 relaxation times, quantification, pH estimation, and assignments

“…Peaks between 8.0 and 8.4 ppm have been described by the literature as fast decaying amide resonances 2,6,36,43 . The measured exchange times (~10‐30 s −1 ) and resonance frequency (3.5 ppm in CEST) of these peaks closely match those of the amide proton transfer resonances measured with CEST 2,4,36,45,46 .…”