Measurement of glycine in healthy and tumorous brain by triple‐refocusing MRS at 3 T in vivo

Abstract

Glycine (Gly) is implicated in several neurological disorders, including malignant brain tumors. Precise measurement of Gly is challenging largely due to the spectral overlap with myo-inositol (mI). We report a new triple-refocusing sequence for reliable co-detection of Gly and mI at 3T and evaluation of Gly in healthy and tumorous brain. The sequence parameters were optimized with density-matrix simulations and phantom validation. With a total TE of 134 ms, the sequence gave complete suppression of mI signal between 3.5 and 3.6 ppm and consequently well-defined Gly (3.55 ppm) and mI (3.64 ppm) peaks. In-vivo 1H MRS data were acquired from the gray-matter (GM) dominant medial-occipital and white-matter (WM) dominant left-parietal regions in six healthy subjects and analyzed with LCModel using in-house calculated basis spectra. Tissue segmentation was performed to obtain the GM and WM contents within the MRS voxels. Metabolites were quantified with reference to GM-rich medial occipital total creatine at 8 mM. The Gly and mI concentrations were estimated to be 0.63±0.05 and 8.6±0.6 mM for medial occipital and 0.34±0.05 and 5.3±0.8 mM for left parietal, respectively. From linear regression of the metabolite estimates versus fractional GM content, the concentration ratio between pure GM and pure WM was estimated as 2.6 and 2.1 for Gly and mI, respectively. Clinical application of the optimized sequence was performed in four subjects with brain tumor. The Gly levels in tumors were higher compared to healthy brain. Gly elevation was more extensive in a post-contrast enhancing region than in a non-enhancing region. Data indicated that the optimized triple-refocusing sequence may provide reliable co-detection of Gly and mI and alterations of Gly in brain tumors can be precisely evaluated.

Metabolomic prostate cancer fields in HRMAS MRS‐profiled histologically benign tissue vary with cancer status and distance from cancer

“…While ex vivo metabolomic evaluations can assist current clinical diagnosis and staging by providing biological information that cannot be obtained by histological evaluation, through the existence of cancer field effects, translating ex vivo findings to in vivo methods is the ultimate aim. A current challenge to this translation is that in vivo MRS studies typically focus on a select few, high‐intensity metabolites, primarily due to resolution constraints. Nevertheless, results from the examination of whole, cancerous prostates on a 7 T MR scanner indicated the potential of metabolomics for in vivo MRS, where metabolomic profiles measured from the removed prostates located cancer lesions with overall 93% accuracy .…”

Distinction of the GABA 2.29 ppm resonance using triple refocusing at 3 T in vivo

“…The 3D localized spectra of Glu and GABA were numerically calculated for 9 NS180 durations (14 to 30 ms, with 2‐ms increments) and for TE ( = τ 1 + τ 2 + τ 3 + τ 4 ) between 70 and 100 ms. The carrier frequency of NS180 was varied between 1 and 4.5 ppm with 0.5‐ppm increments, ensuring 180 ° rotation of resonances between 0.5 and 5 ppm by the NS180 (17 = kHz BW × ms duration), whose frequency profile is shown in our previous study . With 1‐ms increments for each of τ values that refocus the chemical shift evolution (i.e., τ 1 + τ 3 = τ 2 + τ 4 ), the total number of spectra was approximately 120 000 for each of GABA and Glu.…”

“…The carrier frequency of NS180 was varied between 1 and 4.5 ppm with 0.5-ppm increments, ensuring 180 8 rotation of resonances between 0.5 and 5 ppm by the NS180 (17 5 kHz BW 3 ms duration), whose frequency profile is shown in our previous study. 18 With 1-ms increments for each of s values that refocus the chemical shift evolution (i.e., s 1 1 s 3 5 s 2 1 s 4 ), the total number of spectra was approximately 120 000 for each of GABA and Glu. With broadening of the spectra to singlet linewidth of 4 Hz and use of GABA and Glu T 2 of 180 ms, 21 a sequence parameter set was searched for using the following criteria: (1) GABA C2-proton peak-to-peak amplitude greater than 95% of the zero-TE GABA C2-proton signal amplitude, (2) Glu C4-proton peak-to-peak amplitude greater than 60% of the zero-TE Glu C4-proton signal amplitude, and (3) small variation of Glu signal between 2.25 and 2.32 ppm.…”

“…Although a PRESS sequence can offer excellent separation between the GABA and Glu signals at 7 T, which is caused by the effects of the sub‐TE optimization on top of the enhanced spectral resolution of J‐coupled resonances at the high field, it is unlikely that at 3 T, distinction of the GABA 2.29 ppm signal from the Glu 2.35 ppm signal without sacrificing the Glu signal strength is straightforward by tailoring the PRESS sub‐TEs. A triple‐refocusing sequence (90 ° ‐ 180 ° ‐ 180 ° ‐ 180 °) has additional inter‐RF pulse time delays and thus provides a platform for amplifying the coherence evolution difference between spin resonances, as shown in our recent studies . In this study, we explore triple refocusing for detection of the GABA 2.29 ppm resonance at 3 T. For given RF envelopes, all possible components of the sequence, which included the 4 inter‐RF pulse time delays and the duration and carrier frequency of a non‐slice‐selective 180 ° RF pulse, were tailored, using density‐matrix simulations to achieve acceptable signal separation between the GABA C2‐proton and Glu C4‐proton resonances without considerable reduction of the signal strengths.…”

“…A triple-refocusing sequence (90 8 -180 8 -180 8 -180 8) has additional inter-RF pulse time delays and thus provides a platform for amplifying the coherence evolution difference between spin resonances, as shown in our recent studies. 17,18 In this study, we explore triple refocusing for detection of the GABA 2.29 ppm resonance at 3 T. For given RF envelopes, all possible components of the sequence, which included the 4 inter-RF pulse time delays and the duration and carrier frequency of a non-slice-selective 180 8 RF pulse, were tailored, using density-matrix simulations to achieve acceptable signal separation between the GABA C2-proton and Glu C4-proton resonances without considerable reduction of the signal strengths. Following validation of the GABA-optimized triple refocusing in a phantom solution, we tested the method in healthy subjects.…”