In vivo (1)H MRSI of glycine in brain tumors at 3T

Abstract

Purpose: MR spectroscopic imaging (SI) of glycine (Gly) in the human brain is challenging due to the interference of the abundant neighboring J-coupled resonances. Our aim is to accomplish reliable imaging of Gly in healthy brain and brain tumors using an optimized MR sequence scheme at 3 tesla.

Methods: Two-dimensional (1)H SI was performed with a point-resolved spectroscopy scheme. An echo time of 160 ms was used for separation between Gly and myo-inositol signals. Data were collected from eight healthy volunteers and 14 subjects with gliomas. Spectra were analyzed with the linear combination model using numerically calculated basis spectra. Metabolite concentrations were estimated with reference to creatine in white matter (WM) regions at 6.4 molar concentrations (mM).

Results: From a linear regression analysis with respect to the fractional gray matter (GM) content, the Gly concentrations in pure GM and WM in healthy brains were estimated to be 1.1 and 0.3 mM, respectively. Gly was significantly elevated in tumors. The tumor-to-contralateral Gly concentration ratio was more extensive with higher grades, showing ∼ 10-fold elevation of Gly in glioblastomas.

Conclusion: The Gly level is significantly different between GM and WM in healthy brains. Our data indicate that SI of Gly may provide a biomarker of brain tumor malignancy.

Keywords: 1H MRSI; 3T; PRESS (point-resolved spectroscopy); glycine; human brain, gliomas.

FIG. 1

SI and SVS data were acquired with PRESS TE = 160 ms from a phantom containing Gly (1.1 mM), mIns (10 mM) and Cr (10.0 mM). (a) The FOV (blue line; 160 × 160 mm²) and VOI (brown line; 50 × 50 mm²) are shown in a gradient echo image. Fine grids indicate the individual voxels of the SI. (b) Spectra from the VOI are presented between 2.7 and 4.2 ppm. (c,d) SI and SVS spectra and LCModel fitting results. Vertical dashed lines are drawn at 3.55 and 3.62 ppm. Data were acquired using a TR of 3000 ms. The SI data were acquired with a single average for each k-space point, while the SVS spectrum was acquired with 256 signal averages. The spectra are broadened to singlet linewidth of ~3 Hz.

FIG. 2

Representative ¹H SI data from a healthy volunteer. (a, b) The FOV (blue line) and VOI (brown line) of the SI are shown in T₁w-MPRAGE images. The VOI was prescribed by PRESS localization (TE = 160 ms). Fine grids indicate the individual voxels of the SI. The mean tCr estimate over the voxels within a red line was set to 6.4 mM after CSF correction and used as reference for metabolite quantification. (c) Spectra from voxels within the VOI are shown between 4.1 to 1.0 ppm. (d, e) Spectra from a voxel in the gray matter (blue box) and from a voxel in the white matter (green box) dominant regions are shown together with LCModel fits, baseline, and residuals that were obtained using basis sets with and without Gly. The Gly and mIns signals, returned by LCModel, are shown with the concentration estimates and CRLBs. Vertical lines are drawn at 3.55 ppm.

FIG. 3

(a) Concentration and CRLB maps of Gly, mIns, and tCr for the VOI (green box in a T₁w-MPRAGE image), averaged over eight healthy volunteers. The maps were smoothened by eight fold using a bi-cubic polynomial function, after the corrections for theCSF contamination and chemical-shift displacement effects. Averaged Gly-mIns correlation coefficients (returned by LCModel) are mapped on linear scale between −0.5 and 0.5. (b) Gray matter and white matter segmented brain images are shown with the SI VOI. (c, d) Linear regression of Gly and mIns tissue concentrations with respect to fractional GM contents from a single subject. Dashed lines indicate 95% confidence intervals of the linear fit.

FIG. 4

Numerically-calculated spectra and LCModel fitting results are shown for Gly-to-mIns = 1:10 (a) and 1:20 (b). Spectra were broadened to singlet linewidth of 3.5 – 7.5 Hz and random noise was added to the spectra such that the ratio of the NAA singlet amplitude to the noise standard deviation was 50 for all the linewidths. The metabolites include Gly (1 and 0.3 in (a) and (b) respectively), mIns (10 and 6 in (a) and (b) respectively), NAA (10), Cr (8), Cho (2), Glu (9), and Gln (2), where the numbers in brackets are the concentrations.

FIG. 5

SI data from a subject with multi-focal glioblastoma. Spectra from tumors (labeled A and C) and the corresponding contralateral locations (labeled B and D) are shown together with spectral analysis results. The concentrations of Gly and mIns were estimated with reference to the mean tCr estimate within a black box in the T₂w-FLAIR image at 6.4 mM.

FIG. 6

The mean Gly and tCho concentrations in the tumor and contralateral brain regions in 5 grade II, 4 grade III, and 5 grade IV gliomas are bar graphed with standard deviations. The contralateral estimates in grade IV were calculated from 3 patients, excluding 2 patients in whom the tumor was located in brainstem. Statistical significance is shown for p < 0.05, with an asterisk (*) for paired t-test and a dagger (†) for unpaired t-test.