MR imaging of a novel NOE-mediated magnetization transfer with water in rat brain at 9.4 T

Abstract

Purpose: To detect, map, and quantify a novel nuclear Overhauser enhancement (NOE)-mediated magnetization transfer (MT) with water at approximately -1.6 ppm [NOE(-1.6)] in rat brain using MRI.

Methods: Continuous wave MT sequences with a variety of radiofrequency irradiation powers were optimized to achieve the maximum contrast of this NOE(-1.6) effect at 9.4 T. The distribution of effect magnitudes, resonance frequency offsets, and line widths in healthy rat brains and the differences of the effect between tumors and contralateral normal brains were imaged and quantified using a multi-Lorentzian fitting method. MR measurements on reconstituted model phospholipids as well as two cell lines (HEK293 and 9L) were also performed to investigate the possible molecular origin of this NOE.

Results: Our results suggest that the NOE(-1.6) effect can be detected reliably in rat brain. Pixel-wise fittings demonstrated the regional variations of the effect. Measurements in a rodent tumor model showed that the amplitude of NOE(-1.6) in brain tumor was significantly diminished compared with that in normal brain tissue. Measurements of reconstituted phospholipids suggest that this effect may originate from choline phospholipids.

Conclusion: NOE(-1.6) could be used as a new biomarker for the detection of brain tumor. Magn Reson Med 78:588-597, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Keywords: MRI; brain tumor; chemical exchange saturation transfer (CEST); magnetization transfer (MT); nuclear Overhauser enhancement (NOE).

Fig. 1

CEST Z-spectra (a) and CEST residual spectra (b) with B₁ of 0.5 μT (red), 1.0 μT (blue), and 1.5 μT (green) from three healthy rat brains. Black lines in (a) are the reference signals obtained with the Lorentzian fit of background direct water saturation and MT effects. Note that the NOE(−1.6) is not easily identified from the Z-spectra in (a), but can be identified from the CEST residual spectra in (b). Also note in (b) that the NOE(−1.6) signal (arrow) is optimized at B₁ of 1.0 μT. Regions of interest (ROIs) were drawn from the whole brain. Error bars are the standard deviations across subjects.

Fig. 2

AREX residual spectra (magenta), fitted NOE(−1.6) peak (blue), and fitted NOE(−3.5) peak (green) from nine healthy rat brains. Note that the NOE(−1.6) peak can be isolated from the NOE(−3.5) peak by using Lorentzian fit. Regions of interest (ROIs) were drawn from the whole brain. Error bars are the standard deviations across subjects.

Fig. 3

Left column: anatomic image to show the four ROI (C: Cortex; CC: Corpus Callosum; CP: Caudate Putamen; SC: Singular Cortex) (a) and pixel-by-pixel fitted maps for amplitude (b), resonance frequency offset (c), and line width (d) of the NOE(−1.6) signal from a healthy rat brain. Right column: averaged Z-spectra from the four ROIs (a) and the statistical analysis of amplitude (b), resonance frequency offset (c), and line width (d) of the NOE(−1.6) signal from nine healthy rat brains. (n=9)

Fig. 4

Statistics of amplitude of NOE(−1.6) (a), offset of NOE(−1.6) (b), line width of NOE(−1.6) (c), amplitude of NOE(−3.5) (d), offset of NOE(−3.5) (e), line width of NOE(−3.5) (f), R_1obs (g), and PSR (h) from tumors and contralateral normal tissue from eight rat brains bearing 9L tumors. (n=8, **P<0.01, *P<0.001 )

Fig. 5

Images of amplitude of NOE(−1.6) (a), amplitude of NOE(−3.5) (b), R_1obs (c), and PSR (d), as well as T₂ weighted image (e) from a representative rat brain bearing a 9L tumor. Note the tumor indicated by the red arrow in (a).

Fig. 6

Z-spectra from reconstituted Egg PC with TE of 1.1 ms (a), a variety of TEs (b), fitted amplitude of NOE(−1.6) as a function of TE (c), and Z-spectra from cultured HEK293 and 9L cell lines (d).