Short TE downfield magnetic resonance spectroscopy in a mouse model of brain glioma

Abstract

Purpose: Enhanced cell proliferation in tumors can be associated with altered metabolic profiles and dramatic microenvironmental changes. Downfield magnetic resonance spectroscopy (MRS) has received increasing attention due to its ability to report on labile resonances of molecules not easily detected in upfield 1 H MRS. Image-selected-in-vivo-spectroscopy-relaxation enhanced MRS (iRE-MRS) was recently introduced for acquiring short echo-time (TE) spectra. Here, iRE-MRS was used to investigate in-vivo downfield spectra in glioma-bearing mice.Methods: Experiments were performed in vivo in an immunocompetent glioma mouse model at 9.4 T using a cryogenic coil. iRE-MRS spectra were acquired in N = 6 glioma-bearing mice (voxel size = 2.2 3 mm 3 ) and N = 6 control mice.Spectra were modeled by a sum of Lorentzian peaks simulating known downfield resonances, and differences between controls and tumors were quantified using relative peak areas.Results: Short TE tumor spectra exhibited large qualitative differences compared to control spectra. Most peaks appeared modulated, with strong attenuation of NAA (∼7.82, 7.86 ppm) and changes in relative peak areas between 6.75 and 8.49 ppm. Peak areas tended to be smaller for DF 6.83 , DF 7.60 , DF 8.18 and NAA; and larger for DF 7.95 and DF 8.24 . Differences were also detected in signals resonating above 8.5 ppm, assumed to arise from NAD+. Conclusions:In-vivo downfield 1 H iRE-MRS of mouse glioma revealed differences between controls and tumor bearing mice, including in metabolites which are not easily detectable in the more commonly investigated upfield spectrum.These findings motivate future downfield MRS investigations exploring pH and exchange contributions to these differences.

High‐field downfield MR spectroscopic imaging in the human brain

“…2,3 Another challenge is that DF resonances often also have short T 2 relaxation times, resulting in broad linewidths, overlapping peaks, and signal loss at longer TEs. 2,[4][5][6][7][8] Over the past decade, methods have been developed to measure and characterize DF resonances in human brain using B 0 field strengths at 3, 7, and 9.4T. 2,3,[9][10][11][12][13][14][15][16][17][18][19][20][21] An important principle is to avoid pre-saturation of water in order to maintain equilibrium magnetization of exchangeable DF peaks.…”

Downfield proton MRSI with whole‐brain coverage at 3T

“…3 Recently, small signals from I-tryptophan, a precursor of NAD(+) and serotonin syntheses, were also observed in DF MRS. 4 Although there have been comparatively few prior research studies using DF MRS, [5][6][7][8][9] there are some indications of potential in either clinical or preclinical applications. For instance, DF MRS has shown metabolic changes compared to normal brain in a murine brain glioma model, 10 and changes in phenylalanine levels measured in patients with phenylketonuria. 11 Also, estimations of brain pH have been shown to be feasible using the pH-dependence of the imidazole group resonances of histidine, with histidine levels increased using oral histidine supplementation.…”

Downfield Proton MRSI with whole-brain coverage at 3T

“…Although there have been comparatively few prior research studies using DF MRS, there are some indications of potential in either clinical or preclinical applications. For instance, DF-MRS has shown metabolic changes compared to normal brain in a murine brain glioma model (5), and changes in phenylalanine levels measured in patients with phenylketonuria (6). Also, estimations of brain pH have been shown to be feasible using the pH-dependence of the imidazole group resonances of histidine, with histidine levels increased using oral histidine supplementation (7).…”