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

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.

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 = 2.2³  mm³ ) 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.

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+.

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.