DMSO as a potential contrast agent for brain tumours

MATERIALS AND METHODS: Nine C57BL/6 female mice were used in this study, 3 wild-type (WT) mice and six glioma-bearing mice induced as described in [4]. MRI studies were carried out at 7T in a horizontal magnet, anesthetizing the animals with isoflurane (1.5-2.0 %), monitoring their breathing pattern and controlling their rectal temperature (37oC). Initially, TMZ was diluted in DMSO and administered by an intragastric probe to three WT mice used as controls. The administration vehicle was DMSO in saline (10%). Standard T2-weighted MRI scout images (TR/TEeff= 4200/36ms) and PRESS single-voxel (SV) (2.5mm) spectra (TE=12 and 136ms) were acquired from the striatum before and after a single dose administration of TMZ solution. This protocol was performed at different times after treatment to calculate the DMSO wash-out curve in normal brain. Afterwards, the same protocol was applied to three GL261 glioma-bearing mice to further investigate the acute effects of the DMSO in their brain tumour spectral pattern. Only the administration vehicle was used in this case. SV-MRS postprocessing was performed with MestRec software (Mestrelab Research SL). The areas of selected metabolites were normalized to unsuppressed water and used for quantification. The other 3 tumour-aflicted mice were studied by MRSI before and after vehicle administration, which was injected intraperitoneally (i.p.) to avoid re-shimming needs. A reference T2W image and 12 ms TE control MRSI were initially acquired. DMSO was then injected (0min_PI_DMSO), followed by 14 repeated 12ms TE MRSI acquisitions, interleaved with two 136ms TE MRSI at 110min_PI_DMSO and 242min_PI_DMSO. Parameters for PRESSMRSI: 1.76x1.76x1.0cm FOV; 5.5x5.5x1.0mm VOI; 512 scans; 32x32 reconstructed matrix (4.84μl nominal resolution); 2500ms TR (21m30s acquisition time), 12 ms TE; signal sampled with 2k points. MRSI grids were post-processed with 3DiCSI [5] and exported in ASCII format to MatLab (home-written scripts) to generate time-course maps of brain MR-detectable DMSO changes based on peak heights. Statistical analysis used was ANOVA, setting significance at p<0.05.