Association between metabolic parameters from dynamic 18f-fluoromethylcholine pet, pharmacokinetic parameters from dce-mri, choline to creatine ratios from mrs and tissue immunohistochemistry for choline kinase alpha expression in human brain glioma

INTRODUCTION: Proton MR spectroscopy and Choline-PET probe different aspects of choline metabolism, and quantitative dynamic MRI yields information on vascular permeability and perfusion. The relationship between these features in different grades of glioma is, however, unclear. METHOD: 14 patients with suspected primary supratentorial glioma were recruited to this study. The mean values over the whole tumour (T2-FLAIR hyperintense regions) of DCE-derived pharmacokinetic parameters were correlated with tumour to background ratio (TBR: ratio of SUVmax in tumour to SUVmean in contralateral white matter for the 7-17-minute static PET images). Dynamic PET macroparameters were quantified with spectral analysis (SA) in six patients for whom metabolite data were available. Choline to creatine ratios (Cho/Cr) were extracted from 2D-CSI data over 257 MRS voxels and correlated with TBR. Tissue immunohistochemistry for choline kinase alpha expression in targeted biopsies was carried out in regions of tumour with high and low uptake on PET and Cho/Cr on MRS. RESULTS: We observed a positive significant correlation between DCE-MRI derived parameters and parameters obtained through SA of the dynamic choline-PET data as well as TBR. We also observed a positive significant correlation between MRS Cho/Cr and TBR, although this was weak when excluding WHO Grade IV tumours. We did not observe a strong correlation between choline markers on imaging and choline kinase alpha expression. CONCLUSION: The correlation between both DCE and MRS parameters with TBR indicates that a number of biological features affect the uptake of the PET tracer. DCE-MRI provides complimentary information to blood volume and permeability that may augment interpretation of PET data; and help address questions such as the degree to which tracer uptake is dominated by blood brain barrier permeability rather than metabolic activity. Choline imaging with PET and MRS may reflect metabolic processes that are not simply related to choline kinase alpha expression.