Association of Choline Levels and Tumor Perfusion in Brain Metastases Assessed with Proton MR Spectroscopy and Dynamic Susceptibility Contrast-enhanced Perfusion Weighted MRI

Abstract

While malignant brain tumors typically show high choline concentrations and neovascularity, we have anecdotally noted that a substantial number of brain metastases from lung cancer demonstrate only mildly elevated choline resonances on proton MR spectroscopy (¹ H-MRS). The goals of this study were to determine whether lung cancer metastases are more likely to demonstrate low choline than other metastases and, in addition, to assess the relationship between choline and tissue perfusion in brain metastases. We performed a retrospective analysis of 66 patients with untreated brain metastases (40 NSCLC; 17 breast cancer; 9 melanoma) who underwent multivoxel 2D-CSI ¹ H-MRS. Cho/Cr was compared between histologies using Mann-Whitney U tests. Lesions were dichotomized into low and high Cho/Cr groups, and differences in relative Cho/Cr between groups were assessed with Fisher's exact tests. 21 patients also underwent dynamic susceptibility MR perfusion weighted imaging (PWI). Normalized relative cerebral blood volume ratios (rCBV_norm) were calculated, and strength of correlation between Cho/Cr and rCBV_norm was assessed. Cho/Cr was significantly lower in lung cancer metastases compared to breast cancer metastases. Cho/Cr < 2.0 was observed in 37.5% of lung cancer metastases, 23.5% of breast cancer metastases, and 0% of melanoma metastases. Lung cancer metastases were significantly more likely to demonstrate low Cho/Cr than melanoma metastases (p = 0.04). There was a strong correlation between Cho/Cr and rCBV_norm (ρ = 0.847, p < 0.001), and metastases in the high Cho/Cr group showed significantly higher rCBV_norm. These findings suggest that choline metabolism and tumor perfusion in brain metastases are interrelated, and we posit that this relationship may be due to the influence of the transcription factor HIF-1.