Vasomotor fluctuations are increased in primary central nervous system lymphoma: a case-control study with fast functional MRI.

Primary CNS lymphoma is an aggressive brain tumour. An accumulation of malignant cells around cerebral blood vessels may potentially impair the convection of cerebrospinal fluid within perivascular spaces. Recent evidence links an increased variation of the blood oxygen level-dependent signal, a marker for haemodynamic changes, to risk of mortality in lymphoma. In this study, we aimed to characterize the physiological source(s) of increased blood oxygen level-dependent signal variation in lymphoma and characterize the link between altered physiological pulsations and mortality. Thirty lymphoma patients (median age 66 years; 9 females) and 40 healthy age-matched controls (median age 62 years; 29 females) were scanned using an ultrafast functional MRI sequence. We extracted physiological brain pulsation frequency bands from functional MRI data: full band (0.008-5 Hz), very low frequency (0.008-0.1 Hz), respiratory (0.1-0.5 Hz) and cardiac (0.7-2 Hz). We compared the respective pulsation amplitudes between groups using non-parametric covariate-adjusted permutation tests and studied the link between region-specific pulsation amplitudes and mortality in receiver-operating characteristic (ROC) and survival analyses. The lymphoma group showed higher amplitudes in all brain pulsation bands ( ≤ 0.05), with a global increase in the very-low-frequency band. Additionally, we detected increased fluctuation amplitudes in regions extending beyond the macroscopically visible tumour areas. The very-low-frequency and respiratory bands showed a link to mortality in the lymphoma patients, very-low-frequency band being independent of other predictive markers. Increased very-low-frequency amplitude, reflecting propagating vasomotor waves, was the main source for the increased blood oxygen level-dependent signal variation in lymphoma. The patients dying during follow-up showed higher very-low-frequency and respiratory amplitudes compared with the surviving patients, implicating them as a potential prognostic marker.