The Regulation of Vasomotor and Cardiorespiratory Pulsations Is Disrupted in Primary Central Nervous System Lymphoma:...

Primary central nervous system lymphoma (PCNSL) alters (peri)vascular structures while increasing vasomotor and cardiorespiratory pulsations within the brain. Vasomotor pulsations may arise from amplitude modulations of respiratory (RPE) and cardiovascular (CHE) pulsations while cardiovascular fluctuations may be modulated by respiration through cardiorespiratory amplitude modulation (CREM). In this study, we examined glymphatic cerebrospinal fluid convection in brains of PCNSL patients by assessing these waves. Thirty PCNSL patients (median 66y; 9 females) and 40 healthy age-matched controls (median 62y; 29 females) were scanned using an fMRI-based MREG_BOLD sequence. Respective MREG_BOLD fluctuation amplitudes (AF_RPE; AF_CHE; AF_CREM) were compared between groups using nonparametric permutation. Regional amplitudes were compared using Mann-Whitney analysis and Cox survival analysis. Subject-specific pulsations were analyzed through Z-score mapping. AF_CREM and AF_RPE were significantly elevated across PCNSL brains, with lesser increases in AF_CHE. However, only significant increases in AF_RPE remained after correcting for sex and head displacement. AF_RPE showed a link to mortality as it was markedly elevated in deceased patients. While elevations in all pulsations were present within (peri)tumoral regions, AF_RPE elevations extended into extra-tumoral white matter and grey matter. Thus, altered cardiorespiratory fluctuations give rise to dysfunctional vasomotor and CSF pulsations in PCNSL, predicting impaired glymphatic function.