The Regulation of Vasomotor and Cardiorespiratory Pulsations Is Disrupted in Primary Central Nervous System Lymphoma: A Case-Control fMRI Study.

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 sequence. Respective MREG fluctuation amplitudes (AF; AF; AF) 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 and AF were significantly elevated across PCNSL brains, with lesser increases in AF. However, only significant increases in AF remained after correcting for sex and head displacement. AF 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 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.