Physiological instability is linked to mortality in primary central nervous system lymphoma: A case-control fMRI study

Valter Poltojainen; Janette Kemppainen; Nina Keinänen; Michaela Bode; Juha-Matti Isokangas; Hanne Kuitunen; Juha Nikkinen; Eila Sonkajärvi; Vesa Korhonen; Timo Tuovinen; Matti Järvelä; Niko Huotari; Lauri Raitamaa; Janne Kananen; Tommi Korhonen; Sami Tetri; Outi Kuittinen; Vesa Kiviniemi

doi:10.1002/hbm.25901

Physiological instability is linked to mortality in primary central nervous system lymphoma: A case-control fMRI study

Hum Brain Mapp. 2022 Sep;43(13):4030-4044. doi: 10.1002/hbm.25901. Epub 2022 May 11.

Authors

Valter Poltojainen^{1

2

3}, Janette Kemppainen^{1

4}, Nina Keinänen⁵, Michaela Bode^{2

3}, Juha-Matti Isokangas³, Hanne Kuitunen⁶, Juha Nikkinen^{2

7}, Eila Sonkajärvi⁵, Vesa Korhonen^{1

2

3}, Timo Tuovinen^{1

2

3}, Matti Järvelä^{1

2

3}, Niko Huotari^{1

2

3}, Lauri Raitamaa^{1

2

3}, Janne Kananen^{1

2

3}, Tommi Korhonen^{8

9}, Sami Tetri^{8

9}, Outi Kuittinen^{6

10

11}, Vesa Kiviniemi^{1

2

3}

Affiliations

¹ Oulu Functional Neuroimaging, University of Oulu/Oulu University Hospital, Oulu, Finland.
² Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland.
³ Department of Radiology, Oulu University Hospital, Oulu, Finland.
⁴ Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland.
⁵ Department of Anaesthesiology, Oulu University Hospital, Oulu, Finland.
⁶ Department of Oncology and Haematology, Oulu University Hospital, Oulu, Finland.
⁷ Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland.
⁸ Medical Research Center, University of Oulu/Oulu University Hospital, Oulu, Finland.
⁹ Department of Clinical Neuroscience, University of Oulu, Oulu, Finland.
¹⁰ Cancer Center, Kuopio University Hospital, Kuopio, Finland.
¹¹ Faculty of Health Medicine, Institute of Clinical Medicine, University of Eastern Finland, Oulu, Finland.

Abstract

Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREG_BOLD ) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age-matched controls (median 63y; 73% females) were scanned for MREG_BOLD signal during 2018-2021. Motion effects were removed. Voxel-by-voxel Coefficient of Variation (CV) maps of MREG_BOLD signal was calculated to examine the stability of physiological brain pulsations. Group-level differences in CV were examined using nonparametric covariate-adjusted tests. Subject-level CV alterations were examined against control population Z-score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast-enhanced, diffusion-weighted, fluid-attenuated inversion recovery (FLAIR) data]. Whole-brain mean CV was linked to short-term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 10⁵ mm³ ) extended spatially beyond FLAIR lesions (median 0.62 × 10⁵ mm³ ) with differences in volumes (p = .0055).

Keywords: brain pulsation; functional imaging; lymphoma; malignancy; mortality.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / diagnostic imaging
Case-Control Studies
Female
Humans
Lymphoma* / diagnostic imaging
Magnetic Resonance Imaging* / methods
Male
Neuroimaging / methods