University of Oulu

Poltojainen, V., Kemppainen, J., Keinänen, N., Bode, M., Isokangas, J.-M., Kuitunen, H., Nikkinen, J., Sonkajärvi, E., Korhonen, V., Tuovinen, T., Järvelä, M., Huotari, N., Raitamaa, L., Kananen, J., Korhonen, T., Tetri, S., Kuittinen, O., & Kiviniemi, V. (2022). Physiological instability is linked to mortality in primary central nervous system lymphoma: A case–control fMRI study. Human Brain Mapping, 43( 13), 4030– 4044.

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

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Author: Poltojainen, Valter1,2,3; Kemppainen, Janette1,4; Keinänen, Nina5;
Organizations: 1Oulu Functional Neuroimaging, University of Oulu/Oulu University Hospital, Oulu, Finland
2Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland
3Department of Radiology, Oulu University Hospital, Oulu, Finland
4Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
5Department of Anaesthesiology, Oulu University Hospital, Oulu, Finland
6Department of Oncology and Haematology, Oulu University Hospital, Oulu, Finland
7Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland
8Medical Research Center, University of Oulu/Oulu University Hospital, Oulu, Finland
9Department of Clinical Neuroscience, University of Oulu, Oulu, Finland
10Cancer Center, Kuopio University Hospital, Kuopio, Finland
11Faculty of Health Medicine, Institute of Clinical Medicine, University of Eastern Finland, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2023-06-27


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 (MREGBOLD) 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 MREGBOLD signal during 2018–2021. Motion effects were removed. Voxel-by-voxel Coefficient of Variation (CV) maps of MREGBOLD 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 × 10₅mm₃) extended spatially beyond FLAIR lesions (median 0.62 × 10₅mm₃) with differences in volumes (p = .0055).

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Series: Human brain mapping
ISSN: 1065-9471
ISSN-E: 1097-0193
ISSN-L: 1065-9471
Volume: 43
Issue: 13
Pages: 4030 - 4044
DOI: 10.1002/hbm.25901
Type of Publication: A1 Journal article – refereed
Field of Science: 3112 Neurosciences
Funding: Academy of Finland, Grant/Award Numbers: Project 338599, TERVA 314497, TERVA 335720; Instrumentarium Science Foundation (Janne Kananen); Jane ja Aatos Erkko Foundation; Maire Taponen Foundation (Janne Kananen); Medical Research Center Oulu (Janne Kananen); Orion Research Foundation (Janette Kemppainen); Finnish Brain Foundation (Janne Kananen); Finnish Medical Foundation (Janne Kananen, Timo Tuovinen, Janette Kemppainen).
Academy of Finland Grant Number: 338599
Detailed Information: 338599 (Academy of Finland Funding decision)
314497 (Academy of Finland Funding decision)
335720 (Academy of Finland Funding decision)
Copyright information: © 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.