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Review of confounding effects on perfusion measurements

Patricia Clement1*, Henk-Jan Mutsaerts2, Eidrees Ghariq2, Marion Smits3, Marjan Acou1, Egill Rostrup4, Francesca Benedetta Pizzini5, Jorge Jovicich6, Mervi Könönen7, Ritva Vanninen7, António Bastos-Leite8, Roland Wiest9, Elna-Marie Larsson10 and Eric Achten1
  • 1 Ghent University, Belgium
  • 2 Leiden University Medical Center, Netherlands
  • 3 Erasmus MC, Netherlands
  • 4 University Copenhagen, Denmark
  • 5 University Hospital Verona, Italy
  • 6 University of Trento, Italy
  • 7 Kuopio University Hospital, Finland
  • 8 University Porto, Portugal
  • 9 University Hospital Bern, Switzerland
  • 10 Uppsala University, Sweden

PURPOSE Quantifying brain perfusion, with arterial spin labeling supplies important information on the pathophysiological state of the brain but is biased by a battery of confounding factors, such as patient characteristics, lifestyle and medication use. Standardization of measurement conditions and knowledge of the most important confounders is therefore essential for quantification and pattern recognition. In this review the impact of the majority of those confounding factors found in the literature on brain perfusion is summarized and a standard operating procedure to take all those effects into account is proposed. METHODS An extensive literature search was executed on probable confounding factors comprising solely human studies, using a variety of perfusion techniques such as Xe-CT, PET, SPECT, ASL, and even TCD. This information is used to build a database comprising all factors and their effects, and the formulation of a standard operation procedure to take the impact of those factors into account. RESULTS AND DISCUSSION In more than 650 articles information on the impact of over a hundred different confounding factors and medication groups were investigated. The vast majority of the reported confounding factors induce a significant effect on brain perfusion and in most cases this impact is consistent throughout the literature. On the other hand there are still plenty of factors which are subject to discussion as shown by contradictory results or lack of serious research, such as the effects of mood, IQ, education and BMI. One of the best studied and most remarkable findings is the influence of caffeine, which modulates global brain perfusion by 30%. For other confounding factors, like many psychotropic medications, not only global, but also regional perfusion changes are reported, compounding the reliability of pattern recognition in the analysis of perfusion measurements. Even though studying the impact of those physiological factors and taking them into account seems an intensive and nearly infeasible task due to the complexity of their effects, the importance of standardising this intersubject variability becomes clear when comparing this bias with the bias caused by technical confounds, such as labelling efficiency. In view of this standardisation, we compiled a standard operating procedure which will be made freely available. Both a questionnaire and measurements before and during perfusion scans, as well as guidelines for the researcher are included in this procedure. This standard operating procedure aims to map the intersubject variability which can be used to take those confounding factors into account in order to perform quantitative perfusion measurement. CONCLUSION This review underlines the importance of many physiological confounding factors of perfusion quantification and perfusion patterns in the brain. More than one hundred confounding factors are already intensively studied. To disentangle the effects of the most important confounders from effects from ageing and disease, we propose a standard operating procedure, containing a questionnaire, measurements and guidelines to standardize perfusion measurement. This review results from COST Action BM1103.

Keywords: cerebral perfusion, Arterial Spin Labeling, confounding factors, standard operating procedures, normalisation, pattern recognition, quantitative perfusion measurement

Conference: Belgian Brain Council 2014 MODULATING THE BRAIN: FACTS, FICTION, FUTURE, Ghent, Belgium, 4 Oct - 4 Oct, 2014.

Presentation Type: Oral Presentation

Topic: Clinical Neuroscience

Citation: Clement P, Mutsaerts H, Ghariq E, Smits M, Acou M, Rostrup E, Pizzini F, Jovicich J, Könönen M, Vanninen R, Bastos-Leite A, Wiest R, Larsson E and Achten E (2014). Review of confounding effects on perfusion measurements. Conference Abstract: Belgian Brain Council 2014 MODULATING THE BRAIN: FACTS, FICTION, FUTURE. doi: 10.3389/conf.fnhum.2014.214.00073

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Received: 14 Jul 2014; Published Online: 16 Aug 2014.

* Correspondence: Ms. Patricia Clement, Ghent University, Ghent, Belgium, patricia.clement@ugent.be