title: Studying cerebral hemodynamics and metabolism using simultaneous near-infrared spectroscopy and transcranial Doppler ultrasound: a hyperventilation and caffeine study.
abstract: Caffeine is one of the most widely consumed psycho-stimulants in the world, yet little is known about its effects on brain oxygenation and metabolism. Using a double-blind, placebo-controlled, randomized cross-over study design, we combined transcranial Doppler ultrasound (TCD) and near-infrared spectroscopy (NIRS) to study caffeine's effect on middle cerebral artery peak blood flow velocity (Vp), brain tissue oxygenation (StO2), total hemoglobin (tHb), and cerebral oxygen metabolism (CMRO2) in five subjects. Hyperventilation-induced hypocapnia served as a control to verify the sensitivity of our measurements. During hypocapnia (~16 mmHg below resting values), Vp decreased by 40.0 ± 2.4% (95% CI, P < 0.001), while StO2 and tHb decreased by 2.9 ± 0.3% and 2.6 ± 0.4%, respectively (P = 0.003 and P = 0.002, respectively). CMRO2, calculated using the Fick equation, was reduced by 29.3 ± 9% compared to the isocapnic-euoxia baseline (P < 0.001). In the pharmacological experiments, there was a significant decrease in Vp, StO2, and tHb after ingestion of 200 mg of caffeine compared with placebo. There was no significant difference in CMRO2 between caffeine and placebo. Both showed a CMRO2 decline compared to baseline showing the importance of a placebo control. In conclusion, this study showed that profound hypocapnia impairs cerebral oxidative metabolism. We provide new insight into the effects of caffeine on cerebral hemodynamics. Moreover, this study showed that multimodal NIRS/TCD is an excellent tool for studying brain hemodynamic responses to pharmacological interventions and physiological challenges.
authors.affiliation: Department of Radiology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada Faculty of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Runze
authors.initials: R
authors.lastname: Yang
authors.affiliation: Faculty of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Brugniaux
authors.affiliation: Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Harinder
authors.initials: H
authors.lastname: Dhaliwal
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Beaudin
authors.affiliation: Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Misha
authors.initials: M
authors.lastname: Eliasziw
authors.affiliation: Faculty of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada Libin Cardiovascular Institute of Alberta, Calgary, Alberta, Canada.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Poulin
authors.affiliation: Department of Radiology, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada Faculty of Medicine, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada dunnj@ucalgary.ca.
authors.forename: Jeff F
authors.initials: JF
authors.lastname: Dunn
keywords: Brain; near‐infrared spectroscopy; transcranial Doppler ultrasound