Toward accurate cerebral blood flow estimation in mice after accounting for anesthesia

Zhiliang Wei; Yuguo Li; Adnan Bibic; Wenzhen Duan; Jiadi Xu; Hanzhang Lu

doi:10.3389/fphys.2023.1169622

Toward accurate cerebral blood flow estimation in mice after accounting for anesthesia

Front Physiol. 2023 Apr 12:14:1169622. doi: 10.3389/fphys.2023.1169622. eCollection 2023.

Authors

Zhiliang Wei^{1

2}, Yuguo Li^{1

2}, Adnan Bibic², Wenzhen Duan^{3

4}, Jiadi Xu^{1

2}, Hanzhang Lu^{1

2

5}

Affiliations

¹ Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
² F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States.
³ Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁴ The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
⁵ Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Abstract

Purpose: To improve the accuracy of cerebral blood flow (CBF) measurement in mice by accounting for the anesthesia effects. Methods: The dependence of CBF on anesthesia dose and time was investigated by simultaneously measuring respiration rate (RR) and heart rate (HR) under four different anesthetic regimens. Quantitative CBF was measured by a phase-contrast (PC) MRI technique. RR was evaluated with a mouse monitoring system (MouseOX) while HR was determined using an ultrashort-TE MRI sequence. CBF, RR, and HR were recorded dynamically with a temporal resolution of 1 min in a total of 19 mice. Linear regression models were used to investigate the relationships among CBF, anesthesia dose, RR, and HR. Results: CBF, RR, and HR all showed a significant dependence on anesthesia dose (p < 0.0001). However, the dose in itself was insufficient to account for the variations in physiological parameters, in that they showed a time-dependent change even for a constant dose. RR and HR together can explain 52.6% of the variations in CBF measurements, which is greater than the amount of variance explained by anesthesia dose (32.4%). Based on the multi-parametric regression results, a model was proposed to correct the anesthesia effects in mouse CBF measurements, specifically ${C B F}_{c o r r e c t e d} = C B F + 0.58 R R - 0.41 H R - 32.66 D o s e$ . We also reported awake-state CBF in mice to be 142.0 ± 8.8 mL/100 g/min, which is consistent with the model-predicted value. Conclusion: The accuracy of CBF measurement in mice can be improved by using a correction model that accounts for respiration rate, heart rate, and anesthesia dose.

Keywords: MRI; cerebral blood flow (CBF); dose; heart rate (HR); isoflurane; mouse; phase contrast (PC); respiration rate (RR).

Abstract

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