Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity

Bart R Thomson; Henning Richter; Kevin Akeret; Raphael M Buzzi; Vania Anagnostakou; Christiaan H B van Niftrik; Nina Schwendinger; Zsolt Kulcsar; Peter W Kronen; Luca Regli; Jorn Fierstra; Dominik J Schaer; Michael Hugelshofer

doi:10.1016/j.jstrokecerebrovasdis.2023.106985

Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity

J Stroke Cerebrovasc Dis. 2023 Mar;32(3):106985. doi: 10.1016/j.jstrokecerebrovasdis.2023.106985. Epub 2023 Jan 12.

Affiliations

¹ Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland; Division of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland.
² Clinic for Diagnostic Imaging, Department of Clinical Diagnostics and Services, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Center for Applied Biotechnology and Molecular Medicine (CABMM), University of Zurich, Zurich, Switzerland.
³ Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
⁴ Division of Internal Medicine, University Hospital of Zurich, Zurich, Switzerland.
⁵ Department of Neuroradiology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland; Department of Radiology, University of Massachusetts Medical School, Worcester, MA, USA.
⁶ Center for Applied Biotechnology and Molecular Medicine (CABMM), University of Zurich, Zurich, Switzerland; Department of Neuroradiology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
⁷ Center for Applied Biotechnology and Molecular Medicine (CABMM), University of Zurich, Zurich, Switzerland; Veterinary Anaesthesia Services - International, Winterthur, Switzerland.
⁸ Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland; Center for Applied Biotechnology and Molecular Medicine (CABMM), University of Zurich, Zurich, Switzerland. Electronic address: michael.hugelshofer@usz.ch.

PMID: 36640721
DOI: 10.1016/j.jstrokecerebrovasdis.2023.106985

Abstract

Objectives: Cell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage (aSAH). Haptoglobin scavenging of CSF-Hb has been shown to mitigate cerebrovascular disruption. Using digital subtraction angiography (DSA) and blood oxygenation-level dependent cerebrovascular reactivity imaging (BOLD-CVR) the aim was to assess the acute toxic effect of CSF-Hb on cerebral blood flow and autoregulation, as well as to test the protective effects of haptoglobin.

Methods: DSA imaging was performed in eight anesthetized and ventilated sheep (mean weight: 80.4 kg) at baseline, 15, 30, 45 and 60 minutes after infusion of hemoglobin (Hb) or co-infusion with haptoglobin (Hb:Haptoglobin) into the left lateral ventricle. Additionally, 10 ventilated sheep (mean weight: 79.8 kg) underwent BOLD-CVR imaging to assess the cerebrovascular reserve capacity.

Results: DSA imaging did not show a difference in mean transit time or cerebral blood flow. Whole-brain BOLD-CVR compared to baseline decreased more in the Hb group after 15 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs -0.01 ± 0.02) and remained diminished compared to Hb:Haptoglobin group after 30 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.0 ± 0.01), 45 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.01 vs 0.01 ± 0.02) and 60 minutes (Hb vs Hb:Haptoglobin: -0.03 ± 0.02 vs 0.01 ± 0.01).

Conclusion: It is demonstrated that CSF-Hb toxicity leads to rapid cerebrovascular reactivity impairment, which is blunted by haptoglobin co-infusion. BOLD-CVR may therefore be further evaluated as a monitoring strategy for CSF-Hb toxicity after aSAH.

Keywords: BOLD-CVR; CSF-Hb; Early detection; Imaging.

MeSH terms

Animals
Brain / diagnostic imaging
Cerebrovascular Circulation / physiology
Diagnostic Imaging
Haptoglobins*
Hemoglobins
Magnetic Resonance Imaging / methods
Sheep
Subarachnoid Hemorrhage* / diagnostic imaging

Substances

Haptoglobins
Hemoglobins