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

Thomson, B. R.; Richter, H.; Akeret, K.; Buzzi, R. M.; Anagnostakou, V.; van Niftrik, B. H. B.; Schwendinger, N.; Kulcsar, Z.; Kronen, P. W.; Regli, L.; Fierstra, J.; Schaer, D. J.; Hugelshofer, M.

doi:10.1101/2022.04.05.487168

bioRxiv · 10.1101/2022.04.05.487168

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

Thomson, B. R.·Richter, H.·Akeret, K.·Buzzi, R. M.·Anagnostakou, V.·van Niftrik, B. H. B.·Schwendinger, N.·Kulcsar, Z.·Kronen, P. W.·Regli, L.·Fierstra, J.·Schaer, D. J.·Hugelshofer, M.

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Abstract

PurposeCell-free hemoglobin in the cerebrospinal fluid (CSF-Hb) may be one of the main drivers of secondary brain injury after aneurysmal subarachnoid hemorrhage. 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. MethodsDSA 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. ResultsDSA imaging did not show a difference in mean transit time or cerebral blood flow. Wholebrain 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). ConclusionIt 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.

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Thomson, B. R., Richter, H., Akeret, K., Buzzi, R. M., Anagnostakou, V., van Niftrik, B. H. B., Schwendinger, N., Kulcsar, Z., Kronen, P. W., Regli, L., Fierstra, J., Schaer, D. J., Hugelshofer, M.. 2022-04-07. Blood oxygenation-level dependent cerebrovascular reactivity imaging as strategy to monitor CSF-hemoglobin toxicity. https://doi.org/10.1101/2022.04.05.487168

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