Imaging increased metabolism in the spinal cord in mice after middle cerebral artery occlusion

Ruiqing Ni; Nadja Straumann; Serana Fazio; Xose Luis Dean-Ben; Georgios Louloudis; Claudia Keller; Daniel Razansky; Simon Ametamey; Linjing Mu; César Nombela-Arrieta; Jan Klohs

doi:10.1016/j.pacs.2023.100532

Imaging increased metabolism in the spinal cord in mice after middle cerebral artery occlusion

Photoacoustics. 2023 Jul 15:32:100532. doi: 10.1016/j.pacs.2023.100532. eCollection 2023 Aug.

Authors

Ruiqing Ni^{1

2

3}, Nadja Straumann¹, Serana Fazio⁴, Xose Luis Dean-Ben², Georgios Louloudis², Claudia Keller⁵, Daniel Razansky^{2

3}, Simon Ametamey⁵, Linjing Mu⁵, César Nombela-Arrieta⁴, Jan Klohs²

Affiliations

¹ Institute for Regenerative Medicine, University of Zurich, Zurich, Switzerland.
² Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland.
³ Zentrum für Neurowissenschaften Zurich, Zurich, Switzerland.
⁴ Department of Medical Oncology and Hematology, University and University Hospital Zurich, Zurich, Switzerland.
⁵ Center for Radiopharmaceutical Sciences ETH, PSI and USZ, Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland.

Abstract

Emerging evidence indicates crosstalk between the brain and hematopoietic system following cerebral ischemia. Here, we investigated metabolism and oxygenation in the spleen and spinal cord in a transient middle cerebral artery occlusion (tMCAO) model. Sham-operated and tMCAO mice underwent [¹⁸F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) to assess glucose metabolism. Naïve, sham-operated and tMCAO mice underwent multispectral optoacoustic tomography (MSOT) assisted by quantitative model-based reconstruction and unmixing algorithms for accurate mapping of oxygenation patterns in peripheral tissues at 24 h after reperfusion. We found increased [¹⁸F]FDG uptake and reduced MSOT oxygen saturation, indicating hypoxia in the thoracic spinal cord of tMCAO mice compared with sham-operated mice but not in the spleen. Reduced spleen size was observed in tMCAO mice compared with sham-operated mice ex vivo. tMCAO led to an increase in the numbers of mature T cells in femoral bone marrow tissues, concomitant with a stark reduction in these cell subsets in the spleen and peripheral blood. The combination of quantitative PET and MSOT thus enabled observation of hypoxia and increased metabolic activity in the spinal cord of tMCAO mice at 24 h after occlusion compared to sham-operated mice.

Keywords: Ischemic stroke; MSOT; Metabolism; Optoacoustic tomography; Oxygenation; Positron emission tomography; Spinal cord; Spleen; fluorodeoxyglucose (FDG).