Mapping of neuroinflammation-induced hypoxia in the spinal cord using optoacoustic imaging

Recent studies suggest that metabolic changes and oxygen deficiency in the central nervous system play an important role in the pathophysiology of multiple sclerosis (MS). In our present study, we investigated the changes in oxygenation and analyzed the vascular perfusion of the spinal cord in a rodent model of MS. We performed multispectral optoacoustic tomography of the lumbar spinal cord before and after an oxygen enhancement challenge in mice with experimental autoimmune encephalomyelitis (EAE), a model for MS. In addition, mice were transcardially perfused with lectin to label the vasculature and their spinal columns were optically cleared, followed by light sheet fluorescence microscopy. To analyze the angioarchitecture of the intact spine, we used VesSAP, a novel deep learning-based framework. In EAE mice, the spinal cord had lower oxygen saturation and hemoglobin concentration compared to healthy mice, indicating compromised perfusion of the spinal cord. Oxygen administration reversed hypoxia in the spinal cord of EAE mice, although the ventral region remained hypoxic. Additionally, despite the increased vascular density, we report a reduction in length and complexity of the perfused vascular network in EAE. Taken together, these findings highlight a new aspect of neuroinflammatory pathology, revealing a significant degree of hypoxia in EAE in vivo that is accompanied by changes in spinal vascular perfusion. The study also introduces optoacoustic imaging as a tractable technique with the potential to further decipher the role of hypoxia in EAE and to monitor it in MS patients.

Automated summary

Recent studies have revealed that metabolic changes and oxygen deficiency in the central nervous system are important factors in the development of multiple sclerosis (MS). In this study, researchers investigated the changes in oxygenation and blood flow in the spinal cord of a mouse model of MS. They used multispectral optoacoustic tomography to analyze the spinal cord before and after oxygen administration in mice with experimental autoimmune encephalomyelitis (EAE), a model for MS. Additionally, they utilized a novel deep learning-based framework called VesSAP to analyze the vascular structure of the intact spine. The study found that EAE mice had lower oxygen saturation and hemoglobin concentration in the spinal cord, indicating compromised blood flow. However, oxygen administration improved the hypoxic condition in the spinal cord, although the ventral region remained hypoxic. Despite increased vascular density, the researchers observed a reduction in the length and complexity of the perfused vascular network in EAE. Overall, these findings highlight the importance of considering hypoxia and spinal vascular perfusion in the neuroinflammatory pathology of EAE and MS. The study also introduces optoacoustic imaging as a potential technique for further understanding the role of hypoxia in EAE and monitoring it in MS patients.