David Y Chung1, Kazutaka Sugimoto2, Paul Fischer3, Maximilian Böhm3, Tsubasa Takizawa4, Homa Sadeghian5, Andreia Morais5, Andrea Harriott6, Fumiaki Oka2, Tao Qin5, Nils Henninger7, Mohammad A Yaseen8, Sava Sakadžić8, Cenk Ayata9. 1. Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Neurocritical Care and Emergency Neurology, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: dychung@mgh.harvard.edu. 2. Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Department of Neurosurgery, Yamaguchi University School of Medicine, Ube, Japan. 3. Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany. 4. Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Department of Neurology, Keio University School of Medicine, Tokyo, Japan. 5. Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA. 6. Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Stroke Service, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. 7. Departments of Neurology and Psychiatry, University of Massachusetts Medical School, Worcester, MA, USA. 8. Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA. 9. Neurovascular Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Stroke Service, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: cayata@mgh.harvard.edu.
Abstract
BACKGROUND: Cortical spreading depolarization (CSD) is a phenomenon classically associated with migraine aura. CSDs have also been implicated in secondary injury following ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury; however, most investigations involving these disease processes do not account for the occurrence of CSDs. A major barrier to detection of CSDs in experimental models is that currently validated methods are invasive and require specialized equipment and a high level of expertise to implement. NEW METHOD: We present a low-cost, easy-to-implement approach to the detection of CSDs in the mouse through full-thickness intact skull. Our method uses the optical intrinsic signal from white light illumination (OIS-WL) and allows for real-time in vivo detection of CSDs using readily available USB cameras. RESULTS: OIS-WL detected 100% of CSDs that were seen with simultaneous electrode recording (69 CSDs in 28 mice), laser Doppler flowmetry (82 CSDs in 10 mice), laser speckle flowmetry (68 CSDs in 25 mice), or combined electrode recording plus laser speckle flowmetry (29 CSDs in 20 mice). OIS-WL detected 1 additional CSD that was missed by laser Doppler flowmetry. COMPARISON WITH EXISTING METHODS: OIS-WL is less invasive than electrophysiological recordings and easier to implement than laser speckle flowmetry. Moreover, it provides excellent spatial and temporal resolution for dynamic imaging of CSDs in the setting of brain injury. CONCLUSIONS: Detection of CSDs with an inexpensive USB camera and white light source provides a reliable method for the in vivo and non-invasive detection of CSDs through unaltered mouse skull.
BACKGROUND: Cortical spreading depolarization (CSD) is a phenomenon classically associated with migraine aura. CSDs have also been implicated in secondary injury following ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and traumatic brain injury; however, most investigations involving these disease processes do not account for the occurrence of CSDs. A major barrier to detection of CSDs in experimental models is that currently validated methods are invasive and require specialized equipment and a high level of expertise to implement. NEW METHOD: We present a low-cost, easy-to-implement approach to the detection of CSDs in the mouse through full-thickness intact skull. Our method uses the optical intrinsic signal from white light illumination (OIS-WL) and allows for real-time in vivo detection of CSDs using readily available USB cameras. RESULTS: OIS-WL detected 100% of CSDs that were seen with simultaneous electrode recording (69 CSDs in 28 mice), laser Doppler flowmetry (82 CSDs in 10 mice), laser speckle flowmetry (68 CSDs in 25 mice), or combined electrode recording plus laser speckle flowmetry (29 CSDs in 20 mice). OIS-WL detected 1 additional CSD that was missed by laser Doppler flowmetry. COMPARISON WITH EXISTING METHODS: OIS-WL is less invasive than electrophysiological recordings and easier to implement than laser speckle flowmetry. Moreover, it provides excellent spatial and temporal resolution for dynamic imaging of CSDs in the setting of brain injury. CONCLUSIONS: Detection of CSDs with an inexpensive USB camera and white light source provides a reliable method for the in vivo and non-invasive detection of CSDs through unaltered mouse skull.
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