Noninvasive detection of acute cerebral hypoxia and subsequent matrix-metalloproteinase activity in a mouse model of cerebral ischemia using multispectral-optoacoustic-tomography.

Oxygen metabolism and matrix metalloproteinases (MMPs) play important roles in the pathophysiology of cerebral ischemia. Using multispectral optoacoustic tomography (MSOT) imaging, we visualized changes in cerebral tissue oxygenation during 1 h of transient middle cerebral artery occlusion (tMCAO) and at 48 h after reperfusion together with MMP activity using an MMP-activatable probe. The deoxyhemoglobin, oxyhemoglobin, and MMP signals were coregistered with structural magnetic resonance imaging data. The ipsi-/contralateral ratio of tissue oxygen saturation ([Formula: see text]) was significantly reduced during 1 h of tMCAO and recovered after 48 h of reperfusion in tMCAO compared with sham-operated mice ([Formula: see text] to 10 per group). A higher ipsi-/contralateral MMP signal ratio was detected at 48 h after reperfusion in the lesioned brain regions of tMCAO compared with the sham-operated animal ([Formula: see text] to 6 per group). near-infrared fluorescence imaging of MMP signal in brain slices was used to validate MSOT measurements. In conclusion, noninvasive MSOT imaging can provide visualization of hemodynamic alterations and MMP activity in a mouse model of cerebral ischemia.