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

Abstract

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.

Whole brain optoacoustic tomography reveals strain-specific regional beta-amyloid densities in Alzheimer’s disease amyloidosis models

“…Registration between MSOT and MRI/atlas can additionally boost the performance of these models and further provide a better anatomical reference for regional analysis. Automatic registration methods have been established for 2D dataset 55, 56 , which can potentially be adapted to 3D vMSOT datasets. However, as both arcAβ and APP/PS1 mice showed amyloid deposits in the cerebellum at an old age, regions typically considered as reference region, we therefore opted for average absorbance retention (60-120 min) rather than the reference tissue region modelling.…”

Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy

“…In addition, the LMI imaging approach is optimally suited for imaging large objects up to a centimeter scale, which is not attainable with multi-photon microscopy methods that are further hindered by the lack of optimal labels with large absorption cross section and longer absorption/emission wavelengths. Thus, the set-up is ideally suited to detect immunological and vascular events in the mouse brain using dedicated probes [47][48][49].…”

Automated registration of magnetic resonance imaging and optoacoustic tomography data for experimental studies

“…The application of affine transformation has been shown to yield robust results for the registration of rodent brain images acquired using OAT and MRI. 11,13,18 In addition, a one-plus-one evolutionary optimization algorithm was applied to search for the transformation parameters. The final parameters for the transformation are generated by iteratively perturbing or mutating the parameters from the last iteration (the parent).…”

“…OAT is particularly attractive for (neuro)imaging of rodents as it combines the sensitivity and tissue coverage of optical imaging with high spatial resolution provided by ultrasound, [5][6][7][8][9] enabling versatile applications. For example, OAT allows studying cerebral hemodynamics, 3 neural activity based on calcium activity, 10 activity of enzymes such as metalloproteinase, 11 or blood brain barrier integrity 12 in animal models in vivo. Similarly, the method yields phenotypic readouts of pathology, such as the deposition of amyloid beta in murine models of Alzheimer's disease 13 or hypoxia in experimental glioblastoma.…”

“…Moreover, properly registered multimodal imaging data allow obtaining structural, physiological, and molecular information from the same animal, increasing the scientific value of the investigation and reducing the number of animals needed for a study. The methods for registering OAT-MRI reported so far were all based on landmarks in the images, 11,[17][18][19] and hence depend largely on manual input. Unbiased automated registration of OAT data with MRI or other modalities is still lacking.…”