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Integrated Photoacoustic, Ultrasound, and Angiographic Tomography (PAUSAT) for NonInvasive Whole-Brain Imaging of Ischemic Stroke

Presented here is an experimental ischemic stroke study using our newly developed noninvasive imaging system that integrates three acoustic-based imaging ...

Acoustically detecting the optical absorption contrast, photoacoustic imaging (PAI) is a highly versatile imaging modality that can provide anatomical, functional, molecular, and metabolic information of biological tissues. PAI is highly scalable and can probe the same biological process at various length scales ranging from single cells (microscopic) to the whole organ (macroscopic). Using hemoglobin as the endogenous contrast, PAI is capable of label-free imaging of blood vessels in the brain and mapping hemodynamic functions such as blood oxygenation and blood flow. These imaging merits make PAI a great tool for studying ischemic stroke, particularly for probing into hemodynamic changes and impaired cerebral blood perfusion as a consequence of stroke. In this narrative review, we aim to summarize the scientific progresses in the past decade by using PAI to monitor cerebral blood vessel impairment and restoration after ischemic stroke, mostly in the preclinical setting. We also outline and discuss the major technological barriers and challenges that need to be overcome so that PAI can play a more significant role in preclinical stroke research, and more importantly, accelerate its translation to be a useful clinical diagnosis and management tool for human strokes.

Sound out the impaired perfusion: Photoacoustic imaging in preclinical ischemic stroke.

We present an ischemic stroke study using our newly-developed PAUSAT system that integrates photoacoustic computed tomography (PACT), high-frequency ultrasound imaging, and acoustic angiographic tomography. PAUSAT is capable of three-dimensional (3D) imaging of the brain morphology, blood perfusion, and blood oxygenation. Using PAUSAT, we studied the hemodynamic changes in the whole mouse brain induced by two common ischemic stroke models: the permanent middle cerebral artery occlusion (pMCAO) model and the photothrombotic (PT) model. We imaged the same mouse brains before and after stroke, and quantitatively compared the two stroke models. We observed clear hemodynamic changes after ischemic stroke, including reduced blood perfusion and oxygenation. Such changes were spatially heterogenous. We also quantified the tissue infarct volume in both stroke models. The PAUSAT measurements were validated by laser speckle imaging and histology. Our results have collectively demonstrated that PAUSAT can be a valuable tool for non-invasive longitudinal studies of neurological diseases at the whole-brain scale.

Three-dimensional non-invasive brain imaging of ischemic stroke by integrated photoacoustic, ultrasound and angiographic tomography (PAUSAT).

Based on acoustic detection of optical absorption, photoacoustic tomography (PAT) allows functional and molecular imaging beyond the optical diffusion limit with high spatial resolution. However, multispectral functional and molecular PAT is often limited by decreased spectroscopic accuracy and reduced detection sensitivity in deep tissues, mainly due to wavelength-dependent optical attenuation and inaccurate acoustic inversion.

Multiscale photoacoustic tomography using reversibly switchable thermochromics.

Nanoparticle-based platforms are gaining strong interest in plant biology and bioenergy research to monitor and control biological processes in whole plants. However,  monitoring of biomolecules using nanoparticles inside plant cells remains challenging due to the impenetrability of the plant cell wall to nanoparticles beyond the exclusion limits (5-20 nm). To overcome this physical barrier, we have designed unique bimetallic silver-coated gold nanorods (AuNR@Ag) capable of entering plant cells, while conserving key plasmonic properties in the near-infrared (NIR). To demonstrate cellular internalization and tracking of the nanorods inside plant tissue, we used a comprehensive multimodal imaging approach that included transmission electron microscopy (TEM), confocal fluorescence microscopy, two-photon luminescence (TPL), X-ray fluorescence microscopy (XRF), and photoacoustics imaging (PAI). We successfully acquired SERS signals of nanorods  inside plant cells of tobacco leaves. On the same leaf samples, we applied orthogonal imaging methods, TPL and PAI techniques for  imaging of the nanorods. This study first demonstrates the intracellular internalization of AuNR@Ag inside whole plant systems for  SERS analysis in tobacco cells. This work demonstrates the potential of this nanoplatform as a new nanotool for intracellular  biosensing for plant biology.

Article	Year
Sound out the impaired perfusion: Photoacoustic imaging in preclinical ischemic stroke. Frontiers in neuroscience\| PubMed ID: 36532279	2022
Three-dimensional non-invasive brain imaging of ischemic stroke by integrated photoacoustic, ultrasound and angiographic tomography (PAUSAT). Photoacoustics\| PubMed ID: 36620854	2023
Multiscale photoacoustic tomography using reversibly switchable thermochromics. Journal of biomedical optics\| PubMed ID: 36817549	2023
Plasmonic nanorod probes' journey inside plant cells for SERS sensing and multimodal imaging. Nanoscale\| PubMed ID: 36924128	2023

Luca Menozzi

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