We present an experimental ischemic stroke study using our newly-developed multimodal imaging system that integrates photoacoustic computed tomography (PACT), high-frequency ultrasound imaging, and acoustic angiographic tomography, or PAUSAT. PAUSAT is capable of three-dimensional high-frequency ultrasound imaging of the brain morphology, micro-bubble-enabled acoustic angiography of the brain blood perfusion, and multispectral PACT of brain blood oxygenation. PAUSAT was able to clearly show the brain vascular changes after ischemic stroke, including significantly reduced blood perfusion and oxygenation. Using PAUSAT, stroke infarct volume was reliably measured. The PAUSAT results were confirmed by laser speckle imaging and histology.
KEYWORDS: Photoacoustic spectroscopy, Photoacoustic tomography, Acquisition tracking and pointing, Switching, Signal detection, Tissues, Color, Temperature metrology, In vivo imaging, Absorption
SignificanceBased 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.AimPrevious work has demonstrated that reversible color-shifting can drastically improve the detection sensitivity of PAT by suppressing nonswitching background signals. We aim to develop a new color switching-based PAT method using reversibly switchable thermochromics (ReST).ApproachWe developed a family of ReST with excellent water dispersion, biostability, and temperature-controlled color changes by surface modification of commercial thermochromic microcapsules with the hydrophilic polysaccharide alginate.ResultsThe optical absorbance of the ReST was switched on and off repeatedly by modulating the surrounding temperature, allowing differential photoacoustic detection that effectively suppressed the nonswitching background signal and substantially improved image contrast and detection sensitivity. We demonstrate reversible thermal-switching imaging of ReST in vitro and in vivo using three PAT modes at different length scales.ConclusionsReST-enabled PAT is a promising technology for high-sensitivity deep tissue imaging of molecular activity in temperature-related biomedical applications, such as cancer thermotherapy.
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