The most clinically compatible PAT configuration usually employs a linear ultrasound array, which often has a limited detection view and poor image fidelity. Exogenous contrast agents such as nanoparticles can be employed but lacks clinical translation potential. We have developed a new methodology by using clinically-approved microbubble as virtual point sources that strongly scatter the local pressure waves from surround hemoglobin, preserving PAT’s functional capability and clinical translation potential. We can overcome the limited-detection-view problem and achieve high-fidelity functional PAT in deep tissue. We have investigated the working principle and demonstrated proof-of-concept applications using simulations, phantoms, and in vivo small-animal studies.
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.
Our study exploits Rhodopseudomonas palustris BphP1 bacterial phytochrome to generate a near-infrared (NIR) loxP-BphP1 photoswitchable transgenic mouse model that enables deep-tissue optogenetics and photoacoustic tomography (PAT). BphP1 incorporates biliverdin and reversibly switches between the ground state and activated state, with distinct optical absorption spectra in the NIR window. We validated the optogenetic performance of the BphP1-encoded mouse model to trigger gene transcription, and demonstrated its superior capability of deep-tissue optogenetics. Then, taking advantage of BphP1's photoswitching properties, we can suppress the non-switching signals from background blood and improve the molecular detection sensitivity of PAT by three orders of magnitude.
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.
KEYWORDS: 3D modeling, Photoacoustic imaging, Autoregressive models, Visual process modeling, In vitro testing, Blood, 3D printing, Visualization, Photoacoustic microscopy, Digital Light Processing
Understanding thrombosis formation is necessary for developing safe and effective treatments. We fabricated sophisticated in vitro models of blood vessels with internal microchannels by using digital light processing-based 3D printing method. Photoacoustic microscopy (PAM) offers a useful platform for imaging 3D-printed vascular structures with different patterns of microchannels. Our results show that PAM can provide clear microchannel structures at depths up to 3.6 mm. We further quantified the blood oxygenation in the 3D-printed vascular models, showing that thrombi had much lower oxygenation than the normal blood. Integration of PAM with 3D printing/bioprinting will enable numerous applications in tissue engineering.
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