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.
Photoacoustic (PA) tomography (PAT) is a promising technology for noninvasive temperature sensing. However, traditional PA thermometry can measure only the temperature changes relative to a baseline. Here we report a new thermal-energy-memory-based PA thermometry (TEMPT) to quantify the Grüneisen parameter and recover the absolute temperature distribution in deep tissues. We have validated the feasibility of TEMPT on tissue-mimicking phantoms and achieved a measurement accuracy of ~0.5 °C at 1.5 cm depth. As proof-of-concept, we applied TEMPT for temperature mapping during focused ultrasound treatment in mice in vivo. TEMPT is expected to find applications in thermotherapy on small animal models.
We report a photoacoustic computed tomography (PACT) system using a customized optical fiber with a cylindrical diffuser to internally illuminate deep targets. The traditional external light illumination in PACT usually limits the penetration depth to a few centimeters from the tissue surface, mainly due to strong optical attenuation along the light propagation path from the outside in. By contrast, internal light illumination, with external ultrasound detection, can potentially detect much deeper targets. Different from previous internal illumination PACT implementations using forward-looking optical fibers, our internal-illumination PACT system uses a customized optical fiber with a 3-cm-long conoid needle diffuser attached to the fiber tip, which can homogeneously illuminate the surrounding space and substantially enlarge the field of view. We characterized the internal illumination distribution and PACT system performance. We performed tissue phantom and in vivo animal studies to further demonstrate the superior imaging depth using internal illumination over external illumination. We imaged a 7.5-cm-deep leaf target embedded in optically scattering medium and the beating heart of a mouse overlaid with 3.7-cm-thick chicken tissue. Our results have collectively demonstrated that the internal light illumination combined with external ultrasound detection might be a useful strategy to improve the penetration depth of PACT in imaging deep organs of large animals and humans.
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