While lasers have been commonly used as illumination sources in photoacoustic (PA) imaging, their high purchase and maintenance costs, as well as their bulkiness, have hindered the rapid clinical dissemination of PA imaging. With this in mind, we explore an alternative illumination source for PA tomography—a xenon flash lamp with high pulse energy and a microsecond pulse width. We demonstrate that, by using a single xenon flash lamp, we can image both a black latex cord placed in chicken breast tissue at a depth of up to 3.5 cm ex vivo and an entire mouse body in vivo. Our findings indicate that the xenon flash lamp, producing optical illumination that is safe for humans, can be potentially applied to human tissue imaging.
Micro- and nanorobots excel in navigating the intricate and often inaccessible areas of the human body, offering immense potential for applications such as disease diagnosis, precision drug delivery, detoxification, and minimally invasive surgery. Despite their promise, practical deployment faces hurdles, including achieving stable propulsion in complex in vivo biological environments, real-time imaging and localization through deep tissue, and precise remote control for targeted therapy and ensuring high therapeutic efficacy. To overcome these obstacles, we introduce a hydrogel-based, imaging-guided, bioresorbable acoustic microrobot (BAM) designed to navigate the human body with high stability. Constructed using two-photon polymerization, a BAM comprises magnetic nanoparticles and therapeutic agents integrated into its hydrogel matrix for precision control and drug delivery. The microrobot features an optimized surface chemistry with a hydrophobic inner layer to substantially enhance microbubble retention in biofluids with multiday functionality and a hydrophilic outer layer to minimize aggregation and promote timely degradation. The dual-opening bubble-trapping cavity design enables a BAM to maintain consistent and efficient acoustic propulsion across a range of biological fluids. Under focused ultrasound stimulation, the entrapped microbubbles oscillate and enhance the contrast for real-time ultrasound imaging, facilitating precise tracking and control of BAM movement through wireless magnetic navigation. Moreover, the hydrolysis-driven biodegradability of BAMs ensures its safe dissolution after treatment, posing no risk of long-term residual harm. Thorough in vitro and in vivo experimental evidence demonstrates the promising capabilities of BAMs in biomedical applications. This approach shows promise for advancing minimally invasive medical interventions and targeted therapeutic delivery.
Metastasis is responsible for as many as 90% of cancer-related deaths, and the deadliest skin cancer, melanoma, has a high propensity for metastasis. Since hematogenous spread of circulating tumor cells (CTCs) is cancer's main route of metastasis, detecting and destroying CTCs can impede metastasis and improve patients' prognoses. Extensive studies employing exogenous agents to detect tumor-specific biomarkers and guide therapeutics to CTCs have achieved promising results, but biosafety remains a critical concern. Taking another approach, physical detection and destruction of CTCs is a safer way to evaluate and reduce metastasis risks. Melanoma cells strongly express melanosomes, providing a striking absorption contrast with the blood background in the red to near-infrared spectrum. Exploiting this intrinsic optical absorption contrast of circulating melanoma cells, we coupled dual-wavelength photoacoustic flow cytography with a nanosecond-pulsed laser killing mechanism that specifically targets melanoma CTCs. We have successfully achieved in vivo label-free imaging of rare single CTCs and CTC clusters in mice. Further, the photoacoustic signal from a CTC immediately hardware-triggers a lethal pinpoint laser irradiation that lyses it on the spot in a thermally confined manner. Our technology can facilitate early inhibition of metastasis by clearing circulating tumor cells from vasculature.
Capitalizing on endogenous hemoglobin contrast, photoacoustic computed tomography (PACT), a deep-tissue highresolution imaging modality, has drawn increasing interest in neuro-imaging. However, most existing studies are limited to functional imaging on the cortical surface, and the deep-brain structural imaging capability of PACT has never been demonstrated. Here, we explicitly studied the limiting factors of deep-brain PACT imaging. We found that the skull distorted the acoustic signal and blood suppressed the structural contrast from other chromophores. When the two effects are mitigated, PACT can provide high-resolution label-free structural imaging through the entire mouse brain. With 100 μm in-plane resolution, we can clearly identify major structures of the brain, and the image quality is comparable to that of magnetic resonance microscopy. Spectral PACT studies indicate that structural contrasts mainly originate from cytochrome and lipid. The feasibility of imaging the structure of the brain in vivo has also been discussed. Our results demonstrate that PACT is a promising modality for both structural and functional brain imaging.
We propose using noninvasive longitudinal optical-resolution photoacoustic microscopy (L-ORPAM) to quantify blood flow flux, oxygen saturation (sO2), and thereby the metabolic rate of oxygen (MRO2), for a renal tumor model in the same mouse over weeks to months. Experiments showed that the sO2 difference between the artery and vein decreased greatly due to the arteriovenous shunting effect during tumor growth. Moreover, hypermetabolism was exhibited by an increase in MRO2.
We have enhanced photoacoustic computed tomography with dry acoustic coupling that eliminates water immersion anxiety and wrinkling of the animal and facilitates incorporating complementary modalities and procedures. The dry acoustic coupler is made of a tubular elastic membrane enclosed by a closed transparent water tank. The tubular membrane ensures water-free contact with the animal, and the closed water tank allows pressurization for animal stabilization. The dry coupler was tested using a whole-body small-animal ring-shaped photoacoustic computed tomography system. Dry coupling was found to provide image quality comparable to that of conventional water coupling.
Dual Energy Computed Tomography (DECT) has recently gained significantly research interest because of its ability of object separation, contrast enhancement, artifact reduction and material composition assessment. Aiming for the nonlinear projection decomposition problem in DECT image reconstruction, a hybrid projection decomposition algorithm is proposed with combination of iterative method and isotransmission fitting method. Firstly, the nonlinear projection aquation for a given polychromatic projection value is transformed to linear equation plus a nonlinear pertubative item for single variable to speed up the iteration speed and avoid non-convergence. Secondly, a linear approximation fitting model of iso-transmission line is built for high and low energy projection with iso-transmission point pairs solved above. Then the high and low energy projection joint nonlinear solving problem is transformed into solving high and low energy projection iso-transmission line intersection problem, so as to realize the fast decomposition of dual energy projection. Finally, local searching near the intersection of projection matching is used to compensate the error of linear approximation fitting to get more accurate decomposition result. The accuracy and efficiency of the proposed method are demonstrated by numerical simulation.
We have developed a single-breath-hold photoacoustic computed tomography (SBH-PACT) system to reveal detailed angiographic structures in human breasts. SBH-PACT features a deep penetration depth (4 cm in vivo) with high spatial and temporal resolutions (255 µm in-plane resolution and a 10 Hz 2D frame rate). By scanning the entire breast within a single breath hold (~15 s), a volumetric image can be acquired and subsequently reconstructed utilizing 3D back-projection with negligible breathing-induced motion artifacts. SBH-PACT clearly reveals tumors by observing higher blood vessel densities associated with tumors at high spatial resolution, showing early promise for high sensitivity in radiographically dense breasts. In addition to blood vessel imaging, the high imaging speed enables dynamic studies, such as photoacoustic elastography, which identifies tumors by showing less compliance. We imaged breast cancer patients with breast sizes ranging from B cup to DD cup, and skin pigmentations ranging from light to dark. SBH-PACT identified all the tumors without resorting to ionizing radiation or exogenous contrast, posing no health risks.
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