Ischemic stroke (IS) is one of the leading causes of death and accounts for 85% of stroke cases. Since the symptoms are not obvious, diagnosis of IS, particularly at an early stage, is a great challenge. Photoacoustic imaging combines high sensitivity of optical imaging and fine resolution of ultrasonography to non-invasively provide structural and functional information of IS.Methods: We adopted three rapid photoacoustic imaging systems with varying characteristics, including a portable handheld photoacoustic system, high-sensitivity bowl-shaped array photoacoustic computed tomography (PACT), and high-resolution photoacoustic microscopy (PAM) to assess the stereoscopic and comprehensive pathophysiological status of IS at an early stage. Two representative models of IS, referring to photothrombosis and middle cerebral artery occlusion (MCAO) models, were established to verify the feasibility of photoacoustic imaging detection.Results: Non-invasive, rapid PACT of the IS model in mouse provided structural information of the brain lesion, achieving early disease identification (5 min after the onset of disease). Moreover, it was able to dynamically reflect disease progression. Quantitative high-resolution PAM allowed observation of pathological changes in the microvascular system of mouse brain. In terms of functional imaging, significant differences in oxygen saturation (sO2) levels between infarcted and normal areas could be observed by PACT, permitting effective functional parameters for the diagnosis of IS.Conclusions: We used PACT to perform full-view structural imaging and functional imaging of sO2 in IS at the macroscopic level, and then observed the microvascular changes in the infarcted area at the microscopic level by using PAM. This work may provide new tools for the early diagnosis of IS and its subsequent complications as well as assessment of disease progression.
The detection of cancer micrometastasis for early diagnosis and treatment poses a great challenge for conventional imaging techniques. The aim of our study was to evaluate the performance of photoacoustic imaging (PAI) in detecting hepatic micrometastases from melanoma at a very early stage and in aiding tumor resection by intraoperative guidance. Methods: In vivo studies were performed by following protocols approved by the Ethical Committee for Animal Research at Xiamen University. First, a mouse model of B16 melanoma metastatic to the liver (n 5 10) was established to study the development of micrometastases in vivo. Next, the mice were imaged by a scalable PAI instrument, ultrasound, 9.4-T highresolution MRI, PET/CT, and bioluminescence imaging. PAI scans acquired with optical wavelengths of 680-850 nm were kept spectrally unmixed by using a linear least-squares method to differentiate various components. Differences in signal-to-background ratios among different modalities were determined with the 2-tailed paired t test. The diagnostic results were assessed with histologic examination. Excised liver samples from patients diagnosed with hepatic cancer were also examined to identify the tumor boundaries. Surgical removal of metastatic melanoma was precisely guided in vivo by the portable PAI system. Results: PAI was able to detect metastases as small as approximately 400 μm at a depth of up to 7 mm in vivo-a size that is smaller than can be detected with ultrasound and MRI. The tumor-to-liver ratio for PAI at 8 d (4.2 ± 0.2, n 5 6) and 14 d (9.2 ± 0.4, n 5 5) was significantly higher than for PET/CT (1.8 ± 0.1, n 5 5, and 4.5 ± 0.2, n 5 5, respectively; P , 0.001 for both). Functional PAI revealed dynamic oxygen saturation changes during tumor growth. The limit of detection was approximately 219 cells/μL in vitro. We successfully performed intraoperative PAI-guided surgery in vivo using the portable PAI system. Conclusion: Our findings offer a rapid and effective complementary clinical imaging application to noninvasively detect micrometastases and guide intraoperative resection.
Core–shell metal nanostructures with versatile functions have attracted extensive attention and are highly desirable for imaging and therapeutic purposes.
Nanobubbles (NBs) have recently gained interest in cancer imaging and therapy due to the fact that nanoparticles with the size range of 1−1000 nm can extravasate into permeable tumor types through the enhanced permeability and retention (EPR) effect. However, the therapeutic study of NBs was only limited to drug delivery or cavitation. Herein, we developed ultrasound-evoked massive NB explosion to strikingly damage the surrounding cancer. The dual-function agent allows synergistic mechanical impact and photodynamic therapy of the tumors and enhances imaging contrast. Moreover, the mechanical explosion improved the light delivery efficiency in biological tissue to promote the effect of photodynamic therapy. Under ultrasound/ photoacoustic imaging guidance, we induced on-the-spot bubble explosion and photodynamic therapy of tumors at a depth of centimeters in vivo. The mechanical impact of the explosion can enhance delivery of the photosensitizers. Ultrasound explicitly revealed the cancer morphology and exhibited fast NB perfusion. Generated mechanical damage and release of mixture agents demonstrated remarkable synergetic anticancer effects on deep tumors. This finding also offers a new approach and insight into treating cancers.
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