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In Vivo 3D Imaging of Retinal Neovascularization Using Multimodal Photoacoustic Microscopy and Optical Coherence Tomography Imaging
摘要： The pathological process of neovascularization of the retina plays a critical role in causing vision loss in several diseases, including diabetes, retinal vein occlusion, and sickle cell disease. Retinal neovascularization can lead to vitreous hemorrhage and retinal detachment, yet the pathological process of neovascularization is a complex phenomenon under active investigation. Understanding and monitoring retinal neovascularization is critically important in clinical ophthalmology. This study describes a novel multimodal ocular imaging system which combines photoacoustic microscopy (PAM) and a spectral domain optical coherence tomography (SD-OCT) to improve the visualization of retinal neovascularization (RNV), their depth, and the surrounding anatomy in living rabbits. RNV was induced in New Zealand rabbits by intravitreal injection of vascular endothelial growth factor (VEGF). The retinal vasculature before and after injection at various times was monitored and evaluated using multimodal imaging including color fundus photography, fluorescein angiography (FA), OCT, and PAM. In vivo experiments demonstrate that PAM imaging distinctly characterized the location as well as the morphology of individual RNV with high contrast at a safe laser energy of 80 nJ. SD-OCT was used to identify a cross-sectional structure of RNV. In addition, dynamic changes in the retinal morphology and retinal neovascularization were observed at day 4, 5, 6, 7, 9, 11, 14, 28, and day 35 after VEGF injection. PAM demonstrated high-resolution optical absorption of hemoglobin and vascular imaging of the retina and choroid with increased depth of penetration. With the current multimodal imaging system, RNV can be easily visualized in both 2D and 3D angiography. This multimodal ocular imaging system provides improved characterization of the microvasculature in a safe manner in larger rabbit eyes.
关键词： PAM,VEGF,multimodal imaging,optical coherence tomography,photoacoustic microscopy,retinal neovascularization,vascular endothelial growth factor,OCT
更新于2025-09-23 15:22:29
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Dual-Modal In Vivo Fluorescence/Photoacoustic Microscopy Imaging of Inflammation Induced by GFP-Expressing Bacteria
摘要： In this study, dual-modal fluorescence and photoacoustic microscopy was performed for noninvasive and functional in vivo imaging of inflammation induced by green fluorescent protein (GFP) transfected bacteria in mice ear. Our imaging results demonstrated that the multimodal imaging technique is able to monitor the tissue immunovascular responses to infections with molecular specificity. Our study also indicated that the combination of photoacoustic and fluorescence microscopy imaging can simultaneously track the biochemical changes including the bacterial distribution and morphological change of blood vessels in the biological tissues with high resolution and enhanced sensitivity. Consequently, the developed method paves a new avenue for improving the understanding of the pathology mechanism of inflammation.
关键词： GFP-expressing bacteria,fluorescence imaging,biosensor,photoacoustic microscopy,inflammation/infection
更新于2025-09-23 15:22:29
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Photoacoustic microscopy reveals the hemodynamic basis of sphingosine 1-phosphate-induced neuroprotection against ischemic stroke
摘要： Rationale: Emerging evidence has suggested that sphingosine 1-phosphate (S1P), a bioactive metabolite of sphingolipids, may play an important role in the pathophysiological processes of cerebral hypoxia and ischemia. However, the influence of S1P on cerebral hemodynamics and metabolism remains unclear. Material and Methods: Uniquely capable of high-resolution, label-free, and comprehensive imaging of hemodynamics and oxygen metabolism in the mouse brain without the influence of general anesthesia, our newly developed head-restrained multi-parametric photoacoustic microscopy (PAM) is well suited for this mechanistic study. Here, combining the cutting-edge PAM and a selective inhibitor of sphingosine kinase 2 (SphK2) that can increase the blood S1P level, we investigated the role of S1P in cerebral oxygen supply-demand and its neuroprotective effects on global brain hypoxia induced by nitrogen gas inhalation and focal brain ischemia induced by transient middle cerebral artery occlusion (tMCAO). Results: Inhibition of SphK2, which increased the blood S1P, resulted in the elevation of both arterial and venous sO2 in the hypoxic mouse brain, while the cerebral blood flow remained unchanged. As a result, it gradually and significantly reduced the metabolic rate of oxygen. Furthermore, pre-treatment of the mice subject to tMCAO with the SphK2 inhibitor led to decreased infarct volume, improved motor function, and reduced neurological deficit, compared to the control treatment with a less potent R-enantiomer. In contrast, post-treatment with the inhibitor showed no improvement in the stroke outcomes. The failure for the post-treatment to induce neuroprotection was likely due to the relatively slow hemodynamic responses to the SphK2 inhibitor-evoked S1P intervention, which did not take effect before the brain injury was induced. Conclusions: Our results reveal that elevated blood S1P significantly changes cerebral hemodynamics and oxygen metabolism under hypoxia but not normoxia. The improved blood oxygenation and reduced oxygen demand in the hypoxic brain may underlie the neuroprotective effect of S1P against ischemic stroke.
关键词： Sphingosine 1-phosphate,Photoacoustic microscopy,Neuroprotection,Hypoxia,Ischemic stroke
更新于2025-09-23 15:22:29
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Flexibly adjustable depth-of-focus photoacoustic microscopy with spatial light modulation
摘要： Through focusing the excitation laser, optical-resolution photoacoustic microscopy (OR-PAM) is capable of measuring optical absorption properties down to micrometer-scale lateral resolution within biological tissues. The focused Gaussian beam routinely employed in the OR-PAM setups is inadequate for acquiring the volumetric images of biological specimens with thickness from tens micrometers to millimeter without scanning in depth because of the inconsistent lateral resolution along the depth direction due to its short depth of focus (DoF). Here, we integrate a spatial light modulator (SLM) into the optical path of an OR-PAM for realizing the flexibly adjustable DoF. By simply switching the phase patterns assigned onto the SLM interface, three representative illumination beams are produced, including conventional short-DoF Gaussian beam (GB), needle-like Bessel beam (BB), and extended depth-of-focus beam (EDFB). These modulations can be well realized based on the extended Nijboer-Zernike theory. The photoacoustic excitations show variable DoFs ranging from hundreds of micrometers (GB and BB) up to 1.38 mm (EDFB) but a consistent lateral resolution of (cid:2)3.5 lm. The proposed method is confirmed by volumetric imaging of multiple tungsten fibers positioned at different depths.
关键词： spatial light modulation,photoacoustic microscopy,depth-of-focus,extended depth-of-focus beam,Bessel beam,optical-resolution
更新于2025-09-23 15:21:21
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Lifetime-weighted photoacoustic imaging
摘要： Photoacoustic (PA) imaging has been utilized to quantify the lifetime profile of exogenous agents using a series of pump-probe pulses with a varying time delay; however, current techniques typically lead to long acquisition times which are sensitive to motion and cause absorption or photobleaching. We introduce a technique called lifetime-weighted imaging, which uses only three laser pulses to preferentially weight signals from chromophores with long lifetimes (including exogenous contrast agents with triplet excited states such as methylene blue and porphyrins) while nulling chromophores with short picosecond- to nanosecond-scale lifetimes (including hemoglobin). This technique detects the PA signal from a probe pulse either with or without a pump pulse. By subtracting the probe-only signal from the pump-present probe signal, we effectively eliminate signals from chromophores with short lifetimes while preserving PA signals from chromophores with long-lifetimes. We demonstrate the oxygen-dependent lifetime of both methylene blue and porphyrin-lipids and demonstrate both ground-state recovery and excited-state lifetime-weighted imaging. Lifetime-weighted PA imaging may have applications in many molecular imaging application including: photodynamic therapy dosimetry guidance and oxygen sensing.
关键词： methylene blue,lifetime-weighted,photoacoustic microscopy,porhpyrins,lifetime
更新于2025-09-23 15:19:57
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Quantitative analysis on <i>in vivo</i> tumor-microvascular images from optical-resolution photoacoustic microscopy
摘要： Optical-resolution photoacoustic microscopy (OR-PAM) has been shown to be an excellent imaging modality for monitoring and study of tumor microvasculature. However, previous studies focused mainly on the normal tissues and did not quantify the tumor microvasculature. In this study, we present an in vivo OR-PAM imaging of the melanomas and hepatoma implanted in the mouse ear. We quantify the vessel growth by extracting the skeletons of both dense and thin branches of the tumor microvasculature obtained by Hessian matrix enhancement followed by improved two-step multistencils fast marching method. Compared to the previous methods of using OR-PAM for normal tissues, our method was more effective in extracting the binary vascular network in the tumor images and in obtaining the complete and continuous microvascular skeleton maps. Our demonstration of using OR-PAM in improving microvasculature of tumors and quantification of tumor growth would push deep this technology for the early diagnosis and treatment of cancers.
关键词： photoacoustic imaging,tumor neovascular network,quantitative analysis,optical-resolution photoacoustic microscopy
更新于2025-09-19 17:15:36
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Evaluation of Retinal Pigment Epithelium and Choroidal Neovascularization in Rats Using Laser-Scanning Optical-Resolution Photoacoustic Microscopy
摘要： Purpose: To demonstrate the value of the laser-scanning optical-resolution (LSOR)-photoacoustic (PA) microscopy (PAM) system and the conventional multimodal imaging techniques in the evaluation of laser-induced retinal injury and choroidal neovascularization (CNV) in rats. Methods: Different degrees of retinal injury were induced using laser photocoagulation. We compared the LSOR-PAM system with conventional imaging techniques in evaluating retinal injury with or without CNV. Six additional rats, treated with an anti-VEGF antibody or immunoglobulin G immediately after photocoagulation, were imaged 7 and 14 days after injection, and CNV lesion areas were compared. Results: In the retinal injury model, fundus autofluorescence showed well-defined hyperreflection, while the lesion displayed abundant PA signals demonstrating nonuniform melanin distribution in retinal pigment epithelium (RPE). RPE was detected with higher contrast in the PAM B-scan image than optical coherence tomography (OCT). Additionally, the CNV lesion was present with multiple PA signal intensi- ties which distinctly characterized the location and area of CNV as found in fundus fluorescein angiography. Further- more, the decreased PA signals extending from the CNV le- sion were similar to those of the vascular bud in ex vivo im- aging, which was invisible in other in vivo images. When treated with anti-VEGF agents, statistically significant differ- ences can be demonstrated by PAM similar to other mo- dalities. Conclusions: LSOR-PAM can detect the melanin distribution of RPE in laser-induced retinal injury and CNV in rats. PAM imaging provides a potential new tool to evalu- ate the vitality and functionality of RPE in vivo as well as to monitor the development and treatment of CNV.
关键词： Age-related macular degeneration,Retinal pigment epithelium,Multimodal imaging,Photoacoustic microscopy,Choroidal neovascularization
更新于2025-09-12 10:27:22
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Photoacoustic microscopy for evaluating a lipopolysaccharide-induced inflammation model in mice
摘要： Photoacoustic microscopy (PAM) is a noninvasive imaging technique and is excellent to study structural and functional changes in the microcirculation. In this work, a lipopolysaccharide (LPS)-induced inflammation model in mice is noninvasively evaluated by PAM. PAM is used to image the microvascular structural changes in mice for 8 hours after the LPS with different concentrations is applied. Quantitative analysis of five vessel parameters is conducted, which shows that the rate of reduction in microvasculature is highly dependent on the applied LPS concentrations. For low-concentration LPS, changes in the microvasculature are not obvious over the observation period, while for high-concentration LPS, quick and marked reduction in the microvasculature is observed. In addition, changes in capillaries are more significant than those in relatively large vessels. The results show that PAM is able to evaluate the inflammation mouse model by studying structural (and potentially functional) changes in the microcirculation. Further, PAM may have potential for early intervention and treatment plan optimization of sepsis by monitoring the microcirculation and inflammatory response.
关键词： inflammatory response,photoacoustic imaging,photoacoustic microscopy,sepsis,microcirculation
更新于2025-09-10 09:29:36
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1064 nm acoustic resolution photoacoustic microscopy
摘要： Photoacoustic imaging is a non-invasive imaging technique having the advantages of high optical contrast and good acoustic resolution at improved imaging depths. Light transport in biological tissues is mainly characterized by strong optical scattering and absorption. Photoacoustic microscopy is capable of achieving high resolution images at greater depth compared to conventional optical microscopy methods. In this work, we have developed a high-resolution, acoustic resolution photoacoustic microscopy (AR-PAM) system in the near infra-red (NIR) window II (NIR-II, e.g., 1064 nm) for deep tissue imaging. Higher imaging depth is achieved as the tissue scattering at 1064 nm is lesser compared to visible or near infrared window-I (NIR-I). Our developed system can provide a lateral resolution of 130 μm, axial resolution of 57 μm, and image up to 11 mm deep in biological tissues. This 1064-AR-PAM system was used for imaging sentinel lymph node and the lymph vessel in rat. Urinary bladder of rat filled with black ink was also imaged to validate the feasibility of the developed system to study deeply seated organs.
关键词： photoacoustic imaging,deep tissue imaging,urinary bladder,sentinel lymph node,Acoustic resolution photoacoustic microscopy
更新于2025-09-10 09:29:36
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Highly sensitive detection of photo-thermal transient stress by a sub-nanosecond pump probe with surface plasmon resonance
摘要： Photoacoustic microscopy (PAM) has attracted increasing attention for non-invasive functional imaging in biomedicine and biomedical studies. The surface plasmon resonance (SPR) sensor is a potential acoustical detector with high sensitivity and wide bandwidth for use in high-resolution 3D PAM. In this study, we investigated a simple Kretschmann SPR sensor, demonstrating highly sensitive stress detection in the sub-nanosecond timescale by directly inducing photo-thermal transient stress. To do this, we designed and used a sub-nanosecond pump probe system. The SPR sensor clearly detected the transient response from the thermal elastic effect, while a simple pump-probe sensor without SPR did not detect it. Our experimental results demonstrate a simple SPR sensor that can detect stress with high sensitivity and sub-nanosecond time resolution. This technique could be used in high-resolution 3D PAM by mounting a small biomedical sample on the sensor.
关键词： photoacoustic microscopy,sub-nanosecond pump probe,surface plasmon resonance,photo-thermal transient stress,high-resolution 3D imaging
更新于2025-09-10 09:29:36