Optical imaging in the second near infrared region (NIR-II, 1000-1700 nm) provides higher resolution and deeper penetration depth for accurate and real-time vascular anatomy, blood dynamics, and function information, effectively contributing to the early diagnosis and curative effect assessment of vascular anomalies. Currently, NIR-II optical imaging demonstrates encouraging results including long-term monitoring of vascular injury and regeneration, real-time feedback of blood perfusion, tracking of lymphatic metastases, and imaging-guided surgery. This review summarizes the latest progresses of NIR-II optical imaging for angiography including fluorescence imaging, photoacoustic (PA) imaging, and optical coherence tomography (OCT). The development of current NIR-II fluorescence, PA, and OCT probes (i.e., single-walled carbon nanotubes, quantum dots, rare earth doped nanoparticles, noble metal-based nanostructures, organic dye-based probes, and semiconductor polymer nanoparticles), highlighting probe optimization regarding high brightness, longwave emission, and biocompatibility through chemical modification or nanotechnology, is first introduced. The application of NIR-II probes in angiography based on the classification of peripheral vascular, cerebrovascular, tumor vessel, and cardiovascular, is then reviewed. Major challenges and opportunities in the NIR-II optical imaging for vascular imaging are finally discussed.
Despite bismuth-based energy conversion nanomaterials having attracted extensive attention for nanomedicine, the nanomaterials suffer from major shortcomings including low tumor accumulation, long internal retention time, and undesirable photothermal conversion efficiency (PCE). To combat these challenges, bovine serum albumin and folic acid co-modified Bi2Se3 nanomedicine with rich selenium vacancies (abbreviated as VSe-BS) was fabricated for the second near-infrared (NIR-II) light-triggered photonic hyperthermia. More importantly, selenium vacancies on the crystal planes (0 1 5) and (0 1 11) of VSe-BS with similar formation energies could be distinctively observed via aberration-corrected scanning transmission electron microscopy images. The defect engineering endows VSe-BS with enhanced conductivity, making VSe-BS possess outstanding PCE (54.1%) in the NIR-II biowindow and desirable photoacoustic imaging performance. Tumor ablation studies indicate that VSe-BS possesses satisfactory therapeutic outcomes triggered by NIR-II light. These findings give rise to inspiration for further broadening the biological applications of defect engineering bismuth-based nanomaterials.
Optoacoustic (photoacoustic) imaging has demonstrated versatile applications in biomedical research, visualizing the disease pathophysiology and monitoring the treatment effect in an animal model, as well as toward applications in the clinical setting. Given the complex disease mechanism, multimodal imaging provides important etiological insights with different molecular, structural, and functional readouts in vivo. Various multimodal optoacoustic molecular imaging approaches have been applied in preclinical brain imaging studies, including optoacoustic/fluorescence imaging, optoacoustic imaging/magnetic resonance imaging (MRI), optoacoustic imaging/MRI/Raman, optoacoustic imaging/positron emission tomography, and optoacoustic/computed tomography. There is a rapid development in molecular imaging contrast agents employing a multimodal imaging strategy for pathological targets involved in brain diseases. Many chemical dyes for optoacoustic imaging have fluorescence properties and have been applied in hybrid optoacoustic/fluorescence imaging. Nanoparticles are widely used as hybrid contrast agents for their capability to incorporate different imaging components, tunable spectrum, and photostability. In this review, we summarize contrast agents including chemical dyes and nanoparticles applied in multimodal optoacoustic brain imaging integrated with other modalities in small animals, and provide outlook for further research.
Recently, 2D nanomaterials have received considerable attention in nanomedicine due to their intrinsic optical properties, biocompatibility, and therapeutic effect. Here, 2D germanium telluride (GeTe) nanosheets coated with polyvinylpyrrolidone (PVP) (GeTe-PVP NSs) developed as theranostic agents are reported that can be used for multispectral optoacoustic tomography (MSOT) and fluorescence imaging and therapy of inflammatory bowel disease (IBD). GeTe-PVP NSs, fabricated by simple sonication in ethanol and PVP, show broad optical absorption in visible and near-infrared (NIR) ranges (400–1200 nm) and have intrinsic fluorescence properties. Thus, they provide deeper ex vivo and in vivo MSOT tissue images than gold nanorods or indocyanine green with strong optical absorption in the first NIR window (700–900 nm). In addition, when orally administered to IBD mice, GeTe-PVP NSs exhibit therapeutic efficacy similar to or higher than sulfasalazine, with strong accumulation at inflammatory colon sites. This demonstrates that oral administration of GeTe-PVP NSs may be used to treat inflammatory diseases in the gastrointestinal tract
Rapid volumetric in vivo visualization of circulating microparticles can facilitate new biomedical applications, such as blood flow characterization or targeted drug delivery. However, existing imaging modalities generally lack the sensitivity to detect the weak signals generated by individual micrometer-sized particles distributed across millimeter- to centimeter-scale depths in living mammalian tissues. Also, the temporal resolution is typically insufficient to track the particles in an entire three-dimensional region. Herein, we introduce a new type of monodisperse (4 μm) silica-core microparticle coated with a shell formed by a multilayered structure of carbon nanotubes (CNT) and gold nanoparticles (AuNP) to provide strong optoacoustic (OA) absorption-based contrast. We capitalize on the unique advantages of a state-of-the-art high-frame-rate OA tomography system to visualize and track the motion of these core-shell particles individually and volumetrically as they flow throughout the mouse brain vasculature. The feasibility of localizing individual solid particles smaller than red blood cells opens new opportunities for mapping the blood flow velocity, enhancing the resolution and visibility of OA images, and developing new biosensing assays.
Our study aims to determine whether the beta-adrenergic system is involved in the regulation of lymphatic drainage from the eye. For this purpose, we assessed the effect of 2 topical beta-adrenergic blockers, timolol and betaxolol, commonly used as glaucoma drugs, on lymphatic clearance of albumin from the aqueous humor to neck lymph nodes. Adult mice were treated with either topical timolol, a non-selective β-blocker, 0.5% (n = 8), or topical betaxolol, a selective β1-adrenergic blocker, 0.5% (n = 6) twice daily for 14 days and compared to respective control groups (n = 5 and n = 7). Changes in lymphatic clearance from the eye were assessed using a quantitative in vivo photoacoustic imaging approach. In all subjects, right eye and neck lymph nodes were longitudinally assessed by sequential photoacoustic imaging just prior to near-infrared dye injection into the anterior chamber of the eye, and 20 min, 2 and 4 h after injection. Repeat measurements of mean pixel intensities (MPIs) of right eyes and nodes were performed at all timepoints. The areas under the curves (AUC) were calculated and the AUC of the treated-group was compared to that of controls using the Mann-Whitney U test. The slopes of MPI of each region of interest over time were compared using the linear mixed model after adjusting for IOP decrease after treatment and other parameters such as sex and body weight. In the timolol-treated group, right neck nodes showed significant decrease in AUC signal intensity compared with controls (P = 0.003), and significant decrease in slope of MPI compared with controls (P = 0.0025). In the betaxolol-treated group, right neck nodes showed significant decrease in AUC signal intensity compared with controls (P = 0.02), and significant decrease in slope of MPI compared with controls (P = 0.0069). Topical treatment with timolol and betaxolol reduced lymphatic clearance of albumin from the aqueous humor to the neck lymph nodes. This finding may be relevant for the management of secondary glaucomas and inflammatory eye disease in which the clearance of accumulated proteins and antigen from the eye is important to disease recovery and sight protection. This study suggests that the beta-adrenergic system plays a role in the regulation of lymphatic clearance from the eye.
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