Dynamic characterization of vascular response and treatment in oral traumatic ulcer in mice via photoacoustic imaging.

Background: Dynamic surveillance of vasculature is essential for evaluating the healing of oral ulcer. Existing techniques used in vascular imaging face limitations, such as inadequate spatial resolution, restricted diagnostic depth, and the necessity of exogenous contrast agents. Therefore, this study aimed to use robust photoacoustic imaging (PAI) for the dynamic monitoring of vascular response during healing and the associated treatment process of oral ulcer. Methods: Kunming mice (male, 8 weeks old, 31-41 g) were treated with 50% acetic acid for 90 s on the tongue mucosa for induction of oral traumatic ulcer. Mice were randomly divided into three groups (n=12): the control, compound chamomile and lidocaine hydrochloride gel (CCLH), and phycocyanin (PC) groups. PAI was then conducted on days 0, 2, 3, 5, and 7 to obtain vessel parameters of the ulcer area, including vessel intensity, density, mean diameter, maximum diameter, and curvature. Immunohistochemical and hematoxylin and eosin (HE) staining were performed on days 3 and 7 to assess microvessel density and inflammation score. The ulcer healing rate and body weight changes were evaluated for clinical observation. Results: Beginning on the second day after ulcer induction, there was a progressive increase over time in blood intensity and vessel parameters, including vascular density and diameter. On day 7, the CCLH and PC groups demonstrated significantly higher measures than did the control group in terms of blood intensity (P<0.05 and P<0.01), vascular density (both P values <0.05), mean diameter (both P values <0.01), and maximum diameter (P<0.01 and P<0.05). Vessel curvature in the two treatment groups exhibited no significant differences compared to that in the control group (both P values >0.05). The effects of vascular morphological changes were further supported by the histological and clinical outcomes. On day 7, compared to that of the control group, the level of microvessel density was significantly higher in both the CCLH (P<0.01) and PC (P<0.05) groups. The histopathological score in PC group was significantly lower than that of the control group on day 7 (P<0.05). Additionally, compared to that of the control group, the healing rates of the CCLH (P<0.01) and PC groups (P<0.05) were superior on day 7. On day 3, the control group showed more weight loss than did the CCLH (P<0.05) and PC (P<0.01) groups. Conclusions: These findings indicate that PAI is a valuable strategy for the dynamic and quantitative analysis of vascular alterations in oral traumatic ulcers and support its prospective application in improving clinical treatment.

Imaging Modalities for Evaluating Lymphedema.

Lymphedema is a progressive condition. Its therapy aims to reduce edema, prevent its progression, and provide psychosocial aid. Nonsurgical treatment in advanced stages is mostly insufficient. Therefore-in many cases-surgical procedures, such as to restore lymph flow or excise lymphedema tissues, are the only ways to improve patients' quality of life. Imaging modalities: Lymphoscintigraphy (LS), near-infrared fluorescent (NIRF) imaging-also termed indocyanine green (ICG) lymphography (ICG-L)-ultrasonography (US), magnetic resonance lymphangiography (MRL), computed tomography (CT), photoacoustic imaging (PAI), and optical coherence tomography (OCT) are standardized techniques, which can be utilized in lymphedema diagnosis, staging, treatment, and follow-up. Conclusions: The combined use of these imaging modalities and self-assessment questionnaires deliver objective parameters for choosing the most suitable surgical therapy and achieving the best possible postoperative outcome.

The effect of tumor vascular remodeling and immune microenvironment activation induced by radiotherapy: quantitative evaluation with magnetic resonance/photoacoustic dual-modality imaging.

Background: Tumor radiotherapy combined with immunotherapy for solid tumors has been proposed, but tumor vascular structure abnormalities and immune microenvironment often affect the therapeutic effect of tumor, and multimodal imaging technology can provide more accurate and comprehensive information in tumor research. The purpose of this study was to evaluate the dynamic monitoring of tumor blood vessels and microenvironment induced by radiotherapy by magnetic resonance/photoacoustic (MR/PA) imaging, and to explore its application value in radiotherapy combined with immunotherapy. Methods: The tumor-bearing mice were randomly allocated into six groups, which received different doses of radiation therapy (2 Gy ×14 or 8 Gy ×3) and anti-programmed death ligand-1 (PD-L1) antibody for two consecutive weeks. MR/PA imaging was used to noninvasively evaluate the response of tumor to different doses of radiotherapy, combined with histopathological techniques to observe the tumor vessels and microenvironment. Results: The inhibitory effect of high-dose radiotherapy on tumors was significantly greater than that of low-dose radiotherapy, with the MR images revealing that the signal intensity decreased significantly (P<0.05). Compared with those in the other groups, the tumor vascular density decreased significantly (P<0.01), and the vascular maturity index increased significantly in the low-dose group (P<0.05). The PA images showed that the deoxyhemoglobin and total hemoglobin levels decreased and the SO2 level increased after radiation treatment (P<0.05). In addition, the high-dose group had an increased number of tumor-infiltrating lymphocytes (CD4+ T and CD8+ T cells) (P<0.01, P<0.05) and natural killer cells (P<0.001) and increased PD-L1 expression in the tumors (P<0.05). The combination of radiotherapy and immunotherapy increased the survival rate of the mice (P<0.05), and a regimen of an 8 Gy dose of radiation combined with immunotherapy inhibited tumor growth and increased the survival rate of the mice to a greater degree than the 2 Gy radiation dose with immunotherapy combination (P=0.002). Conclusions: Differential fractionation radiotherapy doses exert biological effects on tumor vascular and the immune microenvironment, and MR/PA can be used to evaluate tumor vascular remodeling after radiotherapy, which has certain value for the clinical applications of radiotherapy combined with immunotherapy.

Laser-activated nanoparticles for ultrasound/photoacoustic imaging-guided prostate cancer treatment.

Prostate cancer (PCa) is the most common malignant tumor in men. Prostate-specific membrane antigen (PSMA), which is overexpressed on the surface of Prostate cancer cells, may serve as a potential therapeutic target. Recently, image-guided and targeted therapy for prostate cancers has attracted much attention by using Prostate-specific membrane antigen targeting nanoparticle. In this study, we produced PSMA-targeted light-responsive nanosystems. These nanosystems of liquid perfluorocarbon cores and polymer shells were loaded with the photosensitizer IR780 and therapeutic drugs paclitaxel. The liquid perfluorocarbon (PFP) in nanoparticles can perform ultrasound-enhanced imaging by liquid-gas transition and promote the deliver and release of paclitaxel. IR780 can perform photothermal therapy (PTT) guided by photoacoustic (PA) imaging. Combination treatment with photothermal therapy and chemotherapy exhibited excellent inhibition of cell proliferation in vitro and a significant therapeutic effect in vivo. In conclusion, we successfully formulated PSMA-targeted nanosystems with precision targeting and ultrasound/PA dual-modality imaging for anti-tumor effects.

Near-Infrared Spectroscopy for the In Vivo Monitoring of Biodegradable Implants in Rats.

Magnesium (Mg) alloys possess unique properties that make them ideal for use as biodegradable implants in clinical applications. However, reports on the in vivo assessment of these alloys are insufficient. Thus, monitoring the degradation of Mg and its alloys in vivo is challenging due to the dynamic process of implant degradation and tissue regeneration. Most current works focus on structural remodeling, but functional assessment is crucial in providing information about physiological changes in tissues, which can be used as an early indicator of healing. Here, we report continuous wave near-infrared spectroscopy (CW NIRS), a non-invasive technique that is potentially helpful in assessing the implant-tissue dynamic interface in a rodent model. The purpose of this study was to investigate the effects on hemoglobin changes and tissue oxygen saturation (StO2) after the implantation of Mg-alloy (WE43) and titanium (Ti) implants in rats' femurs using a multiwavelength optical probe. Additionally, the effect of changes in the skin on these parameters was evaluated. Lastly, combining NIRS with photoacoustic (PA) imaging provides a more reliable assessment of tissue parameters, which is further correlated with principal component analysis.

Size-tunable ICG-based contrast agent platform for targeted near-infrared photoacoustic imaging.

Near-infrared photoacoustic imaging (NIR-PAI) combines the advantages of optical and ultrasound imaging to provide anatomical and functional information of tissues with high resolution. Although NIR-PAI is promising, its widespread use is hindered by the limited availability of NIR contrast agents. J-aggregates (JA) made of indocyanine green dye (ICG) represents an attractive class of biocompatible contrast agents for PAI. Here, we present a facile synthesis method that combines ICG and ICG-azide dyes for producing contrast agents with tunable size down to 230 nm and direct functionalization with targeting moieties. The ICG-JA platform has a detectable PA signal in vitro that is two times stronger than whole blood and high photostability. The targeting ability of ICG-JA was measured in vitro using HeLa cells. The ICG-JA platform was then injected into mice and in vivo NIR-PAI showed enhanced visualization of liver and spleen for 90 min post-injection with a contrast-to-noise ratio of 2.42.

Computational analysis of drug free silver triangular nanoprism theranostic probe plasmonic behavior for in-situ tumor imaging and photothermal therapy.

INTRODUCTION: The advanced features of plasmonic nanomaterials enable initial high accuracy detection with different therapeutic intervention. Computational simulations could estimate the plasmonic heat generation with a high accuracy and could be reliably compared to experimental results. This proposed combined theoretical-experimental strategy may help researchers to better understand other nanoparticles in terms of plasmonic efficiency and usability for future nano-theranostic research. OBJECTIVES: To develop innovative computationally-driven approach to quantify any plasmonic nanoparticles photothermal efficiency and effects before their use as therapeutic agents. METHODS: This report introduces drug free plasmonic silver triangular nanoprisms coated with polyvinyl alcohol biopolymer (PVA-SNT), for in vivo photoacoustic imaging (PAI) guided photothermal treatment (PTT) of triple-negative breast cancer mouse models. The synthesized PVA-SNT nanoparticles were characterized and a computational electrodynamic analysis was performed to evaluate and predict the optical and plasmonic photothermal properties. The in vitro biocompatibility and in vivo tumor abalation study was performed with MDA-MB-231 human breast cancer cell line and in nude mice model. RESULTS: The drug free 140 µg∙mL-1 PVA-SNT nanoparticles with 1.0 W∙cm-2 laser irradiation for 7 min proved to be an effective and optimized theranostic approach in terms of PAI guided triple negative breast cancer treatment. The PVA-SNT nanoparticles exhibits excellent biosafety, photostability, and strong efficiency as PAI contrast agent to visualize tumors. Histological analysis and fluorescence-assisted cell shorter assay results post-treatment apoptotic cells, more importantly, it shows substantial damage to in vivo tumor tissues, killing almost all affected cells, with no recurrence. CONCLUSION: This is a first complete study on computational simulations to estimate the plasmonic heat generation followed by drug free plasmonic PAI guided PTT for cancer treatment. This computationally-driven theranostic approach demonstrates an innovative thought regarding the nanoparticles shape, size, concentration, and composition which could be useful for the prediction of photothermal heat generation in precise nanomedicine applications.

Optical ultrasound sensors for photoacoustic imaging: a narrative review.

Optical ultrasound sensors have been increasingly employed in biomedical diagnosis and photoacoustic imaging (PAI) due to high sensitivity and resolution. PAI could visualize the distribution of ultrasound excited by laser pulses in biological tissues. The information of tissues is detected by ultrasound sensors in order to reconstruct structural images. However, traditional ultrasound transducers are made of piezoelectric films that lose sensitivity quadratically with the size reduction. In addition, the influence of electromagnetic interference limits further applications of traditional ultrasound transducers. Therefore, optical ultrasound sensors are developed to overcome these shortcomings. In this review, optical ultrasound sensors are classified into resonant and non-resonant ones in view of physical principles. The principles and basic parameters of sensors are introduced in detail. Moreover, the state of the art of optical ultrasound sensors and applications in PAI are also presented. Furthermore, the merits and drawbacks of sensors based on resonance and non-resonance are discussed in perspectives. We believe this review could provide researchers with a better understanding of the current status of optical ultrasound sensors and biomedical applications.

Molecular imaging of cardiovascular inflammation.

Cardiovascular diseases (CVDs), including atherosclerosis, are chronic inflammatory diseases characterised by a complex and evolving tissue micro-environment. Molecular heterogeneity of inflammatory responses translates into clinical outcomes. However, current medical imaging modalities are unable to reveal the cellular and molecular events at a level of detail that would allow more accurate and timely diagnosis and treatment. This is an inherent limitation of the current imaging tools, which are restricted to anatomical or functional data. Molecular imaging-the visualisation and quantification of molecules in the body-is already established in the clinic in the form of PET, yet the use of PET in CVD is limited. In this visual review, we will guide you through the current state of molecular imaging research, assessing the respective strengths and weaknesses of molecular imaging modalities, including those already being used in the clinic such as PET and MRI and emerging technologies at preclinical stage, such as photoacoustic imaging. We discuss the basic principles of each technology and provide key examples of their application in imaging inflammation in CVD and the added value into the diagnostic decision-making process. Finally, we discuss the barriers to the rapid successful clinical translation of these novel diagnostic modalities. LINKED ARTICLES: This article is part of a themed issue on Molecular imaging - visual themed issue. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.21/issuetoc.

In Vivo Imaging of Biodegradable Implants and Related Tissue Biomarkers.

Non-invasive longitudinal imaging of osseointegration of bone implants is essential to ensure a comprehensive, physical and biochemical understanding of the processes related to a successful implant integration and its long-term clinical outcome. This study critically reviews the present imaging techniques that may play a role to assess the initial stability, bone quality and quantity, associated tissue remodelling dependent on implanted material, implantation site (surrounding tissues and placement depth), and biomarkers that may be targeted. An updated list of biodegradable implant materials that have been reported in the literature, from metal, polymer and ceramic categories, is provided with reference to the use of specific imaging modalities (computed tomography, positron emission tomography, ultrasound, photoacoustic and magnetic resonance imaging) suitable for longitudinal and non-invasive imaging in humans. The advantages and disadvantages of the single imaging modality are discussed with a special focus on preclinical imaging for biodegradable implant research. Indeed, the investigation of a new implant commonly requires histological examination, which is invasive and does not allow longitudinal studies, thus requiring a large number of animals for preclinical testing. For this reason, an update of the multimodal and multi-parametric imaging capabilities will be here presented with a specific focus on modern biomaterial research.

Photoacoustic imaging in evaluating early intestinal ischemia injury and reperfusion injury in rat models.

BACKGROUND: It remains a challenge to distinguish whether the damaged intestine is viable in treating acute mesenteric ischemia. In this study, photoacoustic imaging (PAI) was used to observe intestinal tissue viability after ischemia and reperfusion injury in rats. METHODS: An in vivo study was conducted using forty male SD rats, which were randomly divided into a sham-operated (SO) group, a 1 h ischemia group, a 2 h ischemia group, and an ischemia-reperfusion (I/R) group with 10 rats in each group. In the ischemia group, the superior mesenteric artery (SMA) was isolated and clamped for 1 and 2 h, respectively, and in the I/R group, after ischemia for 1 h, the clamp was removed and reperfused for 1 h. The same time interval was used in the SO group. Immediately after establishing the animal model, a PAI examination was performed, and the small intestine was collected for histopathology. RESULTS: The levels of PAI parameters Hb, HbR, MAP 760, and MAP 840 were increased to different degrees in the ischemia groups, especially in the 2 h ischemia group, compared with the SO group (P<0.05), and with prolongation of the ischemia time, the injury was aggravated. All PAI signal levels except HbO in the I/R group were higher than those in the control group, and the increased range differed, especially in Hb and MAP 840. Using western blot, compared with the SO group, the BAX increased significantly in the 2 h ischemia group (P<0.05), and Caspase-3 in the experimental group was significantly higher than in the SO group (P<0.05). The level of HIF-1α increased in the 2 h ischemia group and I/R group (P<0.05), and TUNEL staining showed that the number of positive apoptotic nuclei in the 2 h ischemia group was significantly higher than in the SO group (P<0.05). Hematoxylin-eosin (HE) staining showed that ischemia for 2 hours was the most serious, with obvious mucosal damage, extensive epithelial injury, and bleeding. CONCLUSIONS: PAI can be used as an effective tool to detect acute intestinal ischemia injury and quantitatively evaluate tissue viability.

NIR-II bioimaging of small organic molecule.

In recent years, people have been actively exploring new imaging methods with high biological imaging performance because the clinical image definition and depth in vivo cannot meet the requirements of early diagnosis and prognosis. Based on the traditional near-infrared region I (NIR-I), the molecular probe of the near-infrared region II (NIR-II) is further explored and developed. In the NIR-II region due to the wavelength is longer than the NIR-I region can effectively reduce the molecular scattering, optical absorption of the organization, the organization of spontaneous fluorescence negligible, thus the NIR-II Fluorescence imaging (FI) can get deeper penetration depth, higher signal-to-background ratio (SBR) and better spatiotemporal resolution, FI in NIR-II region are an important and rapidly developing research region for future imaging. In the NIR-II fluorophore, small organic molecule fluorophore has attracted much attention because of its good biocompatibility and good pharmacokinetic properties. In this review, we briefly introduced the existing NIR-II organic small molecule fluorophores, and introduced the existing relatively mature methods for improving quantum yield and water solubility, and the small molecule dyes on FI of various improvement methods, also briefly introduces the small molecules of photoacoustic imaging (PAI), and a brief introduction of imaging-guided surgery (IGS) for some small organic molecules, finally, a reasonable prospect is made for the development of small organic molecules.

Two-Dimensional Photoacoustic/Ultrasonic Endoscopic Imaging Based on a Line-Focused Transducer.

Existing acoustic-resolution photoacoustic/ultrasonic endoscopy (PA/USE) generally employs a point-focused transducer for ultrasound detection, which is only sensitive in its focal region, thus the lateral resolution and sensitivity drop dramatically when the targets move far from its focus. Even if a dynamic focusing algorithm is applied, the sensitivity out of the transducer focus is still much lower than that in the focus in ultrasonic imaging mode. In this work, we propose an acoustic-resolution PA/USE with a line-focused transducer to realize automatic focusing for the first time. In comparison to a point-focused transducer, the line-focused transducer emits a more uniform sound field, causing the original signal intensity and signal-to-noise ratio (SNR) of the front and rear targets to be closer in the radial direction, which is beneficial for improving target signal uniformity in ultrasonic imaging. Simultaneously, we improved the resolution of the defocus area by modifying a prior work of back-projection (BP) reconstruction algorithm typically used in point-focused transducer based PAE and applying it to line-focused PA/USE. This combined approach may significantly enhance the depth of field of ultrasonic imaging and the resolution of the defocus zone in PA/US imaging, compared to the conventional method. Sufficient numerical simulations and phantom experiments were performed to verify this method. The results show that our method can effectively improve the lateral resolution in the image's defocused region to achieve automatic focusing and perfectly solve the defect of the target signal difference in the far-focus region in ultrasonic imaging, while also enhancing the image SNR and contrast. The proposed method in this paper lays foundations for the realization of photoacoustic/ultrasonic combined endoscopy with enhanced lateral resolution and depth of field, which can potentially benefit a many of biomedical applications.

Development of Dual-Frequency PMUT Arrays Based on Thin Ceramic PZT for Endoscopic Photoacoustic Imaging.

This paper presents a dual-frequency piezoelectric micromachined ultrasonic transducer (pMUT) array based on thin ceramic PZT for endoscopic photoacoustic imaging (PAI) applications. With a chip size of 7 × 7 mm2, the pMUT array consists of 256 elements, half of which have a lower resonant frequency of 1.2 MHz and the other half have a higher resonant frequency of 3.4 MHz. Ceramic PZT, with outstanding piezoelectric coefficients, has been successfully thinned down to a thickness of only 4 µ by using wafer bonding and chemical mechanical polishing (CMP) techniques and employed as the piezoelectric layer of the pMUT elements. The diaphragm diameters of the lower-frequency and higher-frequency elements are 220 µm and 120 µm, respectively. The design methodology, multiphysics modeling, fabrication process, and characterization of the pMUTs are presented in detail. The fabricated pMUT array has been fully characterized via electrical, mechanical, and acoustic measurements. The measured maximum responsivities of the lower- and higher- frequency elements reach 110 nm/V and 30 nm/V at their respective resonances. The measured cross-couplings of the lower-frequency elements and higher-frequency elements are about 9% and 5%, respectively. Furthermore, PAI experiments with pencil leads embedded into an agar phantom have been conducted, which clearly shows the advantages of using dual-frequency pMUT arrays to provide comprehensive photoacoustic images with high spatial resolution and large signal-to-noise ratio simultaneously.

Design, Development, and Multi-Characterization of an Integrated Clinical Transrectal Ultrasound and Photoacoustic Device for Human Prostate Imaging.

The standard diagnostic procedure for prostate cancer (PCa) is transrectal ultrasound (TRUS)-guided needle biopsy. However, due to the low sensitivity of TRUS to cancerous tissue in the prostate, small yet clinically significant tumors can be missed. Magnetic resonance imaging (MRI) with TRUS fusion biopsy has recently been introduced as a way to improve the identification of clinically significant PCa in men. However, the spatial errors in coregistering the preprocedural MRI with the real-time TRUS causes false negatives. A real-time and intraprocedural imaging modality that can sensitively detect PCa tumors and, more importantly, differentiate aggressive from nonaggressive tumors could largely improve the guidance of biopsy sampling to improve diagnostic accuracy and patient risk stratification. In this work, we seek to fill this long-standing gap in clinical diagnosis of PCa via the development of a dual-modality imaging device that integrates the emerging photoacoustic imaging (PAI) technique with the established TRUS for improved guidance of PCa needle biopsy. Unlike previously published studies on the integration of TRUS with PAI capabilities, this work introduces a novel approach for integrating a focused light delivery mechanism with a clinical-grade commercial TRUS probe, while assuring much-needed ease of operation in the transrectal space. We further present the clinical potential of our device by (i) performing rigorous characterization studies, (ii) examining the acoustic and optical safety parameters for human prostate imaging, and (iii) demonstrating the structural and functional imaging capabilities using deep-tissue-mimicking phantoms. Our TRUSPA experimental studies demonstrated a field-of-view in the range of 130 to 150 degrees and spatial resolutions in the range of 300 µm to 400 µm at a soft tissue imaging depth of 5 cm.

Molecular imaging of inflammation - Current and emerging technologies for diagnosis and treatment.

Inflammation is a key factor in multiple diseases including primary immune-mediated inflammatory diseases e.g. rheumatoid arthritis but also, less obviously, in many other common conditions, e.g. cardiovascular disease and diabetes. Together, chronic inflammatory diseases contribute to the majority of global morbidity and mortality. However, our understanding of the underlying processes by which the immune response is activated and sustained is limited by a lack of cellular and molecular information obtained in situ. Molecular imaging is the visualization, detection and quantification of molecules in the body. The ability to reveal information on inflammatory biomarkers, pathways and cells can improve disease diagnosis, guide and monitor therapeutic intervention and identify new targets for research. The optimum molecular imaging modality will possess high sensitivity and high resolution and be capable of non-invasive quantitative imaging of multiple disease biomarkers while maintaining an acceptable safety profile. The mainstays of current clinical imaging are computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US) and nuclear imaging such as positron emission tomography (PET). However, none of these have yet progressed to routine clinical use in the molecular imaging of inflammation, therefore new approaches are required to meet this goal. This review sets out the respective merits and limitations of both established and emerging imaging modalities as clinically useful molecular imaging tools in addition to potential theranostic applications.

Exploration of FeIII-Phenol Complexes for Photothermal Therapy and Photoacoustic Imaging.

Photothermal therapy (PTT) has received extensive attention because of its excellent antitumor effect, specific selectivity, and minimal invasiveness. FeIII-phenol complexes with good biocompatibility and biosafety have widespread applications in PTT. However, the comparison of different FeIII-phenol complexes for photoacoustic imaging (PAI) and PTT has been rarely reported. Herein, we prepared a series of FeIII-phenol complexes using phenols with different structures via a simple one-step method. We then systematically investigated their ultraviolet-visible (UV-vis) absorbance, photothermal performance, and PAI capability. Phenols, including ortho diphenol or triphenol, were important components of FeIII-phenol complexes with strong capacity for UV-vis absorbance, photothermal performance, and PAI. The representative FeIII-pyrocatechol (PC) and FeIII-tannic acid (TA) complexes exhibited excellent photothermal performance and could induce MCF-7 cell death with laser irradiation. Moreover, FeIII-PC and FeIII-TA complexes emitted strong photoacoustic (PA) signals and might be used as PA agents. After comprehensive consideration, FeIII-TA complexes were identified as optimal PTT agents with PAI for cancer treatment. This study has a high reference value for the application of FeIII-phenol complexes to cancer diagnosis and therapy.

Brain Vascular Imaging Techniques.

Recent major improvements in a number of imaging techniques now allow for the study of the brain in ways that could not be considered previously. Researchers today have well-developed tools to specifically examine the dynamic nature of the blood vessels in the brain during development and adulthood; as well as to observe the vascular responses in disease situations in vivo. This review offers a concise summary and brief historical reference of different imaging techniques and how these tools can be applied to study the brain vasculature and the blood-brain barrier integrity in both healthy and disease states. Moreover, it offers an overview on available transgenic animal models to study vascular biology and a description of useful online brain atlases.

Semimetal nanomaterials of antimony as highly efficient agent for photoacoustic imaging and photothermal therapy.

In this study we report semimetal nanomaterials of antimony (Sb) as highly efficient agent for photoacoustic imaging (PAI) and photothermal therapy (PTT). The Sb nanorod bundles have been synthesized through a facile route by mixing 1-octadecane (ODE) and oleyl amine (OAm) as the solvent. The aqueous dispersion of PEGylated Sb NPs, due to its broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, is applicable as a photothermal agent driven by 808 nm laser with photothermal conversion efficiency up to 41%, noticeably higher than most of the PTT agents reported before. Our in vitro experiments also showed that cancer cell ablation effect of PEGylated Sb NPs was dependent on laser power. By intratumoral administration of PEGylated Sb NPs, 100% tumor ablation can be realized by using NIR laser irradiation with a lower power of 1 W/cm(2) for 5 min (or 0.5 W/cm(2) for 10 min) and no obvious toxic side effect is identified after photothermal treatment. Moreover, intense PA signal was also observed after intratumoral injection of PEGylated Sb NPs and NIR laser irradiation due to their strong NIR photoabsorption, suggesting PEGylated Sb NPs as a potential NIR PA agent. Based on the findings of this work, further development of using other semimetal nanocrystals as highly efficient NIR agents can be achieved for vivo tumor imaging and PTT.