Organic nanoparticle-doped microdroplets as dual-modality contrast agents for ultrasound microvascular flow and photoacoustic imaging.

Tumor blood vessels are chaotic and abundantly distributed, owing to their heterogeneity. Therefore, imaging techniques which reveal abnormalities of tumor vasculature play significant roles in both mechanistic and clinical diagnostic tumor studies. Photoacoustic (PA) imaging uses the intrinsic characteristics of hemoglobin, to acquire tumor hemodynamic information, while ultrasound (US) imaging provides information about tumoral vessel structures and blood flow. To improve the imaging contrast performance, hydrogel-based microdroplets were designed for both US blood flow and PA imaging in this study. The microdroplets served as carriers for PA contrast agent solution in the innermost part while oil and hydrogel formed the inner and outer layers of the droplets. In vitro experiments firstly demonstrated the dual modality contrast effects of the microdroplets on US flow determination and PA imaging. In vivo experiments were then carried out in both healthy nude mice and nude mice with subcutaneous tumor to validate the contrast effects and to monitor the duration of contrast effects in animals. Using the dual-modality microdroplets, we were able to obtain distinct edges of tumor and blood flow mapping of the tumor microvascular with improved sensitivity up to 11.09 dB for PA and 6.69 dB for US flow. Besides, the in vivo evaluation with microdroplets showed US flow enhancement for more than 60 min. Therefore, the microdroplets are able to provide the contrast effects for both US flow and PA in a relative long duration and have potential to be applied in the tumor related diagnoses and studies.

A Handheld Real-Time Photoacoustic Imaging System for Animal Neurological Disease Models: From Simulation to Realization.

This article provides a guide to design and build a handheld, real-time photoacoustic (PA) imaging system from simulation to realization for animal neurological disease models. A pulsed laser and array-based ultrasound (US) platform were utilized to develop the system for evaluating vascular functions in rats with focal ischemia or subcutaneous tumors. To optimize the laser light delivery, finite element (FE)-based simulation models were developed to provide information regarding light propagation and PA wave generation in soft tissues. Besides, simulations were also conducted to evaluate the ideal imaging resolution of the US system. As a result, a PA C-scan image of a designed phantom in 1% Lipofundin was reconstructed with depth information. Performance of the handheld PA system was tested in an animal ischemia model, which revealed that cerebral blood volume (CBV) changes at the cortical surface could be monitored immediately after ischemia induction. Another experiment on subcutaneous tumors showed the anomalous distribution of the total hemoglobin concentration (HbT) and oxygen saturation (SO2), while 3D and maximum intensity projection (MIP) PA images of the subcutaneous tumors are also presented in this article. Overall, this system shows promise for monitoring disease progression in vascular functional impairments.

Evolutional Characterization of Photochemically Induced Stroke in Rats: a Multimodality Imaging and Molecular Biological Study.

Photochemically induced cerebral ischemia is an easy-manipulated, reproducible, relatively noninvasive, and lesion controllable model for translational study of ischemic stroke. In order to longitudinally investigate the characterization of the model, magnetic resonance imaging, 18F-2-deoxy-glucose positron emission tomography, fluorescence, and bioluminescence imaging system were performed in correlation with triphenyl tetrazolium chloride (TTC), hematoxylin-eosin staining, and immunohistochemistry examinations of glial fibrillary acidic protein, CD68, NeuN, von willebrand factor, and α-smooth muscle actin in the infarct zone. The results suggested that the number of inflammatory cells, astrocytes, and neovascularization significantly elevated in peri-infarct region from day 7 and a belt of macrophage/microglial and astrocytes was formed surrounding infarct lesion at day 14. Both vasogenic and cytotoxic edema, as well as blood brain-barrier leakage, occurred since day 1 after stroke induction and gradually attenuated with time. Numerous cells other than neuronal cells infiltrated into infarct lesion, which resulted in no visible TTC negative regional existence at day 14. Furthermore, recovery of cerebral blood flow and glucose utilization in peri-infarct zone were noted and more remarkably than that in infarct core following the stroke progression. In conclusion, these characterizations may be highly beneficial to the development of therapeutic strategies for ischemic stroke.