Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy. The placenta window exhibits excellent transparency for light and sound. By combining the placenta window with ultrafast functional photoacoustic microscopy, we were able to investigate the placental development during the entire mouse pregnancy, providing unprecedented spatiotemporal details. Consequently, we examined the acute responses of the placenta to alcohol consumption and cardiac arrest, as well as chronic abnormalities in an inflammation model. We have also observed viral gene delivery at the single-cell level and chemical diffusion through the placenta by using fluorescence imaging. Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes. 
                        more » 
                        « less   
                    
                            
                            NIR-II Nanoprobes: A Review of Components-Based Approaches to Next-Generation Bioimaging Probes
                        
                    
    
            Fluorescence and photoacoustic imaging techniques offer valuable insights into cell- and tissue-level processes. However, these optical imaging modalities are limited by scattering and absorption in tissue, resulting in the low-depth penetration of imaging. Contrast-enhanced imaging in the near-infrared window improves imaging penetration by taking advantage of reduced autofluorescence and scattering effects. Current contrast agents for fluorescence and photoacoustic imaging face several limitations from photostability and targeting specificity, highlighting the need for a novel imaging probe development. This review covers a broad range of near-infrared fluorescent and photoacoustic contrast agents, including organic dyes, polymers, and metallic nanostructures, focusing on their optical properties and applications in cellular and animal imaging. Similarly, we explore encapsulation and functionalization technologies toward building targeted, nanoscale imaging probes. Bioimaging applications such as angiography, tumor imaging, and the tracking of specific cell types are discussed. This review sheds light on recent advancements in fluorescent and photoacoustic nanoprobes in the near-infrared window. It serves as a valuable resource for researchers working in fields of biomedical imaging and nanotechnology, facilitating the development of innovative nanoprobes for improved diagnostic approaches in preclinical healthcare. 
        more » 
        « less   
        
    
                            - Award ID(s):
- 2128821
- PAR ID:
- 10451708
- Date Published:
- Journal Name:
- Bioengineering
- Volume:
- 10
- Issue:
- 8
- ISSN:
- 2306-5354
- Page Range / eLocation ID:
- 954
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
- 
            
- 
            Emerging three-dimensional (3D) printing technology enables the fabrication of optically realistic and morphologically complex tissue-simulating phantoms for the development and evaluation of novel optical imaging products. In this study, we assess the potential to print image-defined neurovascular phantoms with patent channels for contrast-enhanced near-infrared fluorescence (NIRF) imaging. An anatomical map defined from clinical magnetic resonance imaging (MRI) was segmented and processed into files suitable for printing a forebrain vessel network in rectangular and curved-surface biomimetic phantoms. Methods for effectively cleaning samples with complex vasculature were determined. A final set of phantoms were imaged with a custom NIRF system at 785 nm excitation using two NIRF contrast agents. In addition to demonstrating the strong potential of 3D printing for creating highly realistic, patient-specific biophotonic phantoms, our work provides insight into optimal methods for accomplishing this goal and elucidates current limitations of this approach.more » « less
- 
            Tumor-targeted fluorescent probes in the near-infrared spectrum can provide invaluable information about the location and extent of primary and metastatic tumors during intraoperative procedures to ensure no residual tumors are left in the patient's body. Even though the first fluorescence-guided surgery was performed more than 50 years ago, it is still not accepted as a standard of care in part due to the lack of efficient and non-toxic targeted probes approved by regulatory agencies around the world. Herein, we report protease-activated cationic gelatin nanoparticles encapsulating indocyanine green (ICG) for the detection of primary breast tumors in murine models with high tumor-to-background ratios. Upon intravenous administration, these nanoprobes remain optically silent due to the energy resonance transfer among the bound ICG molecules. As the nanoprobes extravasate and are exposed to the acidic tumor microenvironment, their positive surface charges increase, facilitating cellular uptake. The internalized nanoprobes are activated upon proteolytic degradation of gelatin to allow high contrast between the tumor and normal tissue. Since both gelatin and ICG are FDA-approved for intravenous administration, this activatable nanoprobe can lead to quick clinical adoption and improve the treatment of patients undergoing image-guided cancer surgery.more » « less
- 
            Abstract The first line of treatment for most solid tumors is surgical resection of the primary tumor with adequate negative margins. Incomplete tumor resections with positive margins account for over 75% of local recurrences and the development of distant metastases. In cases of oral cavity squamous cell carcinoma (OSCC), the rate of successful tumor removal with adequate margins is just 50–75%. Advanced real‐time imaging methods that improve the detection of tumor margins can help improve success rates,overall safety, and reduce the cost. Fluorescence imaging in the second near‐infrared (NIR‐II) window has the potential to revolutionize the field due to its high spatial resolution, low background signal, and deep tissue penetration properties, but NIR‐II dyes with adequate in vivo performance and safety profiles are scarce. A novel NIR‐II fluorophore, XW‐03‐66, with a fluorescence quantum yield (QY) of 6.0% in aqueous media is reported. XW‐03‐66 self‐assembles into nanoparticles (≈80 nm) and has a systemic circulation half‐life ( t 1/2 ) of 11.3 h. In mouse models of human papillomavirus (HPV)+ and HPV‐ OSCC, XW‐03‐66 outperformed indocyanine green (ICG), a clinically available NIR dye, and enabled intraoperative NIR‐II image‐guided resection of the tumor and adjacent draining lymph node with negative margins. In vitro and in vivo toxicity assessments revealed minimal safety concerns for in vivo applications.more » « less
- 
            The scattering and absorption of light within biological tissue severely limits the penetration depth of optical imaging techniques. Recently, it has been found that water-soluble, strongly absorbing dye molecules, such as tartrazine, can achievein vivotissue transparency by increasing the refractive index of aqueous components in tissue, as predicted by the Lorentz oscillator model and Kramers–Kronig relations. In this study, we topically applied absorbing dye molecules to the abdominal skin of pigmented and nonpigmented mice to enhance the penetration depth of optical coherence tomography (OCT) and photoacoustic microscopy (PAM). In both types of mice, the penetration depth of OCT was significantly improved using tartrazine and 4-aminoantipyrine. As predicted by the Kramers–Kronig relations and absorption spectra of the dyes, mice treated with 4-aminoantipyrine showed significantly improved penetration depth compared to mice treated with tartrazine for the PAM system with 532 nm excitation. These findings further demonstrate the use of absorbing dye molecules for achieving tissue transparency to enhance the penetration depth of depth-resolved optical imaging modalities in skin, thus accelerating the translation of these technologies in clinical areas, such as dermatology.more » « less
 An official website of the United States government
An official website of the United States government 
				
			 
					 
					
 
                                    