Deep Learning Enhanced Volumetric Photoacoustic Imaging of Vasculature in Human.

The development of high-performance imaging processing algorithms is a core area of photoacoustic tomography. While various deep learning based image processing techniques have been developed in the area, their applications in 3D imaging are still limited due to challenges in computational cost and memory allocation. To address those limitations, this work implements a 3D fully-dense (3DFD) U-net to linear array based photoacoustic tomography and utilizes volumetric simulation and mixed precision training to increase efficiency and training size. Through numerical simulation, phantom imaging, and in vivo experiments, this work demonstrates that the trained network restores the true object size, reduces the noise level and artifacts, improves the contrast at deep regions, and reveals vessels subject to limited view distortion. With these enhancements, 3DFD U-net successfully produces clear 3D vascular images of the palm, arms, breasts, and feet of human subjects. These enhanced vascular images offer improved capabilities for biometric identification, foot ulcer evaluation, and breast cancer imaging. These results indicate that the new algorithm will have a significant impact on preclinical and clinical photoacoustic tomography.

Review of imaging test phantoms.

Significance: Photoacoustic tomography has emerged as a prominent medical imaging technique that leverages its hybrid nature to provide deep penetration, high resolution, and exceptional optical contrast with notable applications in early cancer detection, functional brain imaging, drug delivery monitoring, and guiding interventional procedures. Test phantoms are pivotal in accelerating technology development and commercialization, specifically in photoacoustic (PA) imaging, and can be optimized to achieve significant advancements in PA imaging capabilities. Aim: The analysis of material properties, structural characteristics, and manufacturing methodologies of test phantoms from existing imaging technologies provides valuable insights into their applicability to PA imaging. This investigation enables a deeper understanding of how phantoms can be effectively employed in the context of PA imaging. Approach: Three primary categories of test phantoms (simple, intermediate, and advanced) have been developed to differentiate complexity and manufacturing requirements. In addition, four sub-categories (tube/channel, block, test target, and naturally occurring phantoms) have been identified to encompass the structural variations within these categories, resulting in a comprehensive classification system for test phantoms. Results: Based on a thorough examination of literature and studies on phantoms in various imaging modalities, proposals have been put forth for the development of multiple PA-capable phantoms, encompassing considerations related to the material composition, structural design, and specific applications within each sub-category. Conclusions: The advancement of novel and sophisticated test phantoms within each sub-category is poised to foster substantial progress in both the commercialization and development of PA imaging. Moreover, the continued refinement of test phantoms will enable the exploration of new applications and use cases for PA imaging.

One-Step, On-Site Chemical Printing of a 3D Plasmon-Coupled Silver Nanocoral Substrate toward SERS-Based POCT.

Surface-enhanced Raman scattering (SERS) with the advantages of high sensitivity, nondestructive analysis, and a unique fingerprint effect shows great potential in point-of-care testing (POCT). However, SERS faces challenges in rapidly constructing a substrate with high repeatability, homogeneity, and sensitivity, which are the key factors that restrict its practical applications. In this study, we propose a one-step chemical printing strategy for synthesizing a three-dimensional (3D) plasmon-coupled silver nanocoral (AgNC) substrate (only need about 5 min) without any pretreatments and complex instruments. The galvanic replacement between AgNO3 and Cu sheets will provide both Ag0 for the formation of silver nanostructures and Cu2+ for the polymerization of fish sperm DNA (FSDNA). The protection of AgNCs is facilitated by the crosslinked FSDNA, which can improve the stability of the substrate and promote the control of its coral-like morphology. The obtained substrate displays excellent capacity of signal enhancement due to the 3D plasmon coupling both between nanocoral tentacles and between nanocorals and Cu sheets as well. Therefore, the AgNC substrates display high activity (enhancement factor = 1.96 × 108) and uniformity (RSD < 6%). Food colorants have been widely used in various foods to improve their color, but the inevitable toxicity of colorants seriously threatens food safety. Therefore, the proposed AgNC substrates were used to directly quantify three kinds of weak-affinity food colorant molecules including Brilliant Blue, Allura Red, and Sunset Yellow assisted by the capture by cysteamine hydrochloride (CA), showing the detection limits (S/N = 3) of 0.053, 0.087, and 0.089 ppm, respectively. The SERS method has been further applied in the detection of the three kinds of food colorants in both complex food samples and urine with recoveries of 91-119%. The satisfactory detection results suggest that the facile preparation strategy of AgNC substrates will be widely used in SERS-based POCT to promote the development of food safety and on-site healthcare.

LINC01116 boosts the progression of pituitary adenoma via regulating miR-744-5p/HOXB8 pathway.

Pituitary adenoma (PA) is one of the common intracranial tumors. In order to optimize status quo, seeking out potential biomarkers for pituitary adenoma diagnosis and treatment is urgent and important. Long non-coding RNAs (lncRNAs) have been related with progression of various cancers. Based on this reason and unknown role of long intergenic non-protein coding RNA 1116 (LINC01116) in pituitary adenoma, we aimed to explore the function and molecular mechanism of LINC01116 in pituitary adenoma. The RT-qPCR analysis showed that LINC01116 was abnormally overexpressed in pituitary adenoma cells. Down-regulated LINC01116 effectively suppressed cell proliferation and migration as well as epithelial-mesenchymal transition (EMT) progression in pituitary adenoma. Additionally, LINC01116 could competitively sponge miR-744-5p as shown by RIP, RNA pull down and luciferase reporter assays. Similarly, we also proved that homeobox B8 (HOXB8) was the target gene of miR-744-5p in pituitary adenoma cells. In the end, the rescue assays unmasked that HOXB8 could effectually reverse inhibition effect of LINC016 knockdown on pituitary adenoma cells proliferation, migration and EMT, further suggesting that LINC01116 expedited the pituitary adenoma progression by up-regulating HOXB8. Taken together, LINC01116 boosted the progression of pituitary adenoma cells via regulating miR-744-5p/HOXB8 pathway.

Perfluoropolyether Nanoemulsion Encapsulating Chlorin e6 for Sonodynamic and Photodynamic Therapy of Hypoxic Tumor.

Sonodynamic therapy (SDT) has emerged as an important modality for cancer treatment. SDT utilizes ultrasound excitation, which overcomes the limitations of light penetration in deep tumors, as encountered by photodynamic therapy (PDT) which uses optical excitations. A comparative study of these modalities using the same sensitizer drug can provide an assessment of their effects. However, the efficiency of SDT and PDT is low in a hypoxic tumor environment, which limits their applications. In this study, we report a hierarchical nanoformulation which contains a Food and Drug Administration (FDA) approved sensitizer chlorin, e6, and a uniquely stable high loading capacity oxygen carrier, perfluoropolyether. This oxygen carrier possesses no measurable cytotoxicity. It delivers oxygen to overcome hypoxia, and at the same time, boosts the efficiency of both SDT and PDT. Moreover, we comparatively analyzed the efficiency of SDT and PDT for tumor treatment throughout the depth of the tissue. Our study demonstrates that the strengths of PDT and SDT could be combined into a single multifunctional nanoplatform, which works well in the hypoxia environment and overcomes the limitations of each modality. The combination of deep tissue penetration by ultrasound and high spatial activation by light for selective treatment of single cells will significantly enhance the scope for therapeutic applications.

3D Bioprinting a human iPSC-derived MSC-loaded scaffold for repair of the uterine endometrium.

Common events in the clinic, such as uterine curettage or inflammation, may lead to irreversible endometrial damage, often resulting in infertility in women of childbearing age. Currently, tissue engineering has the potential to achieve tissue manipulation, regeneration, and growth, but personalization and precision remain challenges. The application of "3D cell printing" is more in line with the clinical requirements of tissue repair. In this study, a porous grid-type human induced pluripotent stem cell-derived mesenchymal stem cell (hiMSC)-loaded hydrogel scaffold was constructed using a 3D bioprinting device. The 3D-printed hydrogel scaffold provided a permissive in vitro living environment for hiMSCs and significantly increased the survival duration of transplanted hiMSCs when compared with hiMSCs administered locally in vivo. Using an endometrial injury model, we found that hiMSC transplantation can cause early host immune responses (the serological immune response continued for more than 1 month, and the local immune response continued for approximately 1 week). Compared with the sham group, although the regenerative endometrium failed to show full restoration of the normal structure and function of the lining, implantation of the 3D-printed hiMSC-loaded scaffold not only promoted the recovery of the endometrial histomorphology (endometrial tissue and gland regeneration) and the regeneration of endometrial cells (stromal cells and epithelial cells) and endothelial cells but also improved endometrial receptivity functional indicators, namely, pinopode formation and leukemia inhibitory factor and αvß3 expression, which partly restored the embryo implantation and pregnancy maintenance functions of the injured endometrium. These indicators were significantly better in the 3D-printed hiMSC-loaded scaffold group than in the unrepaired (empty) group, the hiMSCs alone group and the 3D scaffold group, and the empty group showed the worst repair results. Our study confirm that the 3D-printed hiMSC-loaded hydrogel scaffold may be a promising material for endometrial repair.

Investigation of the effects of laminin present in the basal lamina of the peripheral nervous system on axon regeneration and remyelination using the nerve acellular scaffold.

This study aimed to investigate the effects of laminin (LN) located in the basal lamina, which are important components of the peripheral nervous system-extracellular matrix, on axon regeneration and remyelination. Nerve acellular scaffolds (NASs) (S-untreated) were prepared using the acellular technique. The active component LN in the NASs was blocked (S-LN- ) or upregulated (S-LN+ ); S-LN+ contained seven times more LN than did the S-untreated group. The adhesion capacity of Schwann cells (SCs) to the three types of NAS (S-untreated, S-LN- , and S-LN+ ) was assessed in vitro. Our results showed that the adhesion of SCs to the NASs was significantly reduced in the S-LN- group, whereas no difference was observed between the S-LN+ and S-untreated groups. The pretreated NASs were used to repair nerves in a nerve injury mouse model with the animals divided into four groups (S-LN- group, S-untreated group, S-LN+ group, and autograft group). Two weeks after surgery, although there was no difference in the S-LN- group, S-untreated group and S-LN+ group, the newly formed basal lamina in the S-LN- group were significantly lower than those in the other two groups. Four weeks after surgery, the S-LN+ group had higher numbers of newly generated axons and their calibers, more myelinated fibers, thicker myelin sheaths, increased myelin basic protein expression, and improved recovery of neural function compared to those of the S-LN- and S-untreated groups, but all of these parameters were significantly worse than those of the autograft group. Downregulation of the LN level in the NAS leads to a reduction in all of the above parameters.

Dual Scan Mammoscope (DSM)-A New Portable Photoacoustic Breast Imaging System With Scanning in Craniocaudal Plane.

OBJECTIVE: We present a new photoacoustic tomography system that provides visualization of angiographic features in a human breast with mammogram-like images. METHODS: The system images a mildly compressed breast, from both top and bottom, using two 128-element, 2.25 MHz linear transducer arrays and line optical fiber bundles. The mild compression is achieved using plastic films, which is a more comfortable experience for the patient compared to rigid metal plates used in a traditional mammogram. RESULTS: We could image a D cup-sized breast of 7 cm thickness within 1 minute and achieve a spatial resolution of around 1 mm in all directions. CONCLUSION: Our system possesses the benefits of portability, speedy scanning, and patient comfort. The craniocaudal-view images can be easily correlated with existing imaging modalities for data interpretation. SIGNIFICANCE: Early cancer detection plays a critical role in overall cancer survival rate. Our system may address the limitations of mammogram and offer a radiation-free screening technique for patients with dense breasts.