The blood-brain barrier (BBB) is commonly known to be distributed evenly within the central nervous system. This study elucidates previously unexplored physiological phenomena associated with the spatial heterogeneity of the BBB. We found that isoflurane facilitates hemispheric lateralization in BBB permeability, leading to different responses between the left and right hemispheres. To substantiate this finding, we used neural optical imaging to comprehensively map the spatial homeostasis of BBB. Image segmentation and feature extraction exhibited hemispheric lateralization in vascular microstructure and function. Gait analysis confirmed that the lateralization of BBB homeostasis influences behavioral functions. Our results indicate that the left hemisphere enhances its self-protective mechanisms by disrupting the balance of mitochondrial fission and fusion, resulting in structural changes in mitochondria and reduced ATP (adenosine 5′-triphosphate) production, which are crucial for maintaining BBB homeostasis. This study offers insights into the molecular pathways that regulate BBB integrity and their potential implications for drug delivery.

Intravenous injection is a rapid, low-cost, and direct method that is commonly used to deliver multifarious biotherapeutics and vaccines. However, intravenous injection often causes trauma or tissue injury that requires professional operation. Transdermal drug delivery overcomes the aforementioned defects, and the microneedles (MNs) array is one of the most promising transdermal drug delivery platforms. Timely, precise, and non-invasive monitoring and evaluation of the effects of MNs in transdermal administration is significant to the research of drug efficiency response to specific diseases. In this sense, photoacoustic computed tomography (PACT), which provides wavelength-selective and deep-penetrating optical contrast, could be a promising imaging tool for in situ evaluation of the treatment effects. In this work, we propose the use of PACT to non-invasively assess the effects of real-time drug delivery in glioma tumors through transdermal administration with degradable indocyanine green-loaded hyaluronic acid MNs (ICG-HA-MNs). The outcome is systematically and quantitatively compared with that via intravenous injection. It is found that the photoacoustic signals of ICG in the tumor site express a faster elevation and shorter duration time in the intravenous injection group; by contrast, the photoacoustic signals demonstrate a lower intensity but prolonged duration time in the MNs group. The observed phenomenon indicates faster response but shorter drug duration for intravenous injection, which is in contrast with the lower loading but prolonged performance for transdermal drug delivery with MNs. These results exhibit good consistency with the earlier, common-sense findings reported from other aspects, confirming that PACT can serve as a potential imaging tool to precisely, non-invasively, and quickly evaluate in situ drug delivery effects and provide constructive guidance for the design and fabrication of microneedles.

Early detection of hepatic fibrosis remains a critical unmet need due to the limited sensitivity of conventional elastography in capturing microstructural and biomechanical changes. In this study, we developed photoacoustic elastomicroscopy (PAEM), a multi-parametric imaging platform that synergizes high-resolution photoacoustic microscopy with time-of-flight (ToF)-based elastography to quantitatively map tissue stiffness and visualize fibrotic microarchitecture. Validated using PDMS phantoms and a drug-induced murine fibrosis model, PAEM can detect early-stage fibrosis through microstructural biomarkers—pseudo-lobule formation and crevice-area expansion, with a relatively high area under the curve (AUC) > 0.91. However, architectural ambiguity in advanced fibrotic stages gradually reduces PAEM’s diagnostic accuracy, necessitating complementary reliance on ToF-based measurements for auxiliary staging. In our results, ToF-based elasticity biomarkers revealed progressive stiffness increases with a significant velocity increase of 3.7% in 1-week fibrosis. Furthermore, experimental PAEM outperformed shear wave elastography (SWE) in early-stage sensitivity by identifying significant stiffness changes, quantitatively 7-fold greater velocity differential sensitivity than SWE (5.39% vs. 0.77% change), between healthy and 3-week fibrotic liver tissue. All-stage fibrosis exhibited a considerable stiffness rise (AUC > 0.95), correlating strongly with histopathological severity and serum examination. By integrating structural and mechanical biomarkers, PAEM offers a translational tool for early diagnosis, longitudinal monitoring, and staging of hepatic fibrosis, which can potentially be extended for wider applications in tumor margin delineation and other fibrotic pathologies in soft tissue.