3D MR neurography with gadolinium contrast to improve the visualization of pelvic nerves and the branches.

Objective: To evaluate the effectiveness of 3D NerveVIEW sequence with gadolinium contrast on the visualization of pelvic nerves and their branches compared to that without contrast. Methods: Participants were scanned twice using 3D NerveVIEW sequence with and without gadolinium contrast to acquire pelvic nerve images. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and contrast ratio of the nerves were calculated and compared to determine the quality of images. To subjectively assess, using a 3-point scale, branch nerves critical to therapeutic decision-making, including the pelvic splanchnic nerve and pelvic plexus, the superior gluteal nerve, and the pudendal nerve. Results: In the 32 eligible participants after using contrast, the CNRs of the images of nerve-to-bone and nerve-to-vessel significantly increased (p < 0.05). The CR of the images with contrast of all nerve-to-surrounding tissues (i.e., bone, muscle, blood vessels, and fat) were also found significantly higher (p < 0.05). The assessment of observers also shows higher scores for images with contrast compared to images without contrast. Conclusion: The 3D NerveVIEW sequence combined with gadolinium contrast improved vascular suppression, increased the contrast between pelvic nerves and surrounding tissue, and enhanced the visualization of nerves and their branches. This study may be helpful for the technically challenging preoperative planning of pelvic diseases surgery.

Endovaginal coil for pelvic high-resolution magnetic resonance imaging of cervical cancer: a preliminary parameter optimization study.

Background: The diagnosis of early-stage cervical cancer through conventional magnetic resonance imaging (MRI) remains challenging, highlighting a greater need for pelvic high-resolution MRI (HR MRI). This study used our research team's endovaginal coil imaging to optimize scanning parameters and aimed to achieve HR MRI of the pelvis and determine its clinical value. Methods: Fifty participants were recruited prospectively for this cross-sectional study conducted at the First Affiliated Hospital of Chongqing Medical University from January 2023 to November 2023. Initially, 10 volunteers requiring pelvic imaging diagnosis underwent pelvic MRI with the endovaginal coil combined with a conventional external array coil to test and optimize the scanning parameters. Subsequently, 40 patients who were highly suspected or diagnosed with cervical cancer were randomly assigned to undergo an initial pelvic scan with an external array coil with subsequent examinations of both the conventional coil and the endovaginal coil. Two experienced radiologists performed quantitative analyses, measuring signals and calculating the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and contrast (C). They also conducted qualitative analyses, evaluating imaging artifacts, anatomical structures, and overall image quality. The paired sample t-test and Wilcoxon rank-sum test were conducted to compare the statistical differences between the two sets of images, while the intraclass correlation coefficient (ICC) and Kappa consistency tests were used to assess the measurement and scoring consistency between the two radiologists. Results: The optimized endovaginal images had higher mean SNR, CNR, and C values (18.62±7.85, 16.04±7.72, and 0.73±0.11, respectively) compared to the conventional images (6.77±2.36, 4.47±2.05, and 0.47±0.12, respectively). Additionally, the ratings for imaging artifacts, anatomical structures, and overall quality of the endovaginal images were all 4 [interquartile range (IQR) 4, 4]; meanwhile, the conventional images scored lower with ratings of 4 (IQR 3, 4), 3 (IQR 3, 3), and 3 (IQR 3, 3) for SNR, CNR, and C, respectively. All analysis results underwent paired-sample t-tests or Wilcoxon rank-sum tests between the two groups, yielding a P value <0.001. The optimized endovaginal images also showed improved resolution with a reconstructed voxel size of 0.11 mm3, and HR MRI was successfully achieved. The ICC values for the measurements were 0.914, 0.947, and 0.912, respectively, and for the ratings, the measurement was 0.923, indicating excellent consistency between the two physicians (ICC/Kappa value between 0.85 and 1.00). Conclusions: Endovaginal technology, which provides precise clinical information for the diagnosis of cervical cancer, provides straightforward operation and exceptional imaging quality, making it highly suitable for expanded clinical use.

Non-contrast enhanced MRI for efficiency evaluation of high-intensity focused ultrasound in adenomyosis ablation.

OBJECTIVE: To investigate the value of T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) in evaluating the therapeutic effect of high-intensity focused ultrasound (HIFU) in adenomyosis ablation. MATERIAL AND METHODS: One hundred eighty-nine patients with adenomyosis were treated with HIFU. The ablation areas on T2WI and DWI sequences were classified into different types: type I, relatively ill-defined rim or unrecognizable; subtype IIa, well-defined rim with hyperintensity; subtype IIb, well-defined rim with hypointensity. The volume of ablation areas on T2WI (VT2WI) and DWI (VDWI) was measured and compared with the non-perfused volume (NPV), and linear regression was conducted to analyze their correlation with NPV. RESULTS: The VT2WI of type I and type II (subtype IIa and subtype IIb) were statistically different from the corresponding NPV (p = 0.004 and 0.024, respectively), while no significant difference was found between the VDWI of type I and type II with NPV (p = 0.478 and 0.561, respectively). In the linear regression analysis, both VT2WI and VDWI were positively correlated with NPV, with R2 reaching 0.96 and 0.97, respectively. CONCLUSIONS: Both T2WI and DWI have the potential for efficient evaluation of HIFU treatment in adenomyosis, and DWI can be a replacement for CE-T1WI to some extent.

pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy.

Tumour-associated macrophages (TAMs), as one of the most abundant tumour-infiltrating immune cells, play a pivotal role in tumour antigen clearance and immune suppression. M2-like TAMs present a heightened lysosomal acidity and protease activity, limiting an effective antigen cross-presentation. How to selectively reprogram M2-like TAMs to reinvigorate anti-tumour immune responses is challenging. Here, we report a pH-gated nanoadjuvant (PGN) that selectively targets the lysosomes of M2-like TAMs in tumours rather than the corresponding organelles from macrophages in healthy tissues. Enabled by the PGN nanotechnology, M2-like TAMs are specifically switched to a M1-like phenotype with attenuated lysosomal acidity and cathepsin activity for improved antigen cross-presentation, thus eliciting adaptive immune response and sustained tumour regression in tumour-bearing female mice. Our findings provide insights into how to specifically regulate lysosomal function of TAMs for efficient cancer immunotherapy.

Dissecting extracellular and intracellular distribution of nanoparticles and their contribution to therapeutic response by monochromatic ratiometric imaging.

Efficient delivery of payload to intracellular targets has been identified as the central principle for nanomedicine development, while the extracellular targets are equally important for cancer treatment. Notably, the contribution of extracellularly distributed nanoparticles to therapeutic outcome is far from being understood. Herein, we develop a pH/light dual-responsive monochromatic ratiometric imaging nanoparticle (MRIN), which functions through sequentially lighting up the intracellular and extracellular fluorescence signals by acidic endocytic pH and near-infrared light. Enabled by MRIN nanotechnology, we accurately quantify the extracellular and intracellular distribution of nanoparticles in several tumor models, which account for 65-80% and 20-35% of total tumor exposure, respectively. Given that the majority of nanoparticles are trapped in extracellular regions, we successfully dissect the contribution of extracellularly distributed nanophotosensitizer to therapeutic efficacy, thereby maximize the treatment outcome. Our study provides key strategies to precisely quantify nanocarrier microdistribtion and engineer multifunctional nanomedicines for efficient theranostics.

A pH-/Enzyme-Responsive Nanoparticle Selectively Targets Endosomal Toll-like Receptors to Potentiate Robust Cancer Vaccination.

Toll-like receptor (TLR) agonists are potent immune-stimulators that hold great potential in vaccine adjuvants as well as cancer immunotherapy. However, TLR agonists in free form are prone to be eliminated quickly by the circulatory system and cause systemic inflammation side effects. It remains a challenge to achieve precise release of TLR7/8 agonist in the native form at the receptor site in the endosomal compartments while keeping stable encapsulation and inactive in nontarget environment. Here, we report a pH-/enzyme-responsive TLR7/8 agonist-conjugated nanovaccine (TNV), which responds intelligently to the acidic environment and cathepsin B in the endosome, precisely releases TLR7/8 agonist to activate its receptor signaling at the endosomal membrane, stimulates DCs maturation, and provokes specific cellular immunity. In vivo experiments demonstrate outstanding prophylactic and therapeutic efficacy of TNV in mouse melanoma and colon cancer. The endosome-targeted responsive nanoparticle strategy provides a potential delivery toolbox of adjuvants to advance the development of tumor nanovaccines.

pH-Amplified CRET Nanoparticles for In Vivo Imaging of Tumor Metastatic Lymph Nodes.

Noninvasive imaging strategies have been extensively investigated for in vivo mapping of sentinel lymph nodes (SLNs). However, the current imaging strategies fail to accurately assess tumor metastatic status in SLNs with high sensitivity. Here we report pH-amplified self-illuminating near-infrared nanoparticles, which integrate chemiluminescence resonance energy transfer (CRET) and signal amplification strategy, enabling accurate identification of metastatic SLNs. After draining into lymph nodes, the nanoparticles were phagocytosed and dissociated in acidic phagosomes of inflammatory macrophages to emit near-infrared luminescent light. Using these nanoparticles, we successfully differentiated tumor metastatic lymph nodes from benign ones. These nanoparticles also exhibited excellent imaging capability for early detection of metastatic SLNs in diverse animal tumor models with small tumor volume (100-200 mm3 ).

Quantitative imaging of intracellular nanoparticle exposure enables prediction of nanotherapeutic efficacy.

Nanoparticle internalisation is crucial for the precise delivery of drug/genes to its intracellular targets. Conventional quantification strategies can provide the overall profiling of nanoparticle biodistribution, but fail to unambiguously differentiate the intracellularly bioavailable particles from those in tumour intravascular and extracellular microenvironment. Herein, we develop a binary ratiometric nanoreporter (BiRN) that can specifically convert subtle pH variations involved in the endocytic events into digitised signal output, enabling the accurately quantifying of cellular internalisation without introducing extracellular contributions. Using BiRN technology, we find only 10.7-28.2% of accumulated nanoparticles are internalised into intracellular compartments with high heterogeneity within and between different tumour types. We demonstrate the therapeutic responses of nanomedicines are successfully predicted based on intracellular nanoparticle exposure rather than the overall accumulation in tumour mass. This nonlinear optical nanotechnology offers a valuable imaging tool to evaluate the tumour targeting of new nanomedicines and stratify patients for personalised cancer therapy.