Cell-based drug delivery systems have shown promising capability for tumor-targeted therapy owing to the intrinsic tumor-homing and drug-carrying property of some living cells. However, imaging ...tracking of their migration and bio-effects is urgently needed for clinical application, especially for glioma. Here, we report the inflammation-activatable engineered neutrophils by internalizing doxorubicin-loaded magnetic mesoporous silica nanoparticles (ND-MMSNs) which can provide the potential for magnetic resonance (MR) imaging tracking of the drug-loaded cells to actively target inflamed brain tumor after surgical resection of primary tumor. The phagocytized D-MMSNs possess high drug loading efficiency and do not affect the host neutrophils' viability, thus remarkably improving intratumoral drug concentration and delaying relapse of surgically treated glioma. Our study offers a new strategy in targeted cancer theranostics through combining the merits of living cells and nanoparticle carriers.
The imbalance between oxidants and antioxidants in cancer cells would evoke oxidative stress-induced cell death, which has been demonstrated to be highly effective in treating malignant tumors. ...Sonodynamic therapy (SDT) adopts ultrasound (US) as the excitation source to induce the production of reactive oxygen species (ROS), which emerges as a noninvasive therapeutic strategy with deep tissue penetration depth and high clinical safety. Herein, we construct novel sonoactivated oxidative stress amplification nanoplatforms by coating MnO2 on Au nanoparticle-anchored black phosphorus nanosheets and decorating soybean phospholipid subsequently (Au/BP@MS). The Au/BP@MS exhibit increased ROS generation efficiency under US irradiation in tumor tissues due to Au/BP nanosensitizer-induced improvement of electron-hole separation as well as MnO2-mediated O2 generation and GSH depletion, thus leading to notable inhibition effect on tumor growth. Moreover, tumor microenvironment-responsive biodegradability of Au/BP@MS endows them with enhanced magnetic resonance imaging guidance and clinical potential for cancer theranostics.
A novel sonoactivated tumor theranostic nanoplatform was successfully constructed by coating MnO2 on Au nanoparticle-anchored black phosphorus nanosheets, which resulted in improved separation of electron-hole pairs for enhanced sonodynamic effect. Display omitted
•The anchored Au NPs on BP nanosheets could prominently improve electron-hole separation for enhanced SDT.•The MnO2 coating on Au/BP could strengthen SDT efficacy through O2 generation and GSH depletion.•The release of Mn2+ in acidic tumor microenvironment would function as T1-weighted MR imaging agents.•Au/BP@MS exhibited superior biocompatibility and biodegradability.
Proton resonance frequency shift (PRFS) MR thermometry is commonly used to measure temperature in thermotherapy. The method requires a baseline temperature map and is therefore motion sensitive. ...Several referenceless MR thermometry methods were proposed to address this problem but their performances have never been compared. This study compared the performance of five referenceless methods through simulation, heating of ex vivo tissues and in vivo imaging of the brain and liver of healthy volunteers. Mean, standard deviation, root mean square, 2/98 percentiles of error were used as performance metrics. Probability density functions (PDF) of the error distribution for these methods in the different tests were also compared. The results showed that the phase gradient method (PG) exhibited largest error in all scenarios. The original method (ORG) and the complex field estimation method (CFE) had similar performance in all experiments. The phase finite difference method (PFD) and the near harmonic method (NH) were better than other methods, especially in the lower signal-to-noise ratio (SNR) and fast changing field cases. Except for PG, the PDFs of each method were very similar among the different experiments. Since phase unwrapping in ORG and NH is computationally demanding and subject to image SNR, PFD and CFE would be good choices as they do not need phase unwrapping. The results here would facilitate the choice of appropriate referenceless methods in various MR thermometry applications.
Ultrasound stimulation has recently emerged as a non-invasive method for modulating brain activity in animal and human studies with healthy subjects. Whether brain diseases such as Alzheimer's ...disease, epilepsy, and depression can be treated using ultrasound stimulation still needs to be explored. Recent studies have reported that ultrasound stimulation suppressed epileptic seizures in a rodent model of epilepsy. These findings raise the crucial question of whether ultrasound stimulation can inhibit seizures in non-human primates with epilepsy. Here, we addressed this critical question. We confirmed that ultrasound stimulation significantly reduced the frequency of seizures in acute epileptic monkeys. Furthermore, the results showed that the number and duration of seizures were reduced, whereas the inter-seizure interval was increased after ultrasound stimulation. Besides, no significant brain tissue damage was observed by T2-weighted MR imaging. Our results are of great importance for future clinical applications of ultrasound neuromodulation in patients with epilepsy.
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•Ultrasound stimulation can inhibit seizures in non-human primates with epilepsy•Ultrasound stimulation reduces the number and duration of seizures•Ultrasound stimulation is a safe, noninvasive therapeutic method for epilepsy
Ultrasound Technology; Medical Imaging; Neuroscience
It has been a long-cherished wish in biomedicine research to have an imaging tool to visualize gene expression, with good spatiotemporal resolution, in rodent and primate animals noninvasively and ...longitudinally. To this purpose, we here present a novel genetic encoded magnetic resonance imaging reporter, i.e., GEM reporter, for noninvasive visualization of cell-specific gene expression. The GEM reporter was developed through codon modification of a bacteria-originated manganese (Mn) binding protein, allowing the sequestration of endogenous Mn in local tissues. When expressed in bacteria, plant and animals, GEM reporter can robustly produce high image contrast in T1-weighted MRI without additional substrates or contrast agents. Importantly, GEM reporter can be tracked inherently by MRI in specific cells and tissues. These findings support GEM reporter as a versatile marker for deciphering gene expression spatiotemporally in living subjects.
Reducing the radiation tracer dose and scanning time during positron emission tomography (PET) imaging can reduce the cost of the tracer, reduce motion artifacts, and increase the efficiency of the ...scanner. However, the reconstructed images to be noisy. It is very important to reconstruct high-quality images with low-count (LC) data. Therefore, we propose a deep learning method called LCPR-Net, which is used for directly reconstructing full-count (FC) PET images from corresponding LC sinogram data.
Based on the framework of a generative adversarial network (GAN), we enforce a cyclic consistency constraint on the least-squares loss to establish a nonlinear end-to-end mapping process from LC sinograms to FC images. In this process, we merge a convolutional neural network (CNN) and a residual network for feature extraction and image reconstruction. In addition, the domain transform (DT) operation sends a priori information to the cycle-consistent GAN (CycleGAN) network, avoiding the need for a large amount of computational resources to learn this transformation.
The main advantages of this method are as follows. First, the network can use LC sinogram data as input to directly reconstruct an FC PET image. The reconstruction speed is faster than that provided by model-based iterative reconstruction. Second, reconstruction based on the CycleGAN framework improves the quality of the reconstructed image.
Compared with other state-of-the-art methods, the quantitative and qualitative evaluation results show that the proposed method is accurate and effective for FC PET image reconstruction.
Benefiting from treating diseases at the genetic level, gene therapy has been considered a new revolution in the biomedical field. However, the extracellular and intracellular barriers during gene ...transport such as enzymatic degradation and endo-/lysosomal sequestration significantly compromise the therapeutic efficacy. Though photochemical internalization (PCI) has emerged as a promising approach for causing endo-/lysosomal leakage with translocation of the internalized molecules into the cytosol, its effect is still unsatisfactory due to the insufficient light penetration depth. Here, we develop tumor microenvironment-specific enhanced gene delivery by means of ROS generated from the in situ cascaded catalytic reactions in tumors involving GOx-mediated redox reaction and Mn
-mediated Fenton-like reaction. The efficient enzymatic protection and successful endo-/lysosomal escape of cargo gene complexes have been demonstrated. Moreover, anti-Twist siRNA-loaded G@MMSNs-P exhibit tumor-specific biodegradation, excellent T
-weighted MR imaging, and significant inhibitory effects against breast cancer growth and pulmonary metastasis.
Hepatic transporters facilitate the uptake of xenobiotic compounds and confer immense potential as multimodality reporters, as they can uptake multitude of bioluminescent, fluorescence, near ...Infra‐red (NIR), and magnetic resonance imaging (MRI) compounds. Here, it is aimed to identify the prospects of three human hepatocyte membrane proteins, organic anion transporters (OATP) 1B1, OATP1B3, and sodium‐taurocholate cotransporting polypeptide in tracing the transplanted cells dynamics, by the uptake of clinically approved MRI compound, gadolinium ethoxybenzyl‐diethylenetriaminepentaacetic acid (GD‐EOB DTPA) or NIR fluorescent dye, Indocyanine Green (ICG). First, OATP1B1 is introduced as new MRI reporter which is the human orthologue of previously established rodent (Oatp1a1) reporter. Comparative sequential assays by assimilating MR image parameters reveal OATP1B3 as superior reporter on T1‐weighted images and display highest contrast enhancement reported to‐date when using a clinical 3T MR scanner (≈21‐fold in vitro; ≈8‐fold in vivo). Stably expressing these hepatic transporters have no effect on human adipose derived mesenchymal stem cells (hADSCs) characteristics. However, only OATP1B3 able to trace as few as 2 × 105 hADSCs intramuscular xenograft survival time on NIR and 3T MRI. These data suggest that OATP1B3 is relatively a robust Gd‐EOB‐DTPA/ICG‐dependent multimodality reporter in visualizing dynamic processes for cell‐based therapies.
Clinical imaging is indispensable for measuring the safety and efficacy of cell‐based therapy. However, the ability to trace long‐term fate of transplanted cells with current technologies is limited. This article demonstrates human hepatocyte transporters as multimodal gene reporters, as these transporters can specifically uptake variety of clinically approved fluorescent, bioluminescent, and magnetic resonance imaging compounds.
BACKGROUNDBlood flow signals may be a confounder in quantifying T1 values of plaque or thrombus and how to realize black-blood T1 mapping remains a challenge task.PURPOSETo develop a fast and ...three-dimensional black-blood T1 mapping technique for quantitative assessment of atherosclerosis and venous thrombosis.STUDY TYPESequence development and optimization via phantoms and volunteers as well as pilot prospective.PHANTOM AND SUBJECTSNumerical simulations, a standard phantom, 8 healthy volunteers (mean age, 22 ± 1 years; 5 males), and 19 patients (mean age, 57 ± 14 years; 13 males) with atherosclerosis or venous thrombosis.FIELD STRENGTH/SEQUENCE3T/inversion recovery spin-echo sequence (IR-SE), magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE), and black-blood prepared MP2RAGE (BB-MP2RAGE).ASSESSMENTThe black-blood preparation (i.e., delay alternating with nutation for tailored excitation, DANTE) was incorporated into MP2RAGE for black-blood T1 mapping. The BB-MP2RAGE was optimized numerically based on the Bloch equation, and then the phantom study was performed to verify the accuracy of T1 mapping by BB-MP2RAGE against IR-SE and MP2RAGE. Preliminary clinical validation was prospectively performed to assess the flow suppression effect and its potential application in plaque and thrombosis identification.STATISTICAL TESTSPearson correlation test, Bland-Altman analysis, paired t-test, and intraclass correlation coefficient. A P value <0.05 indicates a statistically significant difference.RESULTSPhantom experiments showed comparable accuracy of T1 maps by BB-MP2RAGE with IR-SE and MP2RAGE (all r2 > 0.99); Compared to MP2RAGE, BB-MP2RAGE effectively nulled the blood flow signals, and had a significant improvement in contrast-to-noise ratio between static tissue and blood (250.5 ± 66.6 vs. 91.9 ± 35.9). BB-MP2RAGE can quantify plaque or thrombus T1 relaxation time with blood flow signal suppression.DATA CONCLUSIONAccurate T1 mapping with sufficient blood flow suppression was achieved by BB-MP2RAGE. BB-MP2RAGE has the potential to quantitatively characterize atherosclerosis and venous thrombosis.LEVEL OF EVIDENCE1 TECHNICAL EFFICACY: Stage 1.
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