Constructing Multiscroll Memristive Neural Network With Local Activity Memristor and Application in Image Encryption.

Memristor possesses synapse-like properties that can mimic excitation and inhibition between neurons. This article introduces the Sigmoid functions to the memristor and constructs a new memristive Hopfield neural network (HNN). Its most distinctive feature is the simple topology, which contains only unidirectional connections in neurons. The equilibrium points analysis reveals the mechanism of its multiscroll attractors generation. Homogeneous and heterogeneous coexisting attractors are observed with the variation of the network parameters. Note that the state equation of memristor can affect the number of coexisting attractors. A hardware implementation is designed for it, and the multiscroll attractors are captured in the oscilloscope. Finally, it is also applied to developing an image encryption algorithm with excellent performance.

Overcoming challenges in the delivery of STING agonists for cancer immunotherapy: A comprehensive review of strategies and future perspectives.

STING (Stimulator of Interferon Genes) agonists have emerged as promising agents in the field of cancer immunotherapy, owing to their excellent capacity to activate the innate immune response and combat tumor-induced immunosuppression. This review provides a comprehensive exploration of the strategies employed to develop effective formulations for STING agonists, with particular emphasis on versatile nano-delivery systems. The recent advancements in delivery systems based on lipids, natural/synthetic polymers, and proteins for STING agonists are summarized. The preparation methodologies of nanoprecipitation, self-assembly, and hydrogel, along with their advantages and disadvantages, are also discussed. Furthermore, the challenges and opportunities in developing next-generation STING agonist delivery systems are elaborated. This review aims to serve as a reference for researchers in designing novel and effective STING agonist delivery systems for cancer immunotherapy.

Recent advances in small molecular near-infrared fluorescence probes for a targeted diagnosis of the Alzheimer disease.

Nowadays, it is still quite challenging to achieve an early diagnosis of the Alzheimer disease (AD) in clinics. The burgeoning near-infrared fluorescence (NIRF) imaging fulfills the requirements for a precise diagnosis with good sensitivity and a high signal-to-background ratio and offers opportunities for the efficient AD diagnosis. As the pathogenesis of AD is quite complex, there is an ongoing exploration of advanced probes to specifically target AD biomarkers (e.g., amyloid-ß (Aß) plaques, neurofibrillary tangles, viscosity, peroxynitrite (ONOO-), reactive oxygen species, and methylglyoxal). To this end, a great number of small molecular fluorescent probes with good water solubility, blood-brain barrier crossing capability, and ease in tuning photophysical and biological properties have been studied for the AD diagnosis. Herein, we systematically update the progress of NIRF AD probes in the last three years. The special focus is on the mechanisms for the targeted diagnosis and the relationship between the structure and properties of the probes. Importantly, NIRF probes with complementary functions such as dual-responsiveness and multimodal imaging and even therapeutics are discussed. Moreover, the challenges and perspectives of the AD probes are briefly elucidated. We hope that this review provides guidance for researchers and expedites the preclinical and clinical study of the NIRF AD probes.

Recent development of contrast agents for magnetic resonance and multimodal imaging of glioblastoma.

Glioblastoma (GBM) as the most common primary malignant brain tumor exhibits a high incidence and degree of malignancy as well as poor prognosis. Due to the existence of formidable blood-brain barrier (BBB) and the aggressive growth and infiltrating nature of GBM, timely diagnosis and treatment of GBM is still very challenging. Among different imaging modalities, magnetic resonance imaging (MRI) with merits including high soft tissue resolution, non-invasiveness and non-limited penetration depth has become the preferred tool for GBM diagnosis. Furthermore, multimodal imaging with combination of MRI and other imaging modalities would not only synergistically integrate the pros, but also overcome the certain limitation in each imaging modality, offering more accurate morphological and pathophysiological information of brain tumors. Since contrast agents contribute to amplify imaging signal output for unambiguous pin-pointing of tumors, tremendous efforts have been devoted to advances of contrast agents for MRI and multimodal imaging. Herein, we put special focus on summary of the most recent advances of not only MRI contrast agents including iron oxide-, manganese (Mn)-, gadolinium (Gd)-, 19F- and copper (Cu)-incorporated nanoplatforms for GBM imaging, but also dual-modal or triple-modal nanoprobes. Furthermore, potential obstacles and perspectives for future research and clinical translation of these contrast agents are discussed. We hope this review provides insights for scientists and students with interest in this area.

Usefulness of diffusion derived vessel density computed from a simplified IVIM imaging protocol: An experimental study with rat biliary duct blockage induced liver fibrosis.

OBJECTIVES: Liver vessel density can be evaluated by DDVD (diffusion derived vessel density): DDVD(b0b1) = Sb0/ROIarea0 - Sb1/ROIarea1, where Sb0 and Sb1 refer to the liver signal when b is 0 or 1 s/mm2. Sb1 and ROIarea1 may be replaced by other b-values. With a rat biliary duct ligation (BDL) model, this study assesses the usefulness of liver DDVD computed from a simplified IVIM imaging protocol using b = 25 and b = 50 to replace b = 1 s/mm2, alone and in combination with other IVIM parameters. METHODS: Male Sprague-Dawley rats were used. The rat number was 5, 5, 5, and 3 respectively, for the timepoints of 7, 14, 21, 28 days post-BDL surgery. 12 rats had partial biliary duct recanalization performed after the rats had BDL for 7 days and then again followed-up for a mean of 14 days. Liver diffusion MRIs were acquired at 3.0 T with a b-value distribution of 0, 25, 50, 75, 100, 150, 300, 700, 1000 s/mm2. DDVDmean (control rats n = 6) was the mean of DDVD(b0b25) and DDVD(b0b50). IVIM fitting started from b = 0 s/mm2 with segmented fitting and a threshold b of 50 s/mm2 (n = 5 for control rats). Three 3-D spaces were constructed using a combination of the four diffusion parameters. RESULTS: The control rats and BDL rats (n = 18) had a liver DDVDmean of 84.0 ± 26.2 and 44.7 ± 14.4 au/pixel (p < 0.001). All 3-D spaces totally separated healthy livers and all fibrotic livers (n = 30, BDL rats and recanalization rats). The mean relative distance between healthy liver cluster and fibrotic liver cluster was 0.331 for PF, Dslow, and Dfast; 0.381 for PF, Dfast, and DDVDmean; and 0.384 for PF, Dslow, and DDVDmean. CONCLUSION: A combination of PF, Dslow, and Dfast allows total separation of healthy livers and fibrotic livers and the integration of DDVD improved the separation.

Comparison of T1 Mapping and T1rho Values with Conventional Diffusion-weighted Imaging to Assess Fibrosis in a Rat Model of Unilateral Ureteral Obstruction.

RATIONALE AND OBJECTIVES: The aim of this study was to investigate the potential of magnetic resonance imaging (MRI) T1 mapping and T1 relaxation time in the rotating frame (T1rho) for assessment of renal fibrosis in a rat model of unilateral ureteral obstruction (UUO). MATERIALS AND METHODS: UUO was created in 36 rats. Six rats were scanned at each of the six time points (on days 0, 1, 3, 5, 10, and 15 after UUO). The contralateral kidneys were examined as controls. Hematoxylin-eosin, Masson's trichrome, and alpha-smooth muscle actin (α-SMA) antibody staining assays were performed. MRI data obtained with a 3.0T scanner were analyzed with α-SMA expression and Masson's staining. RESULTS: The T1 relaxation times and T1rho values increased, and the mean apparent diffusion coefficient (ADC) values decreased with time after UUO. Simple regression analysis indicated that the mean ADCs, T1 relaxation times, and T1rho values had strong correlations with the α-SMA expression levels (R2 = 0.34, R2 = 0.66, R2 = 0.71, respectively; P< .001) and positive Masson's staining (R2 = 0.38, R2 = 0.67, R2 = 0.65, respectively; P< .001). CONCLUSIONS: The T1 mapping and T1rho parameters had better correlations with α-SMA expression and Masson's staining than ADC values.

Intravoxel Incoherent Motion and Arterial Spin Labeling MRI Analysis of Reversible Unilateral Ureteral Obstruction in Rats.

BACKGROUND: Renal fibrosis is a common consequence of chronic kidney disease (CKD) and is the mechanism by which various forms of CKD progress to endstage renal failure. Accurate assessment of renal fibrosis is important for treatment. PURPOSE: To measure longitudinal changes of intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) before and after reversible unilateral ureteral obstruction in an animal model. STUDY TYPE: Self-controlled animal study. ANIMAL MODEL: Surgical obstruction of the ureters was performed and then removed after 5 days. Rats were scanned on Days 0, 1, 3, and 5 after creating the obstruction and on Days 4, 7, and 12 after releasing the obstruction. FIELD STRENGTH/SEQUENCE: 3.0T/IVIM/ASL. ASSESSMENT: The apparent diffusion coefficient (ADC), pure molecular diffusion (D), perfusion fraction (f), pseudodiffusion (D*), and renal blood flow (RBF) obtained from the ASL were measured. STATISTICAL TESTS: Using SPSS v. 20.0 software, P < 0.05 were considered statistically significant. The data from each timepoint were compared using one-way analysis of variance and correlation analysis was applied to various parameters. RESULTS: The postobstruction kidneys showed renal tubule swelling and increased collagen fiber content. Renal tubule swelling was relieved after reversing the obstruction, but Masson staining and cell density analysis revealed progressive changes that were primarily localized to the medulla. In general, ADC, D, f, D*, and RBF decreased with time during the 5 days of obstruction, and increased after release of the obstruction. ADC positively correlated with D, f, D*, and RBF (r = 0.415, r = 0.634, r = 0.465 r = 0.586, P < 0.001, respectively) in the cortex in this study. Also, ADC showed a positive correlation with D, f, and D* (r = 0.724, r = 0.749, r = 0.151, P < 0.001, respectively) in the medulla. DATA CONCLUSION: Kidney perfusion was the major factor affecting ADC. Functional imaging may be useful for following progression of CKD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:288-296.

Staging of rat liver fibrosis using monoexponential, stretched exponential and diffusion kurtosis models with diffusion weighted imaging- magnetic resonance.

Early diagnosis of liver fibrosis is important. The objective of this study was to explore the characteristics and to assess the accuracy of monoexponential, stretched exponential models (SEM), and diffusion kurtosis imaging (DKI) with diffusion-weighted imaging (DWI)-magnetic resonance imaging (MRI) in various stages of liver fibrosis in two standard rat models induced by carbon tetrachloride (CCl4) and biliary duct ligation (BDL). Parameters (ADC, Dapp, Kapp, DDC, α) were measured with a 3.0T MRI. Liver fibrosis stages (F0-F4) were defined by METAVIR scoring. Parameters (ADC, Dapp, DDC) were found to be negatively associated (r: -0.675~-0.789; P<0.05) with advancement of fibrosis stage. The analysis of receiver operating characteristic (ROC) curves illustrated that the areas under the curves (AUC) for ADC, Dapp, and DDC were 0.687~0.957, 0.805~0.938 and 0.876~1.000, respectively. The study showed that (ADC, Dapp, Kapp, DDC, α) from various diffusion models reflected pathological and physiological tissue changes. We conclude that SEM and DKI may provide more accurate information about diffusion, and non-Gaussian diffusion analysis may be a complementary tool for the assessment of liver fibrosis.

Assessment of liver fibrosis in rats by MRI with apparent diffusion coefficient and T1 relaxation time in the rotating frame.

PURPOSE: To explore the value of T1 relaxation times in the rotating frame (T1 ρ or T1 rho) for evaluating liver fibrosis stage, compared to apparent diffusion coefficients (ADCs). MATERIALS AND METHODS: Liver fibrosis in model rats (n = 50) was produced by carbon tetrachloride (CCl4 ) injection. Five rats died during the experiment. Surviving model rats (n = 45) and controls (n = 15) were subjected to 3.0T MRI and the ADCs (b-values: 0, 800 s/mm(2) ) and T1 ρ values were determined. Liver fibrosis stage (F0-F4) was defined based on METAVIR scoring. Nonparametric statistical methods and receiver operating characteristic (ROC) curve analyses were employed to determine diagnostic accuracy. RESULTS: Mean ADC and T1 ρ associated negatively (r = -0.732 P < 0.001) and positively (r = 0.863 P < 0.001), respectively, with severity of fibrosis stage. Analysis of ROC curves for fibrosis staging showed that the area under the curve (AUC) for T1 ρ (stage F0 vs. F1-F4 = 0.976, stage F0-F1 vs. F2-F4 = 0.920, stage F0-F2 vs. F3-F4 = 0.938, and stage F0-F3 vs. F4 = 0.931) was larger than that for ADCs (0.917, 0.924, 0.842, and 0.781, respectively). CONCLUSION: ADC and T1 ρ values correlate with liver fibrosis stage. The performance of the T1 ρ parameter was superior to that of the ADC parameter in the differentiation of liver fibrosis stages in a CCl4 rat model.

Intravoxel incoherent motion MRI evaluation for the staging of liver fibrosis in a rat model.

PURPOSE: To explore the characteristics of intravoxel incoherent motion (IVIM) in various stages of liver fibrosis, and their relationships with fibrotic stages in rats. MATERIALS AND METHODS: Fifty rats were given various doses of carbon tetrachloride (CCl4 ) to induce various fibrotic stages in rats; 15 untreated rats served as controls. Diffusion-weighted magnetic resonance imaging (MRI) was performed and eight b-values (0-800 s/mm(2) ) were applied to obtain IVIM parameters (D, pure molecular diffusion; f, perfusion fraction; D*, pseudodiffusion). The stages of liver fibrosis (stages F0-F4) were evaluated histologically using METAVIR scores. Fifty-seven rats (15 controls and 42 with fibrosis) were analyzed by nonparametric methods and receiver operating characteristic curves to determine diagnostic accuracy. RESULTS: Significant differences (P < 0.001) were found between stages (stages F0-F4) by D, f, D*, and apparent diffusion coefficient (ADC). There were inverse correlations between fibrosis stages and D, f, D*, ADC (r = -0.657, r = -0.631, r = -0.711 r = -0.719, respectively). Multivariate analysis showed that the combination models (D, f, D*) were better than the individual parameter (ADC) for the evaluation fibrosis stages (area under the curve [AUC]: 0.821-1.000 vs. AUC: 0.753-0.918) CONCLUSION: IVIM-derived parameters showed significant correlations with stages of liver fibrosis in a rat model.