Gadolinium deposition in the liver and brain in a rat model with liver fibrosis after intravenous administration of gadoxetate disodium.

Objectives: To investigate gadolinium deposition in the liver and brain in a rat model with liver fibrosis (LF) after intravenous administration of gadoxetate disodium (GD) and the histological effects of gadolinium deposition in the liver and brain. Methods: Adult male Sprague-Dawley rats were randomly assigned to one of the three groups: 1) LF group received intraperitoneal injection of carbon tetrachloride (CCl4) for 9 weeks alone; 2) LF&GD group received CCl4 and intravenous administration of GD (for 5 consecutive days); 3) GD group received olive oil and GD. Seven days after the final injection of GD, the deep cerebellar nuclei (DCN) and liver were excised to determine gadolinium concentrations via inductively coupled plasma mass spectrometry, and histologic staining was performed. Bonferroni's post-hoc test and Wilcoxon rank sum test were used to compare the differences between the three groups. Results: The concentrations of retained gadolinium in the liver in the LF&GD group (2.18 ± 0.44 µg/g) were significantly greater compared to the LF group (0.02 ± 0.01 µg/g, P < 0.001) and GD group (0.37 ± 0.11 µg/g, P < 0.001). Also, the concentrations of retained gadolinium in DCN were increased in the LF&GD group (0.13 ± 0.06 µg/g) compared to the LF group (0.01 ± 0.00 µg/g, P < 0.001) and GD group (0.06 ± 0.02 µg/g, P = 0.019). No histopathological alterations were detected in the liver and DCN between LF&GD group and LF group. Conclusions: LF aggravated gadolinium deposition in the liver and DCN after administration of GD. However, no significant acute histological alterations were observed due to gadolinium deposition.

The effects of flip angle and gadolinium contrast agent on single breath-hold compressed sensing cardiac magnetic resonance cine for biventricular global strain assessment.

Background: Due to its potential to significantly reduce scanning time while delivering accurate results for cardiac volume function, compressed sensing (CS) has gained traction in cardiovascular magnetic resonance (CMR) cine. However, further investigation is necessary to explore its feasibility and impact on myocardial strain results. Materials and methods: A total of 102 participants [75 men, 46.5 ± 17.1 (SD) years] were included in this study. Each patient underwent four consecutive cine sequences with the same slice localization, including the reference multi-breath-hold balanced steady-state free precession (bSSFPref) cine, the CS cine with the same flip angle as bSSFPref before (CS45) and after (eCS45) contrast enhancement, and the CS cine (eCS70) with a 70-degree flip angle after contrast enhancement. Biventricular strain parameters were derived from cine images. Two-tailed paired t-tests were used for data analysis. Results: Global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain (GLS) were observed to be significantly lower in comparison to those obtained from bSSFPref sequences for both the right and left ventricles (all p < 0.001). No significant difference was observed on biventricular GRS-LAX (long-axis) and GLS values derived from enhanced and unenhanced CS cine sequences with the same flip angle, but remarkable reductions were noted in GRS-SAX (short-axis) and GCS values (p < 0.001). After contrast injection, a larger flip angle caused a significant elevation in left ventricular strain results (p < 0.001) but did not affect the right ventricle. The increase in flip angle appeared to compensate for contrast agent affection on left ventricular GRS-SAX, GCS values, and right ventricular GRS-LAX, GLS values. Conclusion: Despite incorporating gadolinium contrast agents and applying larger flip angles, single breath-hold CS cine sequences consistently yielded diminished strain values for both ventricles when compared with conventional cine sequences. Prior to employing this single breath-hold CS cine sequence to refine the clinical CMR examination procedure, it is crucial to consider its impact on myocardial strain results.

Integrin-Targeted Theranostic Nanoparticles for Clinical MRI-Traceable Treatment of Liver Fibrosis.

Liver fibrosis is the critical stage in the development of chronic liver disease (CLD), from simple injury to irreversible cirrhosis. Timely detection and intervention of liver fibrosis are crucial for preventing CLD from progressing into a fatal condition. Herein, we developed iron oxide (Fe3O4) nanoparticles (IONPs) and ferulic acid (FA) coencapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), followed by surface modification with cRGD peptides (cRGD-PLGA/IOFA) for integrin-targeted clinical magnetic resonance imaging (MRI)-traceable treatment of liver fibrosis. The cRGD peptide linked on the surface of the PLGA/IOFA NPs could specifically bind to the overexpressed integrin αvß3 on activated hepatic stellate cells (HSCs) in the fibrotic liver, enabling the high-sensitive clinical MR imaging (3 T) and precise staging of liver fibrosis. The FA encapsulated in cRGD-PLGA/IOFA showed excellent efficacy in reducing oxidative stress and inhibiting the activation of HSCs through the transforming growth factor-ß (TGF-ß)/Smad pathway. Notably, the IONPs encapsulated in cRGD-PLGA/IOFA NPs could alleviate liver fibrosis by regulating hepatic macrophages through the NF-κB pathway, lowering the proportion of Ly6Chigh/CD86+, and degrading collagen fibers. The FA and IONPs in the cRGD-PLGA/IOFA produced a synergistic enhancement effect on collagen degradation, which was more effective than the IONPs treatment alone. This study demonstrates that cRGD-PLGA/IOFA NPs could effectively relieve liver fibrosis by acting on macrophages and HSCs and provide a new strategy for the clinical MRI-traceable treatment of liver fibrosis.

Supramolecular metal-organic frameworks as host-guest nanoplatforms for versatile and customizable biomedical applications.

Molecular imaging of disease with multifunctional nanoparticles has improved specificity and sensitivity but also raises the complexity, potential toxicity, and cost. Here, we show a facile and degradable self-assembly ß-cyclodextrin metal-organic framework (ß-CD-MOF) nanoplatform for customizable multifunctional imaging. These ß-CD-MOF nanoparticles were obtained with favorable morphology and size by controlling the degradation time. The ß-CD-MOF were used as nanoplatforms for facile functionalization with adamantane (Ad)-modified probes through host-guest interactions between the surface ß-CD units and Ad molecules. We demonstrated the method's feasibility and capability by developing various contrast agents for multiple biomedical imaging, including fluorescence imaging, magnetic resonance imaging (MRI), and computed tomography (CT) imaging. The nanoprobes showed superior performance compared to the corresponding small molecular probes, including better physio-chemical properties (e.g., about 5 times of T1 relaxivity for MRI, 1.2 times of Hounsfield units for CT), improved pharmacokinetics, effective tissue imaging capability, and low safety concerns. These ß-CD-MOF-based nanoparticles are promising host-guest nanoplatforms for developing multifunctional and safe imaging probes. STATEMENT OF SIGNIFICANCE: Molecular imaging of disease with multifunctional nanoparticles has improved specificity and sensitivity but also raises the complexity, potential toxicity, and cost. Here, we introduce facile and degradable self-assembly ß-cyclodextrin metal-organic framework (ß-CD-MOF) nanoplatforms for customizable multifunctional imaging. The significance of this work includes: 1) This work reports the tailoring of MOFs nanoparticles with suitable sizes and shapes for biomedical applications through controllable morphological transition and degradation; 2) The ß-CD-MOF-based host-guest nanoplatforms are facile and feasible for developing multifunctional nanoparticular contrast agents for effective tissue imaging; 3) The nanoparticular contrast agents show low safety concerns with a long-term tissue deposition similar to the small molecular probes.

Real-Time Objective Evaluation of the Ischemic Stroke through pH-Responsive Fluorescence Imaging.

A rapid and comprehensive assessment of ischemic stroke (IS) is critical for clinicians to take the most appropriate treatment. Currently, IS assessment is mainly carried out by computed tomography and magnetic resonance imaging in combination with observing the clinical symptoms and inquiring about contraindications. However, they cannot diagnose pathological conditions and judge the microenvironment in real-time. Near-infrared fluorescence imaging has advantages for IS imaging, such as high sensitivity, high spatiotemporal resolution, and straightforward real-time operation. Herein, a pH-responsive fluorescent liposomal probe (BOD@Lip) is prepared for in vivo real-time visualization of the degree of IS based on the different acid microenvironments in the progression of the disease. The fluorescence imaging with BOD@Lip shows the degree of IS, and the correlation between fluorescence signals and the neurological deficit scores is established for the first time. This work provides a new method to objectively evaluate the degree of IS through a visualized route and a new insight into the relationship between the acidic microenvironment and the progression of IS.

Identification of fibrosis in hypertrophic cardiomyopathy: a radiomic study on cardiac magnetic resonance cine imaging.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) often requires repeated enhanced cardiac magnetic resonance (CMR) imaging to detect fibrosis. We aimed to develop a practical model based on cine imaging to help identify patients with high risk of fibrosis and screen out patients without fibrosis to avoid unnecessary injection of contrast. METHODS: A total of 273 patients with HCM were divided into training and test sets at a ratio of 7:3. Logistic regression analysis was used to find predictive image features to construct CMR model. Radiomic features were derived from the maximal wall thickness (MWT) slice and entire left ventricular (LV) myocardium. Extreme gradient boosting was used to build radiomic models. Integrated models were established by fusing image features and radiomic models. The model performance was validated in the test set and assessed by ROC and calibration curve and decision curve analysis (DCA). RESULTS: We established five prediction models, including CMR, R1 (based on the MWT slice), R2 (based on the entire LV myocardium), and two integrated models (ICMR+R1 and ICMR+R2). In the test set, ICMR+R2 model had an excellent AUC value (0.898), diagnostic accuracy (89.02%), sensitivity (92.54%), and F1 score (93.23%) in identifying patients with positive late gadolinium enhancement. The calibration plots and DCA indicated that ICMR+R2 model was well-calibrated and presented a better net benefit than other models. CONCLUSIONS: A predictive model that fused image and radiomic features from the entire LV myocardium had good diagnostic performance, robustness, and clinical utility. KEY POINTS: • Hypertrophic cardiomyopathy is prone to fibrosis, requiring patients to undergo repeated enhanced cardiac magnetic resonance imaging to detect fibrosis over their lifetime follow-up. • A predictive model based on the entire left ventricular myocardium outperformed a model based on a slice of the maximal wall thickness. • A predictive model that fused image and radiomic features from the entire left ventricular myocardium had excellent diagnostic performance, robustness, and clinical utility.

Novel manganese and polyester dendrimer-based theranostic nanoparticles for MRI and breast cancer therapy.

Therapeutic nanoplatforms are widely used in the diagnosis and treatment of breast cancer due to the merits of enabling high soft-tissue resolution and the availability of numerous therapeutic nanoparticles. It is thus vital to develop multifunctional theranostic nanoparticles for the visualization and dynamic monitoring of tumor therapy. In this study, we designed a manganese-based and hypericin-loaded polyester dendrimer nanoparticle (MHD) for magnetic resonance imaging (MRI) and hypericin-based photodynamic therapy (PDT) enhancement. We found that MHD could greatly enhance MRI contrast with a longitudinal relaxivity of 5.8 mM-1 s-1 due to the Mn-based paramagnetic dendrimer carrier. Meanwhile, the MRI-guided PDT inhibition of breast tumors could be achieved by the hypericin-carrying MHD and further improved by Mn2+-mediated alleviation of the hypoxic microenvironment and the enhancement of cellular ROS. Besides, MHD showed excellent biocompatibility and biosafety with liver and kidney clearance mechanisms. Thus, the high efficiency in MRI contrast enhancement and excellent tumor-inhibiting effects indicate MHD's potential as a novel, stable, and multifunctional nanotheranostic agent for breast cancer.

Nomogram based on prognostic nutrition index and Chest CT imaging signs predicts lymph node metastasis in NSCLC patients.

OBJECTIVE: To establish and validate a model capable of predicting lymph node metastasis (LNM) of non-small cell lung cancer (NSCLC) patients. METHODS: Preoperative clinical and CT imaging data on patients with NSCLC undergoing surgery were retrospectively analyzed. A model was developed using a training cohort of 290 patients. The univariate analysis followed by dichotomous logistic regression was performed to estimate different risk factors of lymph node metastasis, and a nomogram was constructed. Using another testing cohort of 120 patients, the performance of the nomogram was validated using several evaluation methods and indices and evaluated including via the area under the curve (AUC), calibration curve, Hosmer-Lemeshow test and decision curve analysis (DCA). RESULTS: CT-based imaging signs were important independent risk factors for lymph node metastasis in NSCLC patients. The possible risk factors also included four other independent risk factors through dichotomous logistic regression, i.e., age, SIRI, PNI and CEA, which were filtered and included in the nomogram. Nomogram yields AUC values of 0.828 [95% confidence interval (CI): 0.778-0.877] in the training cohort and 0.816 (95% CI: 0.737-0.895) in the validation cohort, respectively. The calibration curves showed high agreement in both the training and validation cohorts. At the threshold probability of 0-0.8, the nomogram increases the net outcomes compared to the treat-none and treat-all lines in the decision curve. CONCLUSIONS: The nomogram based on the PNI and CT images signs holds promise as a novel and accurate tool for predicting the LNM in NSCLC patients and guiding intraoperative lymph node dissection.

A Risk Score to Diagnose Cardiac Involvement and Provide Prognosis Information in Patients at Risk of Cardiac Light-Chain Amyloidosis.

Background: Cardiac light-chain amyloidosis (AL CA) portends poor prognosis. Contrast cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) imaging is an important tool in recognizing AL CA. But contraindications to contrast CMR would significantly restrict its clinical application value. Our study aims to construct a convenient risk score to help identify cardiac involvement in patients at risk of AL CA. Moreover, we also investigate whether this risk score could provide prognosis information. Materials and Methods: Sixty-three patients at risk of AL CA were retrospectively included in our study. Basic clinical characters, lab results, 12-lead electrocardiogram data, and cardiac magnetic resonance image data were collected. AL CA was diagnosed according to typical CA LGE pattern. Logistic analysis was used to figure out predictive parameters of AL CA and their ß coefficients, further constructing the risk score. Receiver operating characteristics (ROC) curve was used to find the cut-off point best distinguishing AL CA+ from AL CA-patients. Bootstrapping was used for internal validation. All patients were divided into high-risk and low-risk group according to the diagnostic cut-off point, and followed up for survival information. Kaplan-Meier plots and log-rank test were performed to analyze if this score had prognostic value. Results: The risk score finally consisted of 4 parameters: pericardial effusion (PE) (1 point), low electrocardiographic QRS voltages (LQRSV) (1 point), CMR-derived impaired global radial strain (GRS) (<15.14%) (1 point) and increased left ventricular maximum wall thickness (LVMWT) (>13 mm) (2 points). Total score ranged from 0 to 5 points. A cut-off point of 1.5 showed highest accuracy in diagnosing AL CA with an AUC of 0.961 (95% CI: 0.924-0.997, sensitivity: 90.6%, specificity: 83.9%). Kaplan-Meier plots and log-rank test showed that the high-risk group had significantly poor overall survival rates. Conclusion: In patients at risk of AL CA, a risk score incorporating the presence of PE, LQRSV, and CMR-derived impaired GRS and increased LVMWT is predictive of a diagnosis of AL CA by LGE criteria. This risk score may be helpful especially when contrast CMR is not available or contraindicated, and further studies should be considered to validate this score.

Global Circumferential Strain by Cardiac Magnetic Resonance Tissue Tracking Associated With Ventricular Arrhythmias in Hypertrophic Cardiomyopathy Patients.

Background: Hypertrophic cardiomyopathy (HCM) is prone to myocardial heterogeneity and fibrosis, which are the substrates of ventricular arrhythmias (VAs). Cardiac magnetic resonance tissue tracking (CMR-TT) can quantitatively reflect global and regional left ventricular strain from different directions. It is uncertain whether the change of myocardial strain detected by CMR-TT is associated with VAs. The aim of the study is to explore the differential diagnostic value of VAs in HCM by CMR-TT. Materials and Methods: We retrospectively included 93 HCM patients (38 with VAs and 55 without VAs) and 30 healthy cases. Left ventricular function, myocardial strain parameters and percentage of late gadolinium enhancement (%LGE) were evaluated. Results: Global circumferential strain (GCS) and %LGE correlated moderately (r = 0.51, P < 0.001). HCM patients with VAs had lower left ventricular ejection fraction (LVEF), global radial strain (GRS), GCS, and global longitudinal strain (GLS), but increased %LGE compared with those without VAs (P < 0.01 for all). %LGE and GCS were indicators of VAs in HCM patients by multivariate logistic regression analysis. HCM patients with %LGE >5.35% (AUC 0.81, 95% CI 0.70-0.91, P < 0.001) or GCS >-14.73% (AUC 0.79, 95% CI 0.70-0.89, P < 0.001) on CMR more frequently had VAs. %LGE + GCS were able to better identify HCM patients with VAs (AUC 0.87, 95% CI 0.79-0.95, P < 0.001). Conclusion: GCS and %LGE were independent risk indicators of VAs in HCM. GCS is expected to be a good potential predictor in identifying HCM patients with VAs, which may provide important values to improve risk stratification in HCM in clinical practice.

Diffusion tensor imaging in evaluating testicular injury after unilateral testicular torsion and detorsion in rat model: A preliminary study.

Diffusion tensor imaging (DTI) is a functional magnetic resonance sequence based on the movement of water molecules. This study attempted to investigate the feasibility of DTI in evaluating testicular injury after testicular torsion and detorsion. Seventy-two rats were randomly divided into the sham group, torsion group and detorsion group. The left testis in the sham group was brought out through a scrotal incision for 1 hr, and that of the torsion group was twisted 720o clockwise for 1 hr and fixed to the scrotum, while the detorsion group was restored after being twisted 720° for 1 hr. Rats were further divided into four subgroups according to the set time, then performed DTI and histology analysis. The mean diffusion of the torsion and detorsion groups increased within 24 hr (p <.01), while it in the detorsion-1-week-group was lower than that in the detorsion-24-hr-group (p <.05). The fraction anisotropy of both experimental groups decreased in the acute phase (p <.01), while that of the detorsion-1-week-group increased (p <.01). Cosentino score in both experimental groups showed an increasing trend (p <.05). Besides, the spermatogenic ability of the detorsion-1-week-group decreased (p <.05). In conclusion, DTI was able to evaluate the injury after testicular torsion and detorsion.

Self-assembly of hyaluronic acid-mediated tumor-targeting theranostic nanoparticles.

Theranostic nanoparticles (NPs) have emerged as promising candidates for cancer diagnosis and treatment. Manganese dioxide (MnO2)-based NPs are potential contrast agents with excellent paramagnetic property and biocompatibility, exhibiting satisfactory magnetic resonance imaging (MRI) effects and biological safety. Recently, hyaluronic acid (HA) has gained increasing interest due to its tumor-targeting ability, which can improve the tumor affinity of manganese dioxide (MnO2)-based NPs. In this study, HA-coated and albumin (BSA)-templated MnO2 and polydopamine hybrid nanoparticles (HMDNs) with tumor-targeting and superior imaging capability were fabricated via modifying the nanoparticles prepared by integrating dopamine polymerization and MnO2 biomineralization. The modification was found to enhance the cellular uptake of HMDNs by cancer cells. The prepared HMDN had high MRI contrasting capability with a longitudinal relaxivity of 22.2 mM-1 s-1 and strong photothermal therapy (PTT) effects with nearly complete tumor ablation under laser irradiation in vivo. HMDNs also showed effective clearance through kidneys, with no toxicity to important tissues. Therefore, HMDNs with superior imaging and PTT capability presented a new method to prepare tumor-targeting multifunctional nanotheranostics.

A linear stepping endovascular intervention robot with variable stiffness and force sensing.

BACKGROUND/PURPOSE: Robotic-assisted endovascular intervention surgery has attracted significant attention and interest in recent years. However, limited designs have focused on the variable stiffness mechanism of the catheter shaft. Flexible catheter needs to be partially switched to a rigid state that can hold its shape against external force to achieve a stable and effective insertion procedure. Furthermore, driving catheter in a similar way with manual procedures has the potential to make full use of the extensive experience from conventional catheter navigation. Besides driving method, force sensing is another significant factor for endovascular intervention. METHODS: This paper presents a variable stiffness catheterization system that can provide stable and accurate endovascular intervention procedure with a linear stepping mechanism that has a similar operation mode to the conventional catheter navigation. A specially designed shape-memory polymer tube with water cooling structure is used to achieve variable stiffness of the catheter. Hence, four FBG sensors are attached to the catheter tip in order to monitor the tip contact force situation with temperature compensation. RESULTS: Experimental results show that the actuation unit is able to deliver linear and rotational motions. We have shown the feasibility of FBG force sensing to reduce the effect of temperature and detect the tip contact force. The designed catheter can change its stiffness partially, and the stiffness of the catheter can be remarkably increased in rigid state. Hence, in the rigid state, the catheter can hold its shape against a [Formula: see text] load. The prototype has also been validated with a vascular phantom, demonstrating the potential clinical value of the system. CONCLUSION: The proposed system provides important insights into the design of compact robotic-assisted catheter incorporating effective variable stiffness mechanism and real-time force sensing for intraoperative endovascular intervention.