ABSTRACT
Purpose: To use hepatic uptake index (HUI) of liver lobes on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) to discriminate between patients with hepatitis B-related cirrhosis in compensated and decompensated statuses. Methods: Forty-four consecutive patients with hepatitis B-related cirrhosis who underwent Gd-EOB-DTPA-enhanced MRI were divided into compensated and decompensated statuses based on clinical evaluation. Volume and signal intensity of individual lobes were retrospectively measured to calculate HUI of the right liver lobe (RHUI), medial (MHUI) and lateral (LHUI) left liver lobes, and caudate lobe (CHUI). Spearman's rank correlation analyses were performed to evaluate relationships of lobe-based HUI with Child-Pugh and model for end-stage liver disease (MELD) scoring system scores in compensated and decompensated statuses. The Mann-Whitney U-test was used to compare the lobe-based HUI between compensated and decompensated statuses. The performance of lobe-based HUI in distinguishing cirrhosis was evaluated using receiver operating characteristic (ROC) analysis, and the area under the ROC curve (AUC) was calculated as a measure of accuracy. Delong's method was used for statistical analysis to elucidate which HUI is optimal. Results: Compensated and decompensated liver cirrhosis were confirmed in 25 (56.82%) and 19 (43.18%) patients, respectively. According to Spearman's rank correlation analysis, RHUI, MHUI, LHUI, and CHUI were all significantly associated with Child-Pugh and MELD scores (all P values <0.05). Receiver operating characteristic analysis demonstrated that among all lobe-based HUI parameters, RHUI could best perform the previous discrimination with a cut-off of 485.73 and obtain an AUC of 0.867. The AUC of RHUI improved and was significantly different from that of MHUI, LHUI, and CHUI (P = 0.03, P = 0.007, and P < 0.001, respectively, Delong's test). Conclusions: The RHUI could help quantitatively discriminate hepatitis B-related cirrhosis between compensated and decompensated statuses.
Subject(s)
Contrast Media , Gadolinium DTPA , Liver Cirrhosis , Liver , Magnetic Resonance Imaging , Humans , Gadolinium DTPA/pharmacokinetics , Gadolinium DTPA/administration & dosage , Liver Cirrhosis/diagnostic imaging , Female , Male , Contrast Media/pharmacokinetics , Middle Aged , Magnetic Resonance Imaging/methods , Retrospective Studies , Liver/diagnostic imaging , Adult , ROC Curve , Aged , Severity of Illness Index , Hepatitis B/complications , Hepatitis B/diagnostic imagingABSTRACT
Manganese(II)-based contrast agents (MBCAs) are potential candidates for gadolinium-free enhanced magnetic resonance imaging (MRI). In this work, a rigid binuclear MBCA (Mn2-PhDTA2) with a zero-length linker was developed via facile synthetic routes, while the other dimer (Mn2-TPA-PhDTA2) with a longer rigid linker was also synthesized via more complex steps. Although the molecular weight of Mn2-PhDTA2 is lower than that of Mn2-TPA-PhDTA2, their T1 relaxivities are similar, being increased by over 71% compared to the mononuclear Mn-PhDTA. In the presence of serum albumin, the relaxivity of Mn2-PhDTA2 was slightly lower than that of Mn2-TPA-PhDTA2, possibly due to the lower affinity constant. The transmetalation reaction with copper(II) ions confirmed that Mn2-PhDTA2 has an ideal kinetic inertness with a dissociation half-life of approximately 10.4 h under physiological conditions. In the variable-temperature 17O NMR study, both Mn-PhDTA and Mn2-PhDTA2 demonstrated a similar estimated q close to 1, indicating the formation of monohydrated complexes with each manganese(II) ion. In addition, Mn2-PhDTA2 demonstrated a superior contrast enhancement to Mn-PhDTA in in vivo vascular and hepatic MRI and can be rapidly cleared through a dual hepatic and renal excretion pattern. The hepatic uptake mechanism of Mn2-PhDTA2 mediated by SLC39A14 was validated in cellular uptake studies.
Subject(s)
Contrast Media , Liver , Magnetic Resonance Imaging , Manganese , Manganese/chemistry , Liver/diagnostic imaging , Liver/metabolism , Magnetic Resonance Imaging/methods , Animals , Contrast Media/chemistry , Contrast Media/chemical synthesis , Humans , Cation Transport Proteins/metabolism , Cation Transport Proteins/chemistry , Mice , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesisABSTRACT
Non-invasive image-guided precise photothermal/photodynamic therapy (PTT/PDT) has been proven to be an effective local treatment modality but incompetent against metastases. Hence, the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication. Herein, a magnetic resonance imaging (MRI)-visualized PTT/PDT agent (SIDP NMs) was constructed, and the efficacy of its multimodal combination with a programmed cell death 1 (PD-1) inhibitor in the treatment of melanoma and metastases was studied. Due to the hydrophobic encapsulation of indocyanine green within the micellar core, SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under an 808 nm near-infrared laser. In vitro cell experiments showed that SIDP NMs had a good killing effect. After incubating with B16-F10 cells for 24 h and irradiating with an 808-nm laser for 10 min, cell viability decreased significantly. Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP non-invasively due to the presence of superparamagnetic iron oxide nanocrystal in SIDP NMs. When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI, the temperature of the tumor area rapidly increased from 32°C to 60.7°C in 5 min. In mouse melanoma ablation and distant tumor immunotherapy studies, SIDP NMs provided excellent MRI-guided PTT/PDT results and, when combined with PD-1 inhibitor, have great potential to cure primary tumors and eradicate metastases.
ABSTRACT
Considerable efforts have been made to develop nanoparticle-based magnetic resonance contrast agents (CAs) with high relaxivity. The prolonged rotational correlation time (τR) induced relaxivity enhancement is commonly recognized, while the effect of the water coordination numbers (q) on the relaxivity of nanoparticle-based CAs gets less attention. Herein, we first investigated the relationship between T1 relaxivity (r1) and q in manganese-based hybrid micellar CAs and proposed a strategy to enhance the relaxivity by increasing q. Hybrid micelles with different ratios of amphiphilic manganese complex (MnL) and DSPE-PEG2000 were prepared, whose q values were evaluated by Oxygen-17-NMR spectroscopy. Micelles with lower manganese doping density exhibit increased q and enhanced relaxivity, corroborating the conception. In vivo sentinel lymph node (SLN) imaging demonstrates that DSPE-PEG/MnL micelles could differentiate metastatic SLN from inflammatory LN. Our strategy makes it feasible for relaxivity enhancement by modulating q, providing new approaches for the structural design of high-performance hybrid micellar CAs.
Subject(s)
Micelles , Water , Manganese/chemistry , Lymphography , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy , Contrast Media/chemistryABSTRACT
Early diagnosis of osteoarthritis (OA) is critical for effective cartilage repair. However, lack of blood vessels in articular cartilage poses a barrier to contrast agent delivery and subsequent diagnostic imaging. To address this challenge, we proposed to develop ultra-small superparamagnetic iron oxide nanoparticles (SPIONs, 4 nm) that can penetrate into the matrix of articular cartilage, and further modified with the peptide ligand WYRGRL (particle size, 5.9 nm), which allows SPIONs to bind to type II collagen in the cartilage matrix and increase the retention of probes. Type II collagen in the cartilage matrix is gradually lost with the progression of OA, consequently, the binding of peptide-modified ultra-small SPIONs to type II collagen in the OA cartilage matrix is less, thus presenting different magnetic resonance (MR) signals in OA group from the normal ones. By introducing the AND logical operation, damaged cartilage can be differentiated from the surrounding normal tissue on T1 and T2 AND logical map of MR images, and this was also verified in histology studies. Overall, this work provides an effective strategy for delivering nanosized imaging agents to articular cartilage, which could potentially be used to diagnosis joint-related diseases such as osteoarthritis.
ABSTRACT
PURPOSE: Superparamagnetic iron oxide nanoparticles (SPION) are excellent magnetic resonance imaging (MRI) contrast agents. Mucin 4 (MUC4) acts as pancreatic cancer (PC) tumor antigen and influences PC progression. Small interfering RNAs (siRNAs) are used as a gene-silencing tool to treat a variety of diseases. METHODS: We designed a therapeutic probe based on polyetherimide-superparamagnetic iron oxide nanoparticles (PEI-SPION) combined with siRNA nanoprobes (PEI-SPION-siRNA) to assess the contrast in MRI. The biocompatibility of the nanocomposite, and silencing of MUC4 were characterized and evaluated. RESULTS: The prepared molecular probe had a particle size of 61.7 ± 18.5 nm and a surface of 46.7 ± 0.8mV and showed good biocompatibility in vitro and T2 relaxation efficiency. It can also load and protect siRNA. PEI-SPION-siRNA showed a good silencing effect on MUC4. CONCLUSION: PEI-SPION-siRNA may be beneficial as a novel theranostic tool for PC.
Subject(s)
Mucin-4 , Pancreatic Neoplasms , Humans , Mucin-4/genetics , Contrast Media , Magnetic Iron Oxide Nanoparticles , RNA, Small Interfering/genetics , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/therapyABSTRACT
Gadolinium (Gd)-based contrast agents (CAs) for clinical magnetic resonance imaging are facing the problems of low longitudinal relaxivity (r1) and toxicity caused by gadolinium deposition. Manganese-based small molecule complexes and manganese oxide nanoparticles (MONs) are considered as potential alternatives to Gd-based CAs due to their better biocompatibility, but their relatively low r1 values and complicated synthesis routes slow down their clinical translation. Herein, we presented a facile one-step co-precipitation method to prepare MONs using poly(acrylic acid) (PAA) as a coating agent (MnO2/PAA NPs), which exhibited good biocompatibility and high r1 values. A series of MnO2/PAA NPs with different particle sizes were prepared and the relationship between the particle size and r1 was studied, revealing that the MnO2/PAA NPs with a particle size of 4.9 nm exhibited higher r1. The finally obtained MnO2/PAA NPs had a high r1 value (29.0 Mn mM-1 s-1) and a low r2/r1 ratio (1.8) at 1.5 T, resulting in a strong T1 contrast enhancement. In vivo magnetic resonance angiography with Sprague-Dawley (SD) rats further proved that the MnO2/PAA NPs showed better angiographic performance at low-dosage administration than commercial Gadovist® (Gd-DO3A-Butrol). Moreover, the MnO2/PAA NPs could be rapidly cleared out after imaging, which effectively minimized the toxic side effects. The MnO2/PAA NPs are promising candidates for MR imaging of vascular diseases.
Subject(s)
Nanoparticles , Oxides , Rats , Animals , Magnetic Resonance Angiography , Manganese Compounds , Gadolinium , Rats, Sprague-Dawley , Contrast Media , Magnetic Resonance Imaging/methodsABSTRACT
Nanophotothermal agents that provide efficient and precise treatment at tumor sites are attracting increasing attention in biomedicine. In particular, the method combination of nanophotothermal agents and magnetic resonance imaging (MRI) shows great promise for biomedical therapeutic applications. Herein, a simple nanophotothermal agent with dopamine multivalent-modified polyaspartic acid chelated superparamagnetic iron oxide (SPIO) and ferric ion (SPIO@PAsp-DAFe/PEG) was developed for MRI-guided near-infrared photothermal therapy (PTT). SPIO@PAsp-DAFe/PEG was random SPIO nanocluster with good water solubility, had a diameter of 57.8 ± 7.8 nm in dynamic light scattering, negatively charged surface (zeta potential = -11 mV), exhibited good stability and outstanding photothermal conversion efficiency (35.4%) and produced superior magnetic resonance enhanced imaging. In the experiment with tumor-bearing mice, the MRI not only monitored the accumulation of SPIO@PAsp-DAFe/PEG nanocomposites enhanced by near-infrared irradiation after intravenous administration but also determined the appropriate time window for PTT. With the use of MRI-guided near-infrared therapy, the SPIO@PAsp-DAFe/PEG nanocomposites provided excellent therapeutic effects, confirming their great potential as effective MRI/PTT therapeutic agents.
ABSTRACT
Compared to traditional branched polymers with Gd(III) chelates conjugated on their surface, branched polymers with Gd(III) chelates as the internal skeleton are considered to be a reasonable strategy for preparing efficient magnetic resonance imaging contrast agents. Herein, the Gd(III) ligand DOTA was chosen as the internal skeleton; four different molecular weights (3.5, 5.3, 8.6, and 13.1 kDa) and degrees of branching poly-DOTA branched polymers (P1, P2, P3, and P4) were synthesized by a simple "A2 + B4"-type one-pot polymerization. The Gd(III) chelates of these poly-DOTA branched polymers (P1-Gd, P2-Gd, P3-Gd, and P4-Gd) display excellent kinetic stability, which is significantly higher than those of linear Gd-DTPA and cyclic Gd-DOTA-butrol and slightly lower than that of cyclic Gd-DOTA. The T1 relaxivities of P1-Gd, P2-Gd, P3-Gd, and P4-Gd are 29.4, 38.7, 44.0, and 47.9 Gd mM-1 s-1, respectively, at 0.5 T, which are about 6-11 times higher than that of Gd-DOTA (4.4 Gd mM-1 s-1). P4-Gd was selected for in vivo magnetic resonance angiography (MRA) because of its high kinetic stability, T1 relaxivity, and good biosafety. The results showed excellent MRA effect, sensitive detection of vascular stenosis, and prolonged observation window as compared to Gd-DOTA. Overall, Gd(III) chelates of poly-DOTA branched polymers are good candidates of MRI probes, providing a unique design strategy in which Gd chelation can occur at both the interior and surface of the poly-DOTA branched polymers, resulting in excellent relaxivity enhancement. In vivo animal MRA studies of the probe provide possibilities in discovering small vascular pathologies.
Subject(s)
Organometallic Compounds , Polymers , Animals , Magnetic Resonance Angiography , Gadolinium , Magnetic Resonance Imaging/methods , Contrast Media , Chelating AgentsABSTRACT
Polymeric micelles have long been considered as promising nanocarrier for hydrophobic drugs and imaging probes, due to their nanoscale particle size, biocompatibility and ability to loading reasonable amount of cargoes. Herein, a facile method for dextran micelles preparation was developed and their performance as carriers of superparamagnetic iron oxide (SPIO) nanocrystals was evaluated. Amphiphilic dextran (Dex-g-OA) was synthesized via the Schiff base reactions between oxidized dextran and oleylamine, and self-assembled in situ into nano-size micelles in the reaction systems. The self-assembling behaviors of the amphiphilic dextran were identified using fluorescence resonance energy transfer technique by detection the energy transfer signal between the fluorophore pairs, Cy5 and Cy5.5. Hydrophobic SPIO nanoparticles (Fe3O4 NPs) were successfully loaded into the dextran micelles via the in situ self-assembly process, leading to a series of Fe3O4 NPs-loaded micelle nanocomposites (Fe3O4@Dex-g-OA) with good biocompatibility, superparamagnetism and strongly enhanced T 2 relaxivity. At the magnetic field of 0.5 T, the Fe3O4@Dex-g-OA nanocomposite with particle size of 116.2 ± 53.7 nm presented a higher T 2 relaxivity of 327.9 mM Fe - 1 ·s-1. The prepared magnetic nanocomposites hold the promise to be used as contrast agents in magnetic resonance imaging.
ABSTRACT
The development of an effective method for staging liver fibrosis has always been a hot topic of research in the field of liver fibrosis. In this paper, PEGylated ultrafine superparamagnetic iron oxide nanocrystals (SPIO@PEG) were developed for T 1-T 2 dual-modal contrast-enhanced magnetic resonance imaging (MRI) and combined with Matrix Laboratory (MATLAB)-based image fusion for staging liver fibrosis in the rat model. Firstly, SPIO@PEG was synthesized and characterized with physical and biological properties as a T 1-T 2 dual-mode MRI contrast agent. Secondly, in the subsequent MR imaging of liver fibrosis in rats in vivo, conventional T 1 and T 2-weighted imaging, and T 1 and T 2 mapping of the liver pre- and post-intravenous administration of SPIO@PEG were systematically collected and analyzed. Thirdly, by creative design, we fused the T 1 and T 2 mapping images by MATLAB and quantitively measured each rat's hepatic fibrosis positive pixel ratio (PPR). SPIO@PEG was proved to have an ultrafine core size (4.01 ± 0.16 nm), satisfactory biosafety and T 1-T 2 dual-mode contrast effects under a 3.0 T MR scanner (r 2/r 1 = 3.51). According to the image fusion results, the SPIO@PEG contrast-enhanced PPR shows significant differences among different stages of liver fibrosis (P < 0.05). The combination of T 1-T 2 dual-modal SPIO@PEG and MATLAB-based image fusion technology could be a promising method for diagnosing and staging liver fibrosis in the rat model. PPR could also be used as a non-invasive biomarker to diagnose and discriminate the stages of liver fibrosis.
ABSTRACT
Polymer micelles formed by self-assembly of amphiphilic polymers are widely used in drug delivery, gene delivery and biosensors, due to their special hydrophobic core/hydrophilic shell structure and nanoscale. However, the structural stability of polymer micelles can be affected strongly by environmental factors, such as temperature, pH, shear force in the blood and interaction with non-target cells, leading to degradations and drug leakage as drug carriers. Therefore, researches on the structural integrity and in vivo distribution of micelle-based carriers are very important for evaluating their therapeutic effect and clinical feasibility. At present, fluorescence resonance energy transfer (FRET) technology has been widely used in real-time monitoring of aggregation, dissociation and distribution of polymer micelles ( in vitro and in vivo). In this review, the polymer micelles, characteristics of FRET technology, structure and properties of the FRET-polymer micelles are briefly introduced. Then, methods and mechanism for combinations of several commonly used fluorescent probes into polymer micelles structures, and progresses on the stability and distribution studies of FRET-polymer micelles ( in vitro and in vivo) as drug carriers are reviewed, and current challenges of FRET technology and future directions are discussed.
Subject(s)
Drug Carriers , Micelles , Drug Carriers/chemistry , Polymers/chemistry , Fluorescence Resonance Energy Transfer , Polyethylene Glycols/chemistryABSTRACT
This study aims to explore the potential of polyaspartic acid grafted dopamine copolymer (PAsp- g-DA) chelated Fe 3+ for magnetic resonance imaging (MRI) visual photothermal therapy. Polyaspartic acid grafted copolymer of covalently grafted dopamine and polyethylene glycol (PAsp- g-DA/PEG) was obtained by the ammonolysis reaction of poly succinimide (PSI), and then chelated with Fe 3+ in aqueous solution. The relaxivity in vitro, magnetic resonance imaging enhancement in vivo and photothermal conversion effect at 808 nm were investigated. The results showed that polymeric iron coordination had good near-infrared absorption and photothermal conversion properties, good magnetic resonance enhancement effect, and good longitudinal relaxation efficiency under different magnetic field intensities. In summary, this study provides a new magnetic resonance visual photothermal therapeutic agent and a new research idea for the research in related fields.
Subject(s)
Nanoparticles , Polymers , Dopamine , Magnetic Resonance Imaging/methods , Peptides , Phototherapy , Photothermal TherapyABSTRACT
Currently, the most commonly used clinical magnetic resonance imaging (MRI) contrast agents, Gd(III) chelates, have been found to be associated with nephrogenic systemic fibrosis (NSF) in renally compromised patients. Toxicity concerns related to Gd(III)-based agents prompted intensive research toward the development of safe, efficient, and long-cycle non-Gd contrast agents. Herein, three amphiphilic polymeric manganese (Mn) ligands (mPEG1k-P(L-a-HMDI)-mPEG1k, mPEG2k-P(L-a-HMDI)-mPEG2k and mPEG4k-P(L-a-HMDI)-mPEG4k) were synthesized, and then end-capped respectively with different molecular weights of polyethylene glycol monomethyl ether (mPEG 1 kD, 2 kD and 4 kD) to obtain amphiphilic polymer Mn ligands. After being chelated with Mn(II), these amphiphilic polymer Mn complexes show significantly higher T1 relaxivity than the small molecule Mn complex (MnL) at 0.5 T, 1.5 T and 3.0 T magnetic fields, respectively. Then, mPEG2k-P(MnL-a-HMDI)-mPEG2k with relatively high T1 relaxivities (23.2, 14.4 and 9.7 mM-1s-1 at 0.5 T, 1.5 T and 3.0 T, respectively), low CMC (4.7 mg L-1), reasonable size (48 nm) and excellent stability among these three polymer Mn complexes was selected for in vivo MR imaging of vascular vessels. The results suggest that mPEG2k-P(MnL-a-HMDI)-mPEG2k has an excellent and relatively long time-window vascular enhancement effect even at a low dose of 0.05 mmol Mn kg-1 BW, and could play a role in the diagnosis of vascular diseases (0.1 mmol Mn kg-1 BW). Therefore, mPEG2k-P(MnL-a-HMDI)-mPEG2k may be considered as a potential blood pool contrast agent.
Subject(s)
Contrast Media , Manganese , Humans , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy , Polyethylene GlycolsABSTRACT
Liver-specific contrast agents (CAs) can improve the Magnetic resonance imaging (MRI) detection of focal and diffuse liver lesions by increasing the lesion-to-liver contrast. A novel Mn(II) complex, Mn-BnO-TyrEDTA, with a lipophilic group-modified ethylenediaminetetraacetic acid (EDTA) structure as a ligand to regulate its behavior in vivo, is superior to Gd-EOB-DTPA in terms of a liver-specific MRI contrast agent. An MRI study on mice demonstrated that Mn-BnO-TyrEDTA can be rapidly taken up by hepatocytes with a combination of hepatobiliary and renal clearance pathways. Bromosulfophthalein (BSP) inhibition imaging, biodistribution, and cellular uptake studies confirmed that the mechanism of hepatic targeting of Mn-BnO-TyrEDTA is the hepatic uptake of the amphiphilic anion contrast agent mediated by organic anion transporting polypeptides (OATPs) expressed by functional hepatocytes.
Subject(s)
Contrast Media/pharmacokinetics , Coordination Complexes/pharmacokinetics , Edetic Acid/pharmacokinetics , Hepatocytes/metabolism , Magnetic Resonance Imaging , Manganese/pharmacokinetics , Animals , Cell Line , Cell Survival/drug effects , Contrast Media/chemical synthesis , Contrast Media/chemistry , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Edetic Acid/chemistry , Hepatocytes/chemistry , Hepatocytes/drug effects , Humans , Hydrophobic and Hydrophilic Interactions , Manganese/chemistry , Mice , Molecular Structure , Rats , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
BACKGROUND: Early recurrence of oesophageal squamous cell carcinoma (SCC) is defined as recurrence after surgery within 1 year, and appears as local recurrence, distant recurrence, and lymph node positive and disseminated recurrence. Contrast-enhanced computed tomography (CECT) is recommended for diagnosis of primary tumor and initial staging of oesophageal SCC, but it cannot be used to predict early recurrence. It is reported that radiomics can help predict preoperative stages of oesophageal SCC, lymph node metastasis before operation, and 3-year overall survival of oesophageal SCC patients following chemoradiotherapy by extracting high-throughput quantitative features from CT images. This study aimed to develop models based on CT radiomics and clinical features of oesophageal SCC to predict early recurrence of locally advanced cancer. METHODS: We collected electronic medical records and image data of 197 patients with confirmed locally advanced oesophageal SCC. These patients were randomly allocated to 137 patients in the training cohort and 60 in the test cohort. 352 radiomics features were extracted by delineating region-of-interest (ROI) around the lesion on CECT images and clinical signature was generated by medical records. The radiomics model, clinical model, the combined model of radiomics and clinical features were developed by radiomics features and/or clinical characteristics. Predicting performance of the three models was assessed with area under receiver operating characteristic curve (AUC), accuracy and F-1 score. RESULTS: Eleven radiomics features and/or six clinical signatures were selected to build prediction models related to recurrence of locally advanced oesophageal SCC after trimodal therapy. The AUC of integration of radiomics and clinical models was better than that of radiomics or clinical model for the training cohort (0.821 versus 0.754 or 0.679, respectively) and for the validation cohort (0.809 versus 0.646 or 0.658, respectively). Integrated model of radiomics and clinical features showed good performance in predicting early recurrence of locally advanced oesophageal SCC for both the training and validation cohorts (accuracy = 0.730 and 0.733, and F-1score = 0.730 and 0.778, respectively). CONCLUSIONS: The integrated model of CECT radiomics and clinical features may be a potential imaging biomarker to predict early recurrence of locally advanced oesophageal SCC after trimodal therapy.
Subject(s)
Contrast Media/therapeutic use , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/radiotherapy , Radiometry/methods , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
BACKGROUND: Prediction of lymph node status in esophageal squamous cell carcinoma (ESCC) is critical for clinical decision making. In clinical practice, computed tomography (CT) has been frequently used to assist in the preoperative staging of ESCC. Texture analysis can provide more information to reflect potential biological heterogeneity based on CT. A nomogram for the preoperative diagnosis of lymph node metastasis in patients with resectable ESCC has been previously developed. However, to the best of our knowledge, no reports focus on developing CT radiomics features to discriminate ESCC patients with regional lymph node metastasis (RLNM) and non-regional lymph node metastasis (NRLNM). We, therefore, aimed to develop CT radiomics models to predict lymph node metastasis (LNM) in advanced ESCC and to discriminate ESCC between RLNM and NRLNM. METHODS: This study enrolled 334 patients with pathologically confirmed advanced ESCC, including 152 patients without LNM and 182 patients with LNM, and 103 patients with RLNM and 79 patients NRLNM. Radiomics features were extracted from CT data for each patient. The least absolute shrinkage and selection operator (LASSO) model and independent samples t-tests or Mann-Whitney U tests were exploited for dimension reduction and selection of radiomics features. Optimal radiomics features were chosen using multivariable logistic regression analysis. The discriminating performance was assessed by area under the receiver operating characteristic curve (AUC) and accuracy. RESULTS: The radiomics features were developed based on multivariable logistic regression and were significantly associated with LNM status in both the training and validation cohorts (P<0.001). The radiomics models could differentiate between patients with and without LNM (AUC =0.79 and 0.75, and accuracy =0.75 and 0.71 in the training and validation cohorts, respectively). In patients with LNM, the radiomics features could effectively differentiate between RLNM and NRLNM (AUC =0.98 and 0.95, and accuracy =0.94 and 0.83 in the training and validation cohorts, respectively). CONCLUSIONS: CT radiomics features could help predict the LNM status of advanced ESCC patients and effectively discriminate ESCC between RLNM and NRLNM.
ABSTRACT
OBJECTIVE: PEGylated superparamagnetic iron oxide (SPIO) is the most promising alternatives to gadolinium-based contrast agents (GBCAs) in MRI. This paper is to explore the imaging effects of PEGylated SPIO, which is influenced by particle sizes and surface polyethylene glycol (PEG) coating, using as MRI contrast agents at different magnetic field intensities. METHODS: Firstly, nine PEGylated monocrystalline SPIO nanoparticles with different nanocrystal sizes and different molecular weights PEG coating were prepared, and then physical and biological properties were analyzed. Finally, MRI imaging in vivo was performed to observe the imaging performance. RESULTS: Nine PEGylated monocrystalline SPIO nanoparticles have good relaxivities, serum stability, and biosecurity. At the same time, they show different imaging characteristics at different magnetic field intensities. Eight-nanometer SPIO@PEG5k is an effective T 2 contrast agent at 3.0 T (r 2/r 1 = 14.0), is an ideal T 1-T 2 dual-mode contrast agent at 1.5 T (r 2/r 1 = 6.52), and is also an effective T 1 contrast agent at 0.5 T (r 2/r 1 = 2.49), while 4-nm SPIO@PEG5k is a T 1-T 2 dual-mode contrast agent at 3.0 T (r 2/r 1 = 5.24), and is a useful T 1 contrast agent at 0.5 T (r 2/r 1 = 1.74) and 1.5 T (r 2/r 1 = 2.85). MRI studies in vivo at 3.0 T further confirm that 4-nm SPIO@PEG5k displays excellent T 1-T 2 dual-mode contrast enhancement, whereas 8-nm SPIO@PEG5k only displays T 2 contrast enhancement. CONCLUSION: PEGylated SPIOs with different nanocrystal sizes and PEG coating can be used as T 1, T 2, or T 1-T 2 dual-mode contrast agents to meet the clinical demands of MRI at specific magnetic fields.
Subject(s)
Contrast Media/chemistry , Magnetic Iron Oxide Nanoparticles/chemistry , Magnetic Resonance Imaging , Nanocomposites/chemistry , Polyethylene Glycols/chemistry , Animals , Magnetic Fields , Magnetic Iron Oxide Nanoparticles/ultrastructure , Male , Mice , Nanocomposites/ultrastructure , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Particle Size , RAW 264.7 Cells , Rats, Sprague-Dawley , Serum/metabolismABSTRACT
We have designed and developed an effective drug delivery system using biocompatible polymer of poly (ethylene glycol)-polyaspartic acid (mPEG-PAsp) for co-loading the chemotherapy drugs paclitaxel (PTX) and cisplatin (CP) in one nano-vehicle. This study aimed to improve the anti-cancer efficacy of combinations of chemotherapy drugs and reduce their side effects. mPEG-PAsp-(PTX/Pt) nano-micelles disperse well in aqueous solution and have a narrow size distribution (37.8 ± 3.2 nm) in dynamic light scattering (DLS). Drug release profiles found that CP released at pH 5.5 was significantly faster than that at pH 7.4. MPEG-PAsp-(PTX/Pt) nano-micelles displayed a significantly higher tumor inhibitory effect than mPEG-PAsp-PTX nano-micelles when the polymer concentrations reached 50 µg/mL. Our data indicated that polymer micelles of mPEG-PAsp loaded with the combined drug exert synergistic anti-tumor efficacy on SKOV3 ovarian cells via different action mechanisms. Results from our studies suggested that mPEG-PAsp-(PTX/Pt) nano-micelles are promising alternatives for carrying and improving the delivery of therapeutic drugs with different water solubilities.