Texture analysis on gadoxetic acid enhanced-MRI for predicting Ki-67 status in hepatocellular carcinoma: A prospective study

Objective: To investigate the value of whole-lesion texture analysis on preoperative gadoxetic acid enhanced magnetic resonance imaging(MRI) for predicting tumor Ki-67 status after curative resection in patients with hepatocellular carcinoma(HCC).Methods: This study consisted of 89 consecutive patients with surgically confirmed HCC. Texture features were extracted from multiparametric MRI based on whole-lesion regions of interest. The Ki-67 status was immunohistochemical determined and classified into low Ki-67(labeling index ≤15%) and high Ki-67(labeling index >15%) groups. Least absolute shrinkage and selection operator(LASSO) and multivariate logistic regression were applied for generating the texture signature, clinical nomogram and combined nomogram. The discrimination power, calibration and clinical usefulness of the three models were evaluated accordingly. Recurrence-free survival(RFS) rates after curative hepatectomy were also compared between groups.Results: A total of 13 texture features were selected to construct a texture signature for predicting Ki-67 status in HCC patients(C-index: 0.878, 95% confidence interval: 0.791-0.937). After incorporating texture signature to the clinical nomogram which included significant clinical variates(AFP, BCLC-stage, capsule integrity, tumor margin,enhancing capsule), the combined nomogram showed higher discrimination ability(C-index: 0.936 vs. 0.795,P<0.001), good calibration(P>0.05 in Hosmer-Lemeshow test) and higher clinical usefulness by decision curve analysis. RFS rate was significantly lower in the high Ki-67 group compared with the low Ki-67 group after curative surgery(63.27% vs. 85.00%, P<0.05).Conclusions: Texture analysis on gadoxetic acid enhanced MRI can serve as a noninvasive approach to preoperatively predict Ki-67 status of HCC after curative resection. The combination of texture signature and clinical factors demonstrated the potential to further improve the prediction performance.

Multifunctional dextran micelles as drug delivery carriers and magnetic resonance imaging probes

Multifunctional nanoparticles combining diagnostic and therapeutic agents into a single platform make cancer theranostics possible and have attracted wide interests in the field. In this study, a multifunctional nanocomposite based on dextran and superparamagnetic iron oxide nanoparticles(SPIO) was prepared for drug delivery and magnetic resonance imaging(MRI). Amphiphilic dextran was synthesized by grafting stearyl acid onto the carbohydrate backbone, and micelle was formed by the resulted amphiphilic dextran with low critical micelle concentration at 1.8 mg L-1. Doxorubicin(DOX) and a cluster of the manganese-doped iron oxide nanoparticles(Mn-SPIO)nanocrystals were then coencapsulated successfully inside the core of dextran micelles, resulting in nanocomposites with diameter at about 100 nm. Cell culture experiments demonstrated the potential of these Mn-SPIO/DOX nanocomposites as an effective multifunctional nanoplatform for the delivery of anticancer drug DOX with a loading content(DLC) of 16 %. Confocal laser scanning microscopyreveals that the Mn-SPIO/DOX had excellent internalization ability against MCF-7/Adr cells after 2-h labeling compared with free DOXáHCl. Under a 3.0-T MRI scanner, Mn-SPIO/DOX nanocomposite-labeled cells in gelatin phantom show much darker images than the control. Their transverse relaxation(T2) rate is also significantly higher than that of the control cells(33.9 versus 2.3 s-1). Our result offers an effective strategy to treat MCF-7/Adr at optimized low dosages with imaging capability.

Recent advances of deep learning in psychiatric disorders

Deep learning(DL)is a recently proposed subset of machine learning methods that has gained extensive attention in the academic world,breaking benchmark records in areas such as visual recognition and natural language processing.Different fromconventional machine learning algorithm,DL is able to learn useful representations and features directly from raw data through hierarchical nonlinear transformations.Because of its ability to detect abstract and complex patterns,DL has been used in neuroimaging studies of psychiatric disorders,which are characterized by subtle and diffuse alterations.Here,we provide a brief review of recent advances and associated challenges in neuroimaging studies of DL applied to psychiatric disorders.The results of these studies indicate that DL could be a powerful tool in assisting the diagnosis of psychiatric diseases.We conclude our review by clarifying the main promises and challenges of DL application in psychiatric disorders,and possible directions for future research.

The effect of neighbor distance of magnetic nanoparticle clusters on magnetic resonance relaxation properties

Superparamagnetic iron oxide(SPIO) nanoparticle clusters are one unique form which can enhance magnetic relaxivity and improve the magnetic resonance imaging contrast at the same iron concentration, comparing to single SPIO nanoparticles. Controlling of cluster size and other structural parameters have drawn great interests in this field to further improve their magnetic properties. In this study, we investigated how the interparticle distance(also known as neighbor distance) of SPIO nanocrystals within clusters affect their magnetic relaxation behaviors.To adjust the neighbor distance, different amount of cholesterol(CHO) was chosen as model spacers embedded into SPIO nanocluster systems with the help of amphiphilic diblock copolymer poly(ethylene glyco)-polyester. Smallangle X-ray scattering was applied to quantify the neighbor distance of SPIO clusters. The results demonstrated that the averaged SPIO nanocrystal neighbor distance of nanoclusters increased with higher amount of added CHO.Moreover, these SPIO nanocrystal clusters had the prominent magnetic relaxation properties. Simultaneously, controlling of SPIO nanocrystal neighbor distance can regulate the saturation magnetization(Ms) and magnetic resonance(MR) T2 relaxation of the aggregation, and ultimately obtain better MR contrast effects with decreased neighbor distance.

Tetraphenylethylene-conjugated polycation covered iron oxide nanoparticles for magnetic resonance/optical dual-mode imaging

Magnetic resonance(MR)/optical dual-mode imaging with high sensitivity and high tissue resolution have attracted many attentions in biomedical applications.To avert aggregation-caused quenching of conventional fluorescence chromophores,an aggregation-induced emission molecule tetraphenylethylene(TPE)-conjugated amphiphilic polyethylenimine(PEI)covered superparamagnetic iron oxide(Alkyl-PEI-LAC-TPE/SPIO nanocomposites)was prepared as an MR/optical dual-mode probe.Alkyl-PEI-LAC-TPE/SPIO nanocomposites exhibited good fluorescence property and presented higher T2 relaxivity(352 Fe mM1s1)than a commercial contrast agent Feridex(120 Fe mM1s1)at 1.5 T.The alkylation degree of Alkyl-PEI-LAC-TPE effects the restriction of intramolecular rotation process of TPE.Reducing alkane chain grafting ratio aggravated the stack of TPE,increasing the fluorescence lifetime of Alkyl-PEI-LAC-TPE/SPIO nanocomposites.Alkyl-PEI-LAC-TPE/SPIO nanocomposites can effectively labelled HeLa cells and resulted in high fluorescence intensity and excellent MR imaging sensitivity.As an MR/optical imaging probe,Alkyl-PEI-LAC-TPE/SPIO nanocomposites may be used in biomedical imaging for certain applications.

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T_(1)-T_(2) dual-mode magnetic resonance imaging probes

The T_(1)-T_(2) dual-mode probes for magnetic resonance imaging(MRI)can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time,making MRI a more flexible imaging modality for complicated applications.In this work,three Gadolinium-diethylene-triaminepentaaceticacid(Gd-DTPA)complex conjugated superparamagnetic iron oxide(SPIO)nanoparticles with different Gd/Fe molar ratio(0.94,1.28 and 1.67)were prepared as T_(1)-T_(2) dual-mode MRI probes,named as SPIO@PEG-GdDTPA0.94,SPIO@PEGGdDTPA1.28 and SPIO@PEG-GdDTPA1.67,respectively.All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3þchelate stability.SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67.SPIO@PEG-GdDTPA0.94 nanocomposites with r1(8.4mM^(-1)s^(-1)),r2(83.2mM^(-1)s^(-1))and relatively ideal r2/r1 ratio(9.9)were selected for T_(1)-T_(2) dual-mode MRI of blood vessels and liver tissue in vivo.Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner.Importantly,one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h.Overall,the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians,e.g.saving time,lowering side effects and collecting data of different organs sequentially.

Kinetically inert manganese(II)-based hybrid micellar complexes for magnetic resonance imaging of lymph node metastasis

The localization and differential diagnosis of the sentinel lymph nodes(SLNs)are particularly important for tumor staging,surgical planning and prognosis.In this work,kinetically inert manganese(II)-based hybrid micellar complexes(MnCs)for magnetic resonance imaging(MRI)were developed using an amphiphilic manganese-based chelate(C18-PhDTA-Mn)with reliable kinetic stability and self-assembled with a series of amphiphilic PEG-C18 polymers of different molecular weights(C18En,n=10,20,50).Among them,the probes composed by 1:10 mass ratio of manganese chelate/C18En had slightly different hydrodynamic particle sizes with similar surface charges as well as considerable relaxivities(∼13 mM^(−1)s^(−1)at 1.5 T).In vivo lymph node imaging in mice revealed that the MnC MnC-20 formed by C18E20 with C18-PhDTA-Mn at a hydrodynamic particle size of 5.5 nm had significant signal intensity brightening effect and shortened T1 relaxation time.At an imaging probe dosage of 125μg Mn/kg,lymph nodes still had significant signal enhancement in 2 h,while there is no obvious signal intensity alteration in non-lymphoid regions.In 4T1 tumor metastatic mice model,SLNs showed less signal enhancement and smaller T1 relaxation time variation at 30 min post-injection,when compared with normal lymph nodes.This was favorable to differentiate normal lymph nodes from SLN under a 3.0-T clinical MRI scanner.In conclusion,the strategy of developing manganese-based MR nanoprobes was useful in lymph node imaging.

Ultra-small superparamagnetic iron oxide nanoparticles for intra-articular targeting of cartilage in early osteoarthritis

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.