Tumor-targeted glycogen nanoparticles loaded with hemin and glucose oxidase to promote tumor synergistic therapy.

Strategies which are used to address the low levels of intracellular hydrogen peroxide and the development of biocompatible catalysts still need to be fulfilled in tumor chemodynamic therapy. Therefore, a novel tumor-targeted glycogen-based nanoparticle system (GN/He/GOx/HA) was developed to co-deliver hemin (He) and GOx, which can self-supply glucose formed upon degradation of glycogen by α-glycosidase in the lysosome environment, in order to achieve synergistic antitumor therapy. Hyaluronic acid (HA) was selected as the outer shell to protect the activity of GOx, and to increase the uptake by tumor cells via CD44 receptor-mediated endocytosis. GN/He/GOx/HA NPs had a good stability in the blood circulation, but fast release of the therapeutic cargos upon intracellular uptake. Hemin had a cascade catalytic reaction with GOx. Furthermore, GN/He/GOx/HA NPs had the strongest cytotoxicity in Hela cells in a glucose concentration dependent manner. The NPs could efficiently produce reactive oxygen species in tumor cells, resulting in a decrease in the mitochondrial membrane potential and apoptosis of tumor cells. The in vivo results showed that the drug-loaded nanoparticles had good safety, biocompatibility, and efficacious antitumor effect. Therefore, the glycogen-based nanoparticle delivery system provides potential application for self-enhancing CDT, which can be used for effective antitumor therapy.

Improvement of olfactory fMRI activation and hemodynamic response function curve with respiration correction.

BACKGROUND: Odor perception is highly dependent on respiration, however, the asynchronization between inspiration and odor delivery results in a decreased activation and hemodynamic response function (HRF) curve in olfactory functional MRI (fMRI). This study aimed to investigate the effect of a data post-processing method to minimize the asynchronization and consequently improve the olfactory activation and HRF curve and compare it between different TRs (3 s and 1 s). NEW METHOD: A new data post-processing method of respiration correction based on olfactory perception was investigated. COMPARISON WITH EXISTING METHODS: The odor stimuli of olfactory fMRI were mostly based on odor deliveries. But for the reason of respiration, the time of olfactory perception might be a little different. The actual onset time and duration of odor stimuli were modified based on the respiration data. RESULTS: For 3 s TR data, an increased number of activated voxels and higher HRF curves response height were obtained with the respiration correction method in the primary olfactory cortex (POC) (P = 0.034 and 0.009) and insula (P = 0.024 and 0.001), compared with the uncorrected method. But the activated voxels and response height of the anterior cingulate cortex (ACC) did not differ between uncorrected and respiration correction methods (P = 0.102 and 0.200). The time to peak of the HRF curve was shorter with the respiration correction method in all ROIs (all P < 0.05), compared with the uncorrected method. Whereas there were no significant differences between the uncorrected and corrected results for 1 s TR data. CONCLUSIONS: The post-processing method of respiration correction could effectively minimize the asynchronization between respirations and odor deliveries, and improve the activations and HRF curves for a routine 3 s TR olfactory fMRI data.

Tissue perfusion of the kurtosis/diffusion mismatch differs from the central core and peripheral regions in acute cerebral infarction patients.

BACKGROUND: Despite its wide adoption in stroke imaging, the diffusion-weighted imaging (DWI) lesion is heterogeneous. The emerging diffusion kurtosis imaging (DKI) has been postulated to resolve the graded DWI lesion. PURPOSE: To determine the perfusion characteristics of the central infarction core, kurtosis/diffusion mismatch, and peripheral regions. MATERIAL AND METHODS: Patients with acute ischemic stroke underwent DWI, DKI, and perfusion-weighted imaging (PWI) scans. The patients were divided into mean kurtosis (MK)/mean diffusivity (MD) match and mismatch groups. Perfusion parameters were measured in the MK/MD lesion and peripheral areas in the MK/MD match group. We also analyzed perfusion status in the MK/MD lesion mismatch area for the mismatch group. RESULTS: A total of 40 eligible patients (24 MK/MD match and 16 MK/MD mismatch) were enrolled in the final data analysis. The MTT and TTP progressively decreased, while the cerebral blood flow (CBF) and cerebral blood volume (CBV) increased from the central to peripheral areas. In addition, CBF in the MK/MD mismatch region was significantly higher than that in the central region (P < 0.05), but similar to the peripheral region. Furthermore, CBV in the MK/MD mismatch region did not differ significantly from that of the central region, but both were significantly lower than that of the peripheral area (P < 0.05). CONCLUSION: The MK/MD mismatch region had blood flow similar to the peripheral region but with a reduced blood volume, indicating that it was less ischemic from the infarction core, albeit insufficient collateral circulation.

Dual-energy CT iodine map in predicting the efficacy of neoadjuvant chemotherapy for hypopharyngeal carcinoma: a preliminary study.

Neoadjuvant chemotherapy has become one of the important means for advanced hypopharyngeal carcinoma. So far, there is no effective index to predict the curative effect. To investigate the value of iodine map of dual-energy computed tomography (CT) in predicting the efficacy of neoadjuvant chemotherapy for hypopharyngeal carcinoma. A total of 54 hypopharyngeal carcinomapatients who underwent two courses of TPF neoadjuvant chemotherapy were recruited in this study. Three cases had a complete response (CR), thirty-six cases had a partial response (PR), eleven cases had stable disease (SD), and four cases had a progressive disease (PD) after the chemotherapy. All patients underwent a dual-source CT scan before chemotherapy and rescanned after chemotherapy. The normalized iodine-related attenuation (NIRA) of the mean of maximum slice and most enhanced region of lesion at arterial and parenchymal phase were measured: NIRAmean-A, NIRAmax-A, NIRAmean-P, and NIRAmax-P, respectively. Correlation analysis was conducted between different metrics of NIRA and the diameter change rate of lesions, and the curative effect was evaluated based on the receiver operating characteristic (ROC) curve. There were a significant correlation between NIRAmean-A, NIRAmax-A, NIRAmean-P, NIRAmax-P and the change rate of lesion's maximum diameter (ΔD%) (all P < 0.01). The NIRAmax-A, NIRAmean-P, NIRAmax-P had significant differences between CR, PR, SD, PD groups, but NIRAmean-A did not reach a significant difference. All NIRAmean-A, NIRAmax-A, NIRAmean-P, NIRAmax-P had significant differences between effective (CR + PR) and ineffective (SD + PD) groups. The ROC analysis revealed that NIRAmean-P had the largest AUC and prediction efficacy (AUC = 0.809). Dual-energy CT iodine map could predict the efficacy of neoadjuvant chemotherapy and provides imaging evidence to assist in treatment decisions for hypopharyngeal carcinoma patients.

CT-based radiomics signature analysis for evaluation of response to induction chemotherapy and progression-free survival in locally advanced hypopharyngeal carcinoma.

OBJECTIVES: To establish and validate a CT radiomics model for prediction of induction chemotherapy (IC) response and progression-free survival (PFS) among patients with locally advanced hypopharyngeal carcinoma (LAHC). METHODS: One hundred twelve patients with LAHC (78 in training cohort and 34 in validation cohort) who underwent contrast-enhanced CT (CECT) scans prior to IC were enrolled. Least absolute shrinkage and selection operator (LASSO) was used to select the crucial radiomic features in the training cohort. Radiomics signature and clinical data were used to build a radiomics nomogram to predict individual response to IC. Kaplan-Meier analysis and log-rank test were used to evaluate ability of radiomics signature in progression-free survival risk stratification. RESULTS: The radiomics signature consisted of 6 selected features from the arterial and venous phases of CECT images and demonstrated good performance in predicting the IC response in both two cohorts. The radiomics nomogram showed good discriminative performance, and the C-index of nomogram was 0.899 (95% confidence interval (CI), 0.831-0.967) and 0.775 (95% CI, 0.591-0.959) in the training and validation cohorts, respectively. Survival analysis indicated that low-risk and high-risk groups defined by the value of radiomics signature had significant difference in PFS (3-year PFS 66.4% vs 29.7%, p < 0.001). CONCLUSIONS: Multiparametric CT-based radiomics model could be useful for predicting treatment response and PFS in patients with LAHC who underwent IC. KEY POINTS: • CT radiomics can predict IC response and progression-free survival in hypopharyngeal carcinoma. • We combined significant radiomics signature with clinical predictors to establish a nomogram to predict individual response to IC. • Radiomics signature could divide patients into the high-risk and low-risk groups based on the PFS.

Computed tomography-based radiomics signature as a pretreatment predictor of progression-free survival in locally advanced hypopharyngeal carcinoma with a different response to induction chemotherapy.

PURPOSE: To establish and validate a radiomics signature for stratifying the risk of progression-free survival (PFS) in patients with locally advanced hypopharyngeal carcinoma (LAHC) undergoing induction chemotherapy (IC). METHODS: We extracted radiomics features from baseline contrast-enhanced computed tomography (CECT) images. We enrolled 112 LAHC patients (78 in the training cohort and 34 in the validation cohort). We used cox regression model and random survival forests variable hunting (RSFVH) algorithm for feature selection and radiomics signature building. The radiomics signature was established in the training cohort and tested in the validation cohort. We used the Kaplan-Meier analysis and log-rank test to evaluate the ability of radiomics signature in PFS risk stratification among patients with different IC responses and constructed a radiomics nomogram to predict individual PFS risk. RESULTS: The radiomics signature performed well in stratifying patients into highrisk and low-risk groups of progression in both the training and validation cohorts. The radiomics nomogram showed good discriminative ability for predicting PFS. Survival outcome analysis of subsets indicated that the radiomics signature performed well in stratifying the risk of PFS in patients with LAHC with different IC responses. CONCLUSIONS: The radiomics signature was a pretreatment predictor for PFS in patients with LAHC who exhibited different responses to IC.

Stimuli-responsive, dual-function prodrug encapsulated in hyaluronic acid micelles to overcome doxorubicin resistance.

Multidrug resistance (MDR) is the main challenge faced by cancer chemotherapy. Drug-conjugate offers a promising strategy for breast cancer therapy. In this regard, we developed a DNVM multifunctional drug delivery system by crosslinking doxorubicin (DOX) and vitamin E succinate (VES) with a pH-sensitive hydrazone bond and then encapsulated the DOX-NN-VES prodrug into pH-sensitive hyaluronic acid-2-(octadecyloxy)-1,3-dioxan-5-amine (HOD) micelles. DOX resistant MCF-7/ADR cell were adopted as a model to study the capability and mechanism of MDR reversal. DNVM exhibited much higher cytotoxicity and cell uptake efficiency compared with that of acid-insensitive DOX-VES loaded HOD micelles (DVSM) and DOX loaded HOD micelles (DOXM), indicating the better capacity of DNVM for the reversal of MDR. Moreover, DNVM prevented drug efflux more effectively, inhibited the expression of P-gp, induced excessive production of reactive oxygen species and affected the expression of apoptosis-related proteins. In vivo experiments showed that DNVM significantly inhibited the tumor growth with no obvious changes in the body weight of MCF-7/ADR cells-bearing nude mice. The results suggested that the "double gain" DNVM can synergistically enhance the efficacy of chemotherapeutics for DOX resistant tumor cells and has the potential to overcome tumor MDR. STATEMENT OF SIGNIFICANCE: A dual-functional pH-sensitive doxorubicin - vitamin E succinate prodrug was developed and loaded into tumor microenvironment-sensitive hyaluronic acid-2-(octadecyloxy)-1,3-dioxan-5-amine micelle system (DNVM) for sequencing stimuli-release and overcoming doxorubicin resistance. The "double gain" DNVM can synergistically enhance the efficacy of chemotherapeutics for doxorubicin resistant tumor cells and has the potential to overcome tumor multiple drug resistance.

Occult primary white matter impairment in Leber hereditary optic neuropathy.

BACKGROUND AND PURPOSE: Leber hereditary optic neuropathy (LHON) is a disease maternally inherited from mitochondria that predominantly impairs the retinal ganglion cells and their axons. To identify whether occult brain white matter (WM) impairment is involved, a voxel-based analysis (VBA) of diffusion metrics was carried out in LHON patients with normal-appearing brain parenchyma. METHODS: Fifty-four symptomatic LHON patients (including 22 acute LHON with vision loss for ≤12 months, and 32 chronic LHON) without any visible brain lesions and 36 healthy controls (HCs) were enrolled in this study. VBA was applied to quantify the WM microstructural changes of LHON patients. Finally, the associations of the severity of WM impairment with disease duration and ophthalmologic deficits were assessed. RESULTS: Compared with the HCs, the average retinal nerve fiber layer (RNFL) thickness was significantly reduced in patients with chronic LHON, whereas it was increased in patients with acute LHON (p < 0.05, corrected). VBA identified significantly decreased fractional anisotropy widely in WM in both the acute and chronic LHON patients, including the left anterior thalamic radiation and superior longitudinal fasciculus, and bilateral corticospinal tract, dentate nuclei, inferior longitudinal fasciculus, forceps major, and optic radiation (OR; p < 0.05, corrected). The integrity of most WM structures (except for the OR) was correlated with neither disease duration nor RNFL thickness (p > 0.05, corrected). CONCLUSIONS: Occult primary impairment of widespread brain WM is present in LHON patients. The coexisting primary and secondary WM impairment may jointly contribute to the pathological process of LHON.

Overcoming multidrug resistance by intracellular drug release and inhibiting p-glycoprotein efflux in breast cancer.

Doxorubicin (DOX) is limited to use in clinical practice because of poor targeting, serious side effects and multidrug resistance (MDR). Vitamin E and its derivatives are currently considered as hydrophobic material that can reverse tumor MDR by suppressing the action of p-glycoprotein (p-gp). Therefore, reduction-sensitive amphiphilic heparosan polysaccharide-cystamine-vitamin E succinate (KSV) copolymers were designed to reverse breast cancer MDR cells. The spherical micelles (DOX/KSV) micelles which had suitable particle size presented redox-sensitive release character. Simultaneously, DOX-loaded reduction insensitive heparosan-adipic dihydrazide-vitamin E succinate (KV) micellar system was designed as a control. DOX/KSV and DOX/KV micelles had the higher capability to overcome tumor MDR than that free DOX. However, DOX/KSV had the highest amount of cellular uptake which might be caused by the synergistic intracellular drug release and inhibition of p-gp expression. The mechanism experiments revealed that DOX/KSV could be fast disassembled to release DOX after internalization into tumor cells. Moreover, DOX/KSV produced more ROS than free DOX and DOX/KV resulting in enhanced anticancer effect. In vivo tumor-bearing mice study suggested that DOX/KSV micelles could efficiently enhance antitumor effect by overcoming tumor MDR and reduce toxicity of DOX. The DOX/KSV micelles could synergistically increase the therapeutic effect of chemotherapeutic drug on tumor MDR cells.

Improved Activation and Hemodynamic Response Function of Olfactory fMRI Using Simultaneous Multislice with Reduced TR Acquisition.

OBJECTIVES: The respiration could decrease the time synchronization between odor stimulation and data acquisition, consequently deteriorating the functional activation and hemodynamic response function (HRF) in olfactory functional magnetic resonance imaging (fMRI) with a conventional repetition time (TR). In this study, we aimed to investigate whether simultaneous multislice (SMS) technology with reduced TR could improve the blood oxygen level-dependent (BOLD) activation and optimize HRF modeling in olfactory fMRI. METHODS: Sixteen young healthy subjects with normal olfaction underwent olfactory fMRI on a 3T MRI scanner using a 64 channel head coil. FMRI data were acquired using SMS acceleration at three different TRs: 3000 ms, 1000 ms, and 500 ms. Both metrics of BOLD activation (activated voxels, mean, and maximum t-scores) and the HRF modeling (response height and time to peak) were calculated in the bilateral amygdalae, hippocampi, and insulae. RESULTS: The 500 ms and 1000 ms TRs both significantly improved the number of activated voxels, mean, and maximum t-score in the amygdalae and insulae, compared with a 3000 ms TR (all P < 0.05). But the increase of these metrics in the hippocampi did not reach a statistical significance (all P > 0.05). No significant difference in any BOLD activation metrics between TR 500 ms and 1000 ms was observed in all regions of interest (ROIs) (all P > 0.05). The HRF curves showed that higher response height and shorter time to peak in all ROIs were obtained at 500 ms and 1000 ms TRs compared to 3000 ms TR. TR 500 ms had a more significant effect on response height than TR 1000 ms in the amygdalae (P = 0.017), and there was no significant difference in time to peak between TR 500 ms and 1000 ms in all ROIs (all P > 0.05). CONCLUSIONS: The fast image acquisition technique of SMS with reduced TR could significantly improve the functional activation and HRF curve in olfactory fMRI.

Redox-responsive biocompatible nanocarriers based on novel heparosan polysaccharides for intracellular anticancer drug delivery.

Heparosan is a natural precursor of heparin biosynthesis in mammals. It is stable in blood circulation but can be degraded in lysosomes, showing good biocompatibility and long circulation features. So heparosan can be designed as anticancer drug carriers to increase tumor selectivity and improve the therapeutic effect. A novel redox-sensitive heparosan-cystamine-vitamin E succinate (KSV) micelle system was constructed for intracellular delivery of doxorubicin (DOX). Simultaneously, the redox-insensitive heparosan-adipic acid dihydrazide-vitamin E succinate copolymer (KV) was synthesized as control. DOX-loaded micelles (DOX/KSV) with an average particle size of 90-120 nm had good serum stability and redox-triggered depolymerization. In vitro drug release test showed that DOX/KSV micelles presented obvious redox-triggered release behavior compared with DOX/KV. Cytotoxicity and cell uptake were investigated using MGC80-3 tumor cells and COS7 fibroblast-like cells. The cell survival rate of blank micelles was more than 90%, and the cytotoxicity of DOX/KSV in MGC80-3 cells was higher than in COS7 cells, indicating that the carrier has better biocompatibility and less toxicity side effect. The cytotoxicity of DOX/KSV against MGC80-3 cells was significantly greater than that of free DOX and DOX/KV. Furthermore, compared with DOX/KV in MGC80-3 cells, DOX/KSV micelles uptook more anticancer drugs and then released DOX faster into the cell nucleus. The micelles were endocytosed by multiple pathways, but clathrin-mediated endocytosis was the main pathway. Therefore, heparosan polysaccharide could be a potential option as anticancer carrier for enhancing efficacy and mitigating toxicity.

Elucidation of cellular uptake and intracellular trafficking of heparosan polysaccharide-based micelles in various cancer cells.

Heparosan polysaccharide, known as a heparin precursor, can be used in drug delivery systems due to its good biocompatibility and anti-cancer effect. But few studies on the cellular uptake mechanism of heparosan polysaccharide-based nanocarrier have been investigated. Therefore, the intracellular trafficking and the uptake mechanism of heparosan-based micelles by different tumor cells were investigated in this study. Heparosan-cholesterol amphipathic conjugates (KC) were constructed and doxorubicin (DOX) was loaded to prepare DOX/KC micelles. Different cancer cells were selected to find out the influence on DOX/KC uptake. There was an obvious difference in cytotoxicity and cellular uptake of DOX/KC in various cancer cells. Interestingly, DOX/KC micelles exhibited the strongest cytotoxicity against MGC80-3 cells and displayed highly cellular uptake by B16 cells. The results of the uptake mechanism showed that the internalization of DOX/KC micelles into MGC80-3 cells and A549 cells was mainly through clathrin-mediated endocytosis and macropinocytosis, while micropinocytosis, clathrin-mediated endocytosis and clathrin/caveolae -independent multi-pathways all contributed to the uptake of micelles in B16 cells. Furthermore, after being internalized by MGC80-3 cells, DOX/KC could escape from the lysosome and simultaneously be transported into the nucleus and mitochondria resulting in the greatest cytotoxicity. These results indicate that heparosan-based drug delivery systems may have different uptake and subcellular distribution behavior in tumor cells, and they will achieve the maximum efficacy only in specific kind of cancers.

Brain white matter changes in asymptomatic carriers of Leber's hereditary optic neuropathy.

OBJECTIVE: Subclinical abnormalities, including microangiopathy, swelling of nerve fibers, visual field abnormalities and visual functional impairments had been reported in Leber's hereditary optic neuropathy (LHON) carriers. The purpose of this study was to investigate microstructural changes of brain white matter in asymptomatic LHON carriers using DTI and tract-based spatial statistics (TBSS). METHODS: DTI and neuro-ophthalmologic measurements were acquired in 14 LHON carriers and 15 gender- and age-matched healthy controls, and diffusion metrics, including fractional anisotropy (FA), axial (AD), radial diffusion (RD) and mean diffusion (MD) were calculated. Intergroup differences in diffusion metrics were compared regressing out potential nuisance covariates of age and gender. A correlation analysis was performed to test associations between abnormal neuro-ophthalmologic measures and diffusion metrics while controlling the effects of age and gender. RESULTS: Compared to healthy controls, LHON carriers showed a weak increase of thickness of the retinal nerve fiber layer (RNFL) of the right inferior quadrant (F = 5.22, p = 0.032, before multiple comparison correction). LHON carriers exhibited widespread decreased FA value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, major and minor forceps, bilateral inferior fronto-occipital fasciculi and left superior longitudinal fasciculus), increased RD value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, major and minor forceps, bilateral inferior fronto-occipital fasciculi, bilateral inferior longitudinal fasciculi, bilateral superior longitudinal fasciculi and bilateral uncinate fasciculi) and increased MD value (bilateral anterior thalamic radiations, bilateral corticospinal tracts, minor forceps, bilateral inferior fronto-occipital fasciculi, bilateral inferior longitudinal fasciculi, left superior longitudinal fasciculus and bilateral uncinate fasciculi). Moreover, these changed diffusion metrics were not correlated with age, gender, LHON mutations and retinal measures in LHON carriers. CONCLUSION: Our results show microstructural alterations in brain white matter in asymptomatic LHON carriers, indicating that LHON-related genetic mutations themselves might result in occult white matter alterations in the brain.

Designing heparan sulfate-based biocompatible polymers and their application for intracellular stimuli-sensitive drug delivery.

Heparan sulfate (HS) is a kind of natural polysaccharides with good biocompatibility. And as drug carriers, it has some advantages compared to heparin. However, the preparation of HS is cumbersome and difficult, which limits its application in drug delivery. Here, we use modern separation technique combined with chromatography to establish a new preparation method of HS. The molecular weight and degree of dispersion of HS were (1.03 × 104 ±â€¯107) kDa and 1.106, respectively. HS also showed low anticoagulation activity in comparison with heparin. Subsequently, novel redox-sensitive heparan sulfate-cystamine-vitamin E succinate (HS-SS-VES, HSV) micelles were designed to increase tumor selectivity and improve the therapeutic effect of doxorubicin (DOX). DOX-loaded HSV micelles (DOX/HSV) with spherical morphology had average particle size of 90-120 nm and good redox-triggered release behavior. The cell viabilities of blank micelles were >90% in both human breast cancer (MCF7) cells and African green monkey SV40-transformed kidney fibroblast (COS7) cells. However, the cytotoxicity of DOX/HSV in MCF7 cells was higher than that of COS7 cells. Flow cytometry analyses and confocal laser scanning microscopy observation indicated that DOX/HSV micelles were internalized by endocytosis, and then the drug was released quickly and entered the nuclei of tumor cells. The results demonstrate that high-purity HS can be prepared and has the potential to be further used for drug delivery in antitumor applications.

Visual deprivation selectively reshapes the intrinsic functional architecture of the anterior insula subregions.

The anterior insula (AI) is the core hub of salience network that serves to identify the most relevant stimuli among vast sensory inputs and forward them to higher cognitive regions to guide behaviour. As blind subjects were usually reported with changed perceptive abilities for salient non-visual stimuli, we hypothesized that the resting-state functional network of the AI is selectively reorganized after visual deprivation. The resting-state functional connectivity (FC) of the bilateral dorsal and ventral AI was calculated for twenty congenitally blind (CB), 27 early blind (EB), 44 late blind (LB) individuals and 50 sighted controls (SCs). The FCs of the dorsal AI were strengthened with the dorsal visual stream, while weakened with the ventral visual stream in the blind than the SCs; in contrast, the FCs of the ventral AI of the blind was strengthened with the ventral visual stream. Furthermore, these strengthened FCs of both the dorsal and ventral AI were partially negatively associated with the onset age of blindness. Our result indicates two parallel pathways that selectively transfer non-visual salient information between the deprived "visual" cortex and salience network in blind subjects.

Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin.

To improve the targeting efficacy of hyaluronic acid (HA)-based micelles, pH-sensitive mixed micelles based on HA-g-poly(L-histidine) (PHis) and d-α-tocopheryl polyethylene glycol 2000 copolymers were prepared and decorated with human epidermal growth factor receptor 2 (Her2) peptide, a tumor cell-specific peptide ligand, on their surface. The doxorubicin-loaded micelles (HA-PHis/peptide-d-α-tocopheryl polyethylene glycol 2000 mixed micelles [PHTM]) were characterized to have a unimodal size distribution and pH-dependent drug release pattern. In vitro tumor targeting studies demonstrated that PHTM exhibited the pronounced cytotoxicity and efficient internalization in MDA-MB-231 cells overexpressing CD44 and Her2 receptors. In vivo investigation into micelles in MDA-MB-231 tumor-bearing mice confirmed that PTHM could reach the tumor site more effectively and exert excellent tumor killing activity. In general, Her2 peptide decoration can enhance the selective cytotoxicity and antitumor activity of HA-based micelles.

Non-Gaussian diffusion alterations on diffusion kurtosis imaging in patients with early Alzheimer's disease.

OBJECTIVE: To evaluate non-Gaussian diffusion changes of the whole-brain and its correlation with cognitive performance in patients with early Alzheimer's disease (AD), using diffusion kurtosis imaging (DKI). METHODS: Twenty-six patients with early AD and twenty-six normal controls underwent diffusion imaging. Seven parametric maps were calculated from multiple b-value diffusion data, including mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). Voxel-based analyses were performed to evaluate the group difference between the AD patients and normal controls. Then correlation between the diffusion parameters (MK, FA and MD) and cognitive performance were analyzed in AD patients. RESULTS: For AD patients, increased MD, AxD and RD were found in white matter (WM), including the genu of corpus callosum, bilateral cingulate bundle, bilateral temporal and frontal WM, and were also found in gray matter (GM), including the bilateral temporal GM, parahippocampal gyrus, hippocampus, cingulate gyrus, thalamus, and amygdala. These regions were partially overlapped with those showing decreased FA, MK, AK and RK. However, only kurtosis indices could detect the significant differences in the lentiform nucleus between AD patients and health control. DKI indices in AD patients significantly correlated with the clinical scores in genu of CC, cingulate bundle, temporal and frontal lobe, while the voxel number showing significant correlation with MK was more than that with FA and MD. CONCLUSIONS: Early AD patients already have microstructural changes in both WM and GM. DKI can provide supplementary information in reflecting these changes and may be sensitive in diagnosing early AD.

Assessment of renal allograft function early after transplantation with isotropic resolution diffusion tensor imaging.

OBJECTIVES: To investigate the value of diffusion tensor imaging (DTI) and tractography in renal allografts at the early stage after kidney transplantation. METHODS: This study was approved by the institutional ethical review committee, and written informed consent was obtained. A total of 54 renal allograft recipients 2-3 weeks after transplantation and 26 age-matched healthy volunteers underwent renal DTI with a 3.0-T magnetic resonance imaging (MRI) system. Recipients were divided into three groups according to the estimated glomerular filtration rate (eGFR). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the cortex and medulla were measured and compared among the groups. Whole-kidney tractography was performed. Correlation of eGFR with diffusion parameters was evaluated. RESULTS: In allografts with stable function, the medullary ADC was higher and the cortical FA was lower (p < 0.001) than in healthy kidneys. The cortical ADC, medullary ADC and FA decreased as the allograft function declined, and with a positive correlation with eGFR (p < 0.001); cortical FA did not. Tractography demonstrated a decrease of tract density in impaired functional allografts. CONCLUSIONS: Renal DTI produces reliable results to assess renal allograft function at the early stage after transplantation. KEY POINTS: • DTI and tractography can evaluate renal allograft function at an early stage • Medullary FA, cortical and medullary ADC can effectively evaluate allograft function • Medullary FA, cortical and medullary ADC are correlated with eGFR in renal allografts • Medullary ADC increased and cortical FA decreased in stable allografts compared to control subjects • Medullary FA, cortical and medullary ADC decreased and allograft function declined.

Increased brain iron deposition is a risk factor for brain atrophy in patients with haemodialysis: a combined study of quantitative susceptibility mapping and whole brain volume analysis.

To explore the correlation between increased brain iron deposition and brain atrophy in patients with haemodialysis and their correlation with clinical biomarkers and neuropsychological test. Forty two patients with haemodialysis and forty one age- and gender-matched healthy controls were recruited in this prospective study. 3D whole brain high resolution T1WI and susceptibility weighted imaging were scanned on a 3 T MRI system. The brain volume was analyzed using voxel-based morphometry (VBM) in patients and to compare with that of healthy controls. Quantitative susceptibility mapping was used to measure and compare the susceptibility of different structures between patients and healthy controls. Correlation analysis was used to investigate the relationship between the brain volume, iron deposition and neuropsychological scores. Stepwise multiple regression analysis was used to explore the effect of clinical biomarkers on the brain volumes in patients. Compared with healthy controls, patients with haemodialysis showed decreased volume of bilateral putamen and left insular lobe (All P < 0.05). Susceptibilities of bilateral caudate head, putamen, substantia nigra, red nucleus and dentate nucleus were significantly higher (All P < 0.05). The increased brain iron deposition is negatively correlated with the decreased volume of bilateral putamen (P < 0.01). Neuropsychological scores positively correlated with decreased volume of left insular lobe (P < 0.05). Dialysis duration was negatively associated with decreased volume of bilateral putamen (P < 0.05). Our study indicated increased brain iron deposition and dialysis duration was risk factors for brain atrophy in patients with haemodialysis. The decreased gray matter volume of the left insular lobe was correlated with neurocognitive impairment.

Quantitative Analysis of Diffusion-Weighted Imaging for Diagnosis of Puerperal Breast Abscess After Polyacrylamide Hydrogel Augmentation Mammoplasty: Compared with Other Conventional Modalities.

PURPOSE: Puerperal breast abscess after polyacrylamide hydrogel (PAAG) augmentation mammoplasty can induce breast auto-inflation resulting in serious consequences. Mammography, ultrasound, and conventional MRI are poor at detecting related PAAG abnormality histologically. We evaluated the value of diffusion-weighted imaging (DWI) in the quantitative analysis of puerperal PAAG abscess after augmentation mammoplasty. MATERIALS AND METHODS: This was a retrospective study, and a waiver for informed consent was granted. Sixteen puerperal women with breast discomfort underwent conventional breast non-enhanced MRI and axial DWI using a 3T MR scanner. Qualitative analysis of the signal intensity on DWI and conventional sequences was performed. The apparent diffusion coefficient (ADC) values of the affected and contralateral normal PAAG cysts were measured quantitatively. Paired t test was used to evaluate whether there was significant difference. RESULTS: Both affected and normal PAAG cysts showed equal signal intensity on conventional T1WI and fat saturation T2WI, which were not helpful in detecting puerperal PAAG abscess. However, the affected PAAG cysts had a significantly decreased ADC value of 1.477 ± 0.332 × 10(-3)mm(2)/s and showed obvious hypo-intensity on the ADC map and increased signal intensity on DWI compared with the ADC value of 2.775 ± 0.233 × 10(-3)mm(2)/s of the contralateral normal PAAG cysts. CONCLUSION: DWI and quantitative measurement of ADC values are of great value for the diagnosis of puerperal PAAG abscess. Standardized MRI should be suggested to these puerperal women with breast discomfort or just for the purpose of check up. DWI should be selected as the essential MRI sequence.