NK-92 cells labeled with Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobes for the targeted treatment and noninvasive therapeutic evaluation of breast cancer.

Adoptive cellular immunotherapy as a promising and alternative cancer therapy platform is critical for future clinical applications. Natural killer (NK) cells have attracted attention as an important type of innate immune regulatory cells that can rapidly kill multiple adjacent cancer cells. However, these cells are significantly less effective in treating solid tumors than in treating hematological tumors. Herein, we report the synthesis of a Fe3O4-PEG-CD56/Avastin@Ce6 nanoprobe labeled with NK-92 cells that can be used for adoptive cellular immunotherapy, photodynamic therapy and dual-modality imaging-based in vivo fate tracking. The labeled NK-92 cells specifically target the tumor cells, which increases the amount of cancer cell apoptosis in vitro. Furthermore, the in vivo results indicate that the labeled NK-92 cells can be used for tumor magnetic resonance imaging and fluorescence imaging, adoptive cellular immunotherapy, and photodynamic therapy after tail vein injection. These data show that the developed multifunctional nanostructure is a promising platform for efficient innate immunotherapy, photodynamic treatment and noninvasive therapeutic evaluation of breast cancer.

MR-guided percutaneous microwave coagulation of small breast tumors.

BACKGROUND: To evaluate the technical success and patient safety of magnetic resonance-guided percutaneous microwave coagulation (MR-guided PMC) for breast malignancies. METHODS: From May 2018 to December 2019, 26 patients with breast tumors measuring 2 cm or less were recruited to participate in a prospective, single-institution clinical study. The primary endpoint of this study was the evaluation of treatment efficacy for each patient. Histochemical staining with α-nicotinamide adenine dinucleotide and reduced (NADH)-diaphorase was used to determine cell viability following and efficacy of PMC. The complications and self-reported sensations from all patients during and after ablation were also assessed. The technical success of the PMC procedure was defined when the area of the NADH-diaphorase negative region fully covered the hematoxylin-eosin (H&E) staining region in the tumor. RESULTS: All patients had a complete response to ablation with no residual carcinoma on histopathological specimen. The mean energy, ablation duration, and procedure duration per tumor were 36.0 ± 4.2 kJ, 252.9 ± 30.9 S, and 104.2 ± 13.5 min, respectively. During the ablation, 14 patients underwent prolonged ablation time, and 1 patient required adjusting of the antenna position. Eleven patients had feelings of subtle heat or swelling, and 3 patients experienced slight pain. After ablation, one patient took two painkillers because of moderate pain, and no patients had postoperative oozing or other complications after PMC. Induration around the ablation area appeared in 16 patients. CONCLUSION: MR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future. CRITICAL RELEVANCE STATEMENT: MR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future. KEY POINTS: • MR-guided PMC of small breast tumors is feasible. • PMC was successfully performed for all patients. • All patients were satisfied with the final cosmetic result.

Prognostic value of amino acid metabolism-related gene expression in invasive breast carcinoma.

BACKGROUND: An increasing number of studies indicated that metabolic reprogramming of amino acid metabolism may either promote or inhibit tumor progression. The purpose of this study was to investigate the ability of a gene risk signature associated with amino acid metabolism to predict the prognosis and immune characteristics of invasive breast carcinoma. METHODS: LASSO Cox regression analysis was performed to construct and validate the prognostic risk signature based on the expression of 9 amino acid metabolism-related genes. The predictive value of the signature, immune characteristics, and chemotherapeutic drugs was also predicted. Finally, 9 significant genes were examined in MDA-MB-231 and MCF-7 cells, and the predicted chemotherapeutic drugs were also verified. RESULTS: The prognosis of the low-risk group was better than that of the high-risk group. The areas under the curve (AUCs) at 1, 2, and 3 years were 0.852, 0.790, and 0.736, respectively. In addition, the GSEA results for KEGG and GO revealed that samples with a high-risk score exhibited a variety of highly malignant manifestations. The high-risk group was characterized by an increased number of M2 macrophages, a high level of tumor purity, low levels of APC co-stimulation, cytolytic activity, HLA, para-inflammation, and type I IFN response. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) confirmed that MDA-MB-231 and MCF-7 cells express 9 amino acid metabolism-related genes differently. In addition, cell experiments were conducted to examine the effect of cephaeline-induced on cell viability, migration ability, and protein expression of the PI3K/AKT signaling pathway and HIF-1α. CONCLUSION: We established a risk signature based on 9 amino acid metabolism-related genes for invasive breast carcinoma. Further analyses revealed that this risk signature is superior to other clinical indexes in survival prediction and that the subgroups identified by the risk signature exhibit distinct immune characteristics. Cephaeline was determined to be a superior option for patients in high-risk groups.

Application of advanced diffusion models from diffusion weighted imaging in a large cohort study of breast lesions.

BACKGROUND: To evaluate multiple parameters in multiple b-value diffusion-weighted imaging (DWI) in characterizing breast lesions and predicting prognostic factors and molecular subtypes. METHODS: In total, 504 patients who underwent 3-T magnetic resonance imaging (MRI) with T1-weighted dynamic contrast-enhanced (DCE) sequences, T2-weighted sequences and multiple b-value (7 values, from 0 to 3000 s/mm2) DWI were recruited. The average values of 13 parameters in 6 models were calculated and recorded. The pathological diagnosis of breast lesions was based on the latest World Health Organization (WHO) classification. RESULTS: Twelve parameters exhibited statistical significance in differentiating benign and malignant lesions. alpha demonstrated the highest sensitivity (89.5%), while sigma demonstrated the highest specificity (77.7%). The stretched-exponential model (SEM) demonstrated the highest sensitivity (90.8%), while the biexponential model demonstrated the highest specificity (80.8%). The highest AUC (0.882, 95% CI, 0.852-0.912) was achieved when all 13 parameters were combined. Prognostic factors were correlated with different parameters, but the correlation was relatively weak. Among the 6 parameters with significant differences among molecular subtypes of breast cancer, the Luminal A group and Luminal B (HER2 negative) group had relatively low values, and the HER2-enriched group and TNBC group had relatively high values. CONCLUSIONS: All 13 parameters, independent or combined, provide valuable information in distinguishing malignant from benign breast lesions. These new parameters have limited meaning for predicting prognostic factors and molecular subtypes of malignant breast tumors.

A Review of Breast Density Implications and Breast Cancer Screening.

Breast density is an independent risk factor for breast cancer and significantly decreases the sensitivity of mammography. Assessing a woman's risk of developing breast cancer is becoming increasingly important for establishing individual screening recommendations and preventive strategies. This article reviews the factors influencing mammographic density (MD), the available methods of MD assessment, and its effect on breast cancer. Finally, we discuss the supplemental screening methods for women with dense breast tissue.

Histogram analysis of diffusion kurtosis imaging based on whole-volume images of breast lesions.

BACKGROUND: Breast diffusion kurtosis imaging (DKI) is a novel MRI technique to assess breast cancer but the effectivity still remains to be improved. PURPOSE: To investigate the performance of whole-volume histogram parameters derived from a DKI model for differentiating benign and malignant breast lesions. STUDY TYPE: Retrospective. POPULATION: In all, 120 patients with breast lesions (62 malignant, 58 benign). SEQUENCE: DKI sequence with seven b-values (0, 500, 1000, 1500, 2000, 2500, and 3000 s/mm2 ) and DWI sequence with two b-values (0 and 1000 s/mm2 ) on 3.0T MRI. ASSESSMENT: Histogram parameters of the DKI model (K and D) and the DWI model (ADC), including the minimum, maximum, mean, percentile values (25th, 50th, 75th, and 95th), standard deviation, kurtosis and skewness, were calculated by two radiologists for the whole lesion volume. STATISTICAL TESTS: Student's t-test was used to compare malignant and benign lesions. The diagnostic performances were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: Kmax , Dmin , and ADCmin had the highest area under the curve (AUC) (0.875, 0.830, and 0.847, respectively), sensitivity (85.5%, 74.2%, and 77.4%, respectively), and accuracy (85.0%, 79.2%, and 81.7%, respectively) in their individual histogram parameter groups, and Kmax was found to outperform Dmin and ADCmin . ADC histogram parameters (from ADCmin to ADCsd ) were significantly lower than D histogram parameters in all groups. DATA CONCLUSION: Kmax , Dmin , and ADCmin were found to be better metrics than the corresponding average values for differentiating benign from malignant tumors. Histogram parameters derived from the DKI model provided more information and had better diagnostic performance than ADC parameters derived from the DWI model. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:627-634.

White matter impairment in type 2 diabetes mellitus with and without microvascular disease.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a serious public health problem, and the phenomenon of T2DM occurring in younger people has directed more attention to functional changes in the brain. In this study, the microstructural integrity of white matter (WM) was evaluated in three groups of middle-aged subjects: healthy controls (HCs) and T2DM patients with and without peripheral microvascular complications (T2DM-C and T2DM-NC patients, respectively). METHODS: Diffusion tensor imaging (DTI) and related clinical examinations were performed in 66 subjects, including 20 T2DM-C patients, 20 T2DM-NC patients, 26 age- and sex-matched HCs. Magnetic resonance imaging (MRI) at 3 T was used to perform DTI; then, FSL and tract-based spatial statistics (TBSS) software were used to assess differences in the fractional anisotropy (FA) and mean diffusivity (MD) among the groups. The use of the FA and MD as parameters was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: There were no significant differences in sex or age among the groups, and the clinical data of the groups met the experimental requirements. There was no significant difference in the FA values between the HCs and T2DM-NC groups. Compared with the HCs, the T2DM-C patients showed decreased FA values and increased MD values in the corpus callosum, bilateral anterior limb of the internal capsule, right retrolenticular part of the internal capsule, bilateral posterior thalamic radiation, right superior longitudinal fasciculus, bilateral superior corona radiata and left middle frontal gyrus (P < .01). Compared with the T2DM-NC patients, the T2DM-C patients showed decreased FA values and increased MD values in the corpus callosum, bilateral fornix, right retrolenticular part of the internal capsule, middle cerebral peduncle, right superior longitudinal fasciculus, right posterior thalamic radiation, and left middle frontal gyrus (P < .01). CONCLUSIONS: This study indicates that WM impairment is present in T2DM patients and may be related to microvascular complications. More importantly, this study also shows that such impairment may be diagnosed using the DTI mode of functional MRI before it can be diagnosed clinically.

Magnetic Resonance Imaging of the Human Ferritin Heavy Chain Reporter Gene Carried by Dendrimer-Entrapped Gold Nanoparticles.

This paper aimed to find an effective method to destroy cancer cells by targeting breast cancer cells with natural killer (NK) cells transfected with the human ferritin heavy chain (hFTH1) gene by polyethylene glycol (PEG)-modified dendrimerentrapped gold nanoparticles (Au DENPs). In this study, fifth-generation polyamidoamine (G5 PAMAM) dendrimers modified with PEG were used as templates to entrap gold nanoparticles to transfect hFTH1 into NK cells. Our results revealed that the prepared Au DENPs/FTH1 provided high-quality imaging performance (hypointensity on T2-weighted MR imaging) and efficient transfection efficiency (reaching 80.2%) at a N/P ratio (ratio of the number of surface primary amines on {(Au0)25-G5 · NH2-mPEG17} to the number of phosphate groups in the hFTH1 backbone) of 5:1. Interestingly, the results showed that Au DENPs/FTH1 effectively guided NK-92 cells to concentrate around tumor cells for effective gene therapy without severely impacting their activity. This work will provide a new research platform for immunotherapy based on NK cells and lead to the optimization and even individualization of breast cancer immunotherapy through nanomolecular visualization research, which has a broad scope for future clinical applications.

Compensatory Hippocampal Connectivity in Young Adults With Early-Stage Type 2 Diabetes.

CONTEXT: Middle-aged to elderly patients with type 2 diabetes mellitus (T2DM) exhibit reduced functional connectivity and brain atrophy underlying cognitive decrements; however, little is known about brain abnormalities in young patients. OBJECTIVE: To detect brain anatomical and functional changes in young patients with T2DM during the early disease stage. DESIGN: Case-control study. SETTING: Tertiary referral hospital. PARTICIPANTS: Thirty-five young patients with T2DM (<40 years of age) with no detectable microangiopathy and 32 nondiabetic control subjects. INTERVENTION: None. MAIN OUTCOME MEASURES: Subjects underwent neuropsychological assessments and structural and resting-state functional MRI. Both voxel-based morphometry and resting-state functional connectivity analyses were performed. RESULTS: No significant differences in brain volume were observed between the patients with T2DM and the controls after controlling for age, sex, education, and body mass index. Compared with the controls, the patients showed greater connectivity of the left hippocampus with the left inferior frontal gyrus and the left inferior parietal lobule. Moreover, the enhanced functional connectivity of left hippocampus with the left inferior frontal gyrus significantly correlated with disease severity (urinary albumin-to-creatinine ratio) (r = 0.613, P < 0.001) and executive function (completion time of Stroop Color and Word Test) (r = -0.461, P = 0.005) after false discovery rate correction. CONCLUSIONS: Our findings suggest an adaptive compensation of brain function to counteract the insidious cognitive decrements during the early stage of T2DM. Additionally, the functional alterations occurring before changes in brain structure and peripheral microangiopathy might serve as early biomarkers related to cognitive decrements.

Use of diffusion kurtosis imaging and quantitative dynamic contrast-enhanced MRI for the differentiation of breast tumors.

BACKGROUND: Breast MRI is a sensitive imaging technique to assess breast cancer but its effectiveness still remains to be improved. PURPOSE: To evaluate the diagnostic performance of diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI), and quantitative dynamic contrast-enhanced (DCE)-MRI in differentiating malignant from benign breast lesions independently or jointly and to explore whether correlations exist among these parameters. STUDY TYPE: Retrospective. POPULATION: In all, 106 patients with breast lesions (47 malignant, 59 benign). SEQUENCE: DKI sequence with seven b values and quantitative DCE sequence on 3.0T MRI. ASSESSMENT: Diffusion parameters (mean diffusivity [MD], mean diffusivity [MK], and apparent diffusion coefficient [ADC]) from DKI and DWI and perfusion parameters from DCE (Ktrans , kep , ve , and vp ) were calculated by two experienced radiologists after postprocessing. Disagreement between the two observers was resolved by consensus. STATISTICAL TESTS: The parameters in benign and malignant lesions were compared by Student's t-test. The diagnostic performances of DKI and quantitative DCE, either alone or in combination, were evaluated by receiver operating characteristic (ROC) analysis. The Spearman correlation test was used to evaluate correlations among the diffusion parameters and perfusion parameters. RESULTS: MK, MD, ADC, Ktrans , and kep values were significantly different between breast cancer and benign lesions (P < 0.05). MK from DKI demonstrated the highest AUC of 0.849, which is significantly higher than ADC derived from conventional DWI (z = 3.345, P = 0.0008). The specificity of DCE-MRI-derived parameters was improved when combining diffusion parameters, such as ADC and MK. The highest diagnostic specificity (93.2%) was obtained when kep and ADC were combined. kep was correlated moderately positively with MK (r = 0.516) and moderately negatively with MD (r = -0.527). Ktrans was weakly positively correlated with MK with an r of 0.398 and weakly negatively correlated with MD with an r of -0.450. DATA CONCLUSION: DKI is more valuable than conventional DWI in distinguishing between benign and malignant breast lesions. DKI exhibits promise as a quantitative technique to augment quantitative DCE-MRI. Diffusion parameters derived from DKI were statistically correlated with perfusion parameters from quantitative DCE-MRI. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1358-1366.

Brain atrophy in middle-aged subjects with Type 2 diabetes mellitus, with and without microvascular complications.

BACKGROUND: The rapid rise in Type 2 diabetes mellitus (T2DM) among young adults makes it important to understand structural changes in the brain at a presenile stage. This study examined global and regional brain atrophy in middle-aged adults with T2DM, with a focus on those without clinical evidence of microvascular complications. METHODS: The study recruited 66 dementia-free middle-aged subjects (40 with T2DM, 26 healthy volunteers [HVs]). Patients were grouped according to the presence (T2DM-C; n = 20) or absence (T2DM-NC; n = 20) of diabetic microvascular complications. Global brain volume (including gray matter [GM] and white matter) was calculated based on voxel-based morphometry analysis. Regional GM volumes were further extracted using the anatomical automatic labeling template. RESULTS: There was a significant difference in global brain volume among groups (P = 0.003, anova). Global brain volume was lower in T2DM-C patients than in both T2DM-NC patients and HVs (mean [±SD] 0.720 ± 0.024 vs 0.736 ± 0.021 and 0.743 ± 0.019, respectively; P = 0.032 and P = 0.001, respectively). Regional analysis showed significant GM atrophy in the right Rolandic operculum (t = 3.42, P = 0.001) and right superior temporal gyrus (t = 2.803, P = 0.007) in T2DM-NC patients compared with age- and sex-matched HVs. CONCLUSIONS: Brain atrophy is present in dementia-free middle-aged adults with T2DM. Regional brain atrophy appears to be developing even in those with no clinical evidence of microvascular disturbances. The brain seems to be particularly vulnerable to metabolic disorders prior to peripheral microvascular pathologies associated with other target organs.

Combined resting state functional magnetic resonance imaging and diffusion tensor imaging study in patients with idiopathic restless legs syndrome.

OBJECTIVE: Restless legs syndrome (RLS) is a common neurological disorder characterized by an urge to move the legs along with paraesthesia deep within them. In this study, we aimed to use diffusion tensor imaging (DTI) and regional homogeneity (ReHo) to investigate the changes in regional spontaneous brain activity change for RLS patients against age- and gender-matched normal control (NC) subjects. METHODS: A total of 35 RLS patients and 27 age- and gender-matched NC subjects were recruited for group comparison research that used DTI and ReHo techniques. DTI was analysed by FSL and tract-based spatial statistics (TBSS) software to measure the values of fractional anisotropy (FA) or mean diffusivity (MD) in brain regions. Statistical Parametric Mapping 8 (SPM8) was used for data preprocessing and Data Processing Assistant for Resting-State fMRI (DPARSF) toolbox was used for ReHo calculation. For multiple comparison correction, the AlphaSim program implemented in AFNI was used to control the false-positive rate (corrected p < 0.05). RESULTS: There was no significant difference between the iRLS and NC groups in age or gender. In the one-sample t-test, both the NC and RSL groups showed increased ReHo in the bilateral posterior cingulate/precuneus cortex compared to the groups' global means, indicating that the default mode network was at rest. The RLS group showed a smaller cluster size than the NC group. In the two-sample t-test, the RLS group showed increased ReHo in the bilateral middle frontal gyrus, anterior cingulate cortex, caudate nucleus, insula, thalamus, putamen and left posterior cingulate cortex compared to the NC group. The statistical analysis of DTI images did not show any difference between the two groups. TBSS group comparison did not reveal any difference in FA or mean diffusivity (MD) of any brain region. CONCLUSION: RLS patients showed that greater ReHo within the striatum, thalamus and the limbic system, which implies that the emotional processing, motion control and cognition in the cortico-striatal-thalamic-cortical (CSTC) loop may be the site of dysfunction in RLS patients. This finding may provide imaging evidence to explore the pathophysiology of RLS. On the other hand, we did not see any change in the microstructure in the DTI analysis for RLS patients when compared to the NC group, which suggests a metabolic impairment.

Differentiation between adrenal adenomas and nonadenomas using dynamic contrast-enhanced computed tomography.

This study was performed to evaluate the findings including the time density curve (TD curve), the relative percentage of enhancement washout (Washr) and the absolute percentage of enhancement washout (Washa) at dynamic contrast-enhanced computed tomography (DCE-CT) in 70 patients with 79 adrenal masses (including 44 adenomas and 35 nonadenomas) confirmed histopathologically and/or clinically. The results demonstrated that the TD curves of adrenal masses were classified into 5 types, and the type distribution of the TD curves was significantly different between adenomas and nonadenomas. Types A and C were characteristic of adenomas, whereas types B, D and E were features of nonadenomas. The sensitivity, specificity and accuracy for the diagnosis of adenoma based on the TD curves were 93%, 80% and 87%, respectively. Furthermore, when myelolipomas were excluded, the specificity and accuracy for adenoma were 90% and 92%, respectively. The Washr and the Washa values for the adenomas were higher than those for the nonadenomas. The diagnostic efficiency for adenoma was highest at 7-min delay time at DCE-CT; Washr was more efficient than Washa. Washr ≥34% and Washa ≥43% were both suggestive of adenomas and, on the contrary, suspicious of nonadenomas. The sensitivity, specificity and accuracy for the diagnosis of adenoma were 84%, 77% and 81%, respectively. When myelolipomas were precluded, the diagnostic specificity and accuracy were 87% and 85%, respectively. Therefore, DCE-CT aids in characterization of adrenal tumors, especially for lipid-poor adenomas which can be correctly categorized on the basis of TD curve combined with the percentage of enhancement washout.

Preclinical study of diagnostic performances of contrast-enhanced spectral mammography versus MRI for breast diseases in China.

PURPOSE: To evaluate diagnostic performances of CESM for breast diseases with comparison to breast MRI in China. MATERIALS AND METHODS: Sixty-eight patients with 77 breast lesions underwent MR and CESM. Two radiologists interpreted either MRI or CESM images, separately and independently. BI-RADS 1-3 and BI-RADS 4-5 were classified into the suspicious benign and suspicious malignant groups. Diagnostic accuracy parameters were calculated. Receiver operating characteristic (ROC) curves were constructed for the two modalities. The agreement and correlation between maximum lesion diameter based on CESM and MRI, or CESM and pathology were analyzed. RESULTS: Diagnostic accuracy parameters for CESM were sensitivity 95.8 %, specificity 65.5 %, PPV 82.1 %, NPV 90.5 % and accuracy 84.4 %. The diagnostic accuracy parameters for breast MRI were sensitivity 93.8 %, specificity 82.8 %, PPV 88.2 %, NPV 92.3 %and accuracy 89.6 %. Area under the curve (AUC) of ROC was 0.96 for breast MRI and 0.88 for CESM. The Bland-Altman plots showed a mean difference of 0.7 mm with 95 % limits of agreement of 11.4 mm in tumor diameter measured using CESM and breast MRI. The differences of size measurement between CESM and breast MRI were significant, whereas no difference was observed between CESM and pathology as well as between breast MRI and pathology. The better correlation with pathological results was found in CESM than breast MRI. CONCLUSION: Our study demonstrates that CESM possesses better diagnostic performances than breast MRI in terms of diagnostic sensitivity and lesion size assessment. And CESM is a good alternative method of screening breast cancer in high-risk people.

Tumoral angiogenesis in both adrenal adenomas and nonadenomas: a promising computed tomography biomarker for diagnosis.

To explore the correlation between the typical findings of dynamic contrast-enhanced computed tomography (DCE-CT) and tumoral angiogenesis (microvessel density [MVD] and vascular endothelial growth factor [VEGF]) in adenomas and nonadenomas such that the enhancement mechanism of DCE-CT in adrenal masses can be explained more precisely. Forty-two patients with 46 adrenal masses confirmed by surgery and pathology were included in the study; these masses included 23 adenomas, 18 nonadenomas, and 5 hyperplastic nodules. The findings of DCE-CT and angiogenesis in adrenal masses were studied. The features of DCE-CT in adenomas and nonadenomas were evaluated to determine whether the characteristics of DCE-CT in adrenal masses were closely correlated with tumoral angiogenesis. Adrenal adenomas were significantly different from nonadenomas in the time density curve and the mean percentage of enhancement washout at the 7-minute delay time in DCE-CT. The mean MVD and VEGF expression exhibited significant differences between the rapid washout group (types A and C) and the slow washout group (types B, D, and E) and between the relative washout (Washr) ≥34% and the absolute washout (Washa) ≥43% on the 7-minute enhanced CT scans (P=0.000). Adenomas were suggested when adrenal masses presented as types A and C, and/or the Washr ≥34%, and/or the Washa ≥43%, and the opposite was suggested for nonadenomas. These results showed a close correlation between the characteristics of DCE-CT and both MVD and VEGF expression in adrenal masses. There was also a significant difference in MVD and VEGF expression between adenomas and nonadenomas. In conclusion, MVD and VEGF expression are two important pathological factors that play important roles in the characterization of DCE-CT in adrenal masses because they cause different time density curve types, the Washr and the Washa for adrenal adenomas and nonadenomas.

Arg-Gly-Asp-D-Phe-Lys peptide-modified PEGylated dendrimer-entrapped gold nanoparticles for targeted computed tomography imaging of breast carcinoma.

AIM: To investigate cyclo (Arg-Gly-Asp-D-Phe-Lys) peptide (RGD)-modified PEGylated dendrimer-entrapped gold nanoparticles (PEGylated Au DENPs-RGD) for targeted computed tomography (CT) imaging of breast carcinomas. MATERIALS & METHODS: PEGylated Au DENPs-RGD were synthesized and characterized. Then, the PEGylated Au DENPs-RGD for targeted CT imaging were investigated using the MDA-MB-435 cell line, an integrin-rich breast carcinoma cells, and mice with MDA-MB-435 xenograft tumors. Finally, silver enhancement staining and integrin αvß3 immunohistochemistry of the tumors were performed. RESULTS: The synthesized PEGylated Au DENPs-RGD were spherical, water dispersible and biocompatible nanoprobes with a gold nanoparticle core size of 2.8 nm. Due to the presence of the Au nanoparticles, the PEGylated Au DENPs-RGD displayed a higher x-ray attenuation intensity than Omnipaque at the same Au or I concentrations. The conjugated RGD ligand can specifically identify and target overexpressed integrin receptors on MDA-MB-435 cells. After intravenous injection, these nanoprobes accumulated in the targeted area of mice with MDA-MB-435 xenograft tumors, which enabled the tumor to be detected by CT imaging. The histological results confirmed the imaging results. CONCLUSION: The PEGylated Au DENPs-RGD can be used as targeted nanoprobes with good biocompatibility for targeted CT imaging and diagnosis of integrin-positive tumors.

Dendrimer-Assisted Formation of Fe3O4/Au Nanocomposite Particles for Targeted Dual Mode CT/MR Imaging of Tumors.

A unique dendrimer-assisted approach is reported to create Fe3O4/Au nanocomposite particles (NCPs) for targeted dual mode computed tomography/magnetic resonance (CT/MR) imaging of tumors. In this approach, preformed Fe3O4 nanoparticles (NPs) are assembled with multilayers of poly(γ-glutamic acid) (PGA)/poly(L-lysine)/PGA/folic acid (FA)-modified dendrimer-entrapped gold nanoparticles via a layer-by-layer self-assembly technique. The interlayers are crosslinked via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide chemistry, the assembled Au core NPs are then used as seed particles for subsequent seed-mediated growth of Au shells via iterative Au salt reduction process, and subsequent acetylation of the remaining amines of dendrimers leads to the formation of Fe3O4/Au(n.)Ac-FA NCPs with a tunable molar ratio of Au/Fe3O4. It is shown that the Fe3O4/Au(n.)Ac-FA NCPs at an optimized Au/Fe3O4 molar ratio of 2.02 display a relatively high R2 relaxivity (92.67 × 10(-3) M(-1) s(-1)) and good X-ray attenuation property, and are cytocompatible and hemocompatible in the given concentration range. Importantly, with the FA-mediated targeting, the Fe3O4/Au(n.)Ac-FA NCPs are able to be specifically uptaken by cancer cells overexpressing FA receptors, and be used as an efficient nanoprobe for targeted dual mode CT/MR imaging of a xenografted tumor model. With the versatile dendrimer chemistry, the developed Fe3O4/Au NCPs may be differently functionalized, thereby providing a unique platform for diagnosis and therapy of different biological systems.

Clinically applicable magnetic-labeling of natural killer cells for MRI of transcatheter delivery to liver tumors: preclinical validation for clinical translation.

AIM: To test the hypothesis that MRI can monitor intraportal vein (IPV) transcatheter delivery of clinically applicable heparin-protamine-ferumoxytol (HPF) nanocomplex-labeled natural killer (NK) cells to liver tumor. MATERIALS & METHODS: Liver tumor rat models underwent catheterization for IPV infusion of HPF-labeled NK cells (NK-92MI cell line). MRI measurements within tumor and adjacent liver tissues were compared pre- and post-NK cell infusion. Histology studies were used to identify NK cells in the target tumors. RESULTS: For first time, we demonstrated that MRI tracks HPF-labeled NK cells migration within liver following IPV delivery. CONCLUSION: IPV transcatheter infusion permitted selective delivery of NK cells to liver tissues and MRI allowed tracking NK cell biodistributions within the tumors.

Imaging quality evaluation of low tube voltage coronary CT angiography using low concentration contrast medium.

PURPOSE: To compare the image quality of prospectively ECG-gated low voltage coronary computed tomography angiography (CTA) with an administration of low concentration contrast medium. METHOD AND MATERIALS: A total of 101 patients, each with a heart rate below 65 beats per minute (BPM), underwent a prospectively ECG-gated axial scan in CT coronary angiography on a 64-slice CT scanner. All patients were allocated in three groups (group A: n=31, 80 kVp, 300 mgI/ml; group B: n=34, 100 kVp, 300 mgI/ml; group C: n=36, 120 kVp, 370 mgI/ml). The CT attenuation values of aortic root (AR), left main coronary artery (LMA), right main coronary artery (RMA) and chest subcutaneous fat tissue were measured. The contrast-to-noise ratio (CNR) of AR, LMA and RMA were calculated according to the formulas below. The values of computed tomography dose index (CTDI) and dose-length product (DLP) were recorded. Image quality was assessed on a 5-point scale. The results were compared using the one-way ANOVA and rank sum tests. RESULTS: The values of CNR and SNR for vessels in group A and group B were not significantly different from group C (each p > 0.05). The effective radiation dose in group A (1.51 ± 0.70 mSv) and group B (2.59 ± 1.24 mSv) were both lower than group C (4.92 ± 2.82 mSv) (each p < 0.05). There was no significant difference among the image quality scores of group A (4.10 ± 0.41), group B (3.90 ± 0.48) and group C (4.04 ± 0.36) (each P > 0.05). CONCLUSION: Low tube voltage coronary CT angiography using low concentration contrast medium does not affect the imaging quality for assessing the coronary arteries compared with high voltage coronary CT angiography using high concentration contrast medium. Meanwhile low concentration contrast medium allowed 47-69% of radiation dose reduction.

Respiratory self-gating for free-breathing magnetization transfer MRI of the abdomen.

PURPOSE: Magnetization transfer (MT) MRI can be effective for the diagnosis of a broad range of fibrotic diseases, including liver fibrosis. However, respiratory motion, a major source of artifacts in thoracic and abdominal MR imaging, can obscure important anatomic structures, making diagnosis difficult. In this study, we explored the potential to combine free-breathing (FB) respiratory self-gating (RSG) methods with MT saturation for FB MT ratio (MTR) measurements of abdominal organs. METHODS: A respiratory self-gated multiple-gradient recalled echo sequence with MT presaturation (RSG-MT GRE) was developed and applied in a series of seven normal volunteers. We compared the MTR values of liver, pancreas, kidney, spleen, and posterior paraspinal muscle measured using our RSG-MT GRE sequence and a conventional MT GRE sequence. RESULTS: RSG consistently reduced motion artifacts within MT-weighted images acquired during FB, improved the accuracy of FB MTR measurements, and produced comparable MTRs to breath-holding MTR measurements. CONCLUSION: RSG approaches may offer to improve the utility of MT-weighted imaging methods for the assessment of fibrotic diseases and tumor desmoplasia in abdominal organs.