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.

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.

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.

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.

Antigen-loaded dendritic cell migration: MR imaging in a pancreatic carcinoma model.

PURPOSE: To test the following hypotheses in a murine model of pancreatic cancer: (a) Vaccination with antigen-loaded iron-labeled dendritic cells reduces T2-weighted signal intensity at magnetic resonance (MR) imaging within peripheral draining lymph nodes ( LN lymph node s) and (b) such signal intensity reductions are associated with tumor size changes after dendritic cell vaccination. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. Panc02 cells were implanted into the flanks of 27 C57BL/6 mice bilaterally. After tumors reached 10 mm, cell viability was evaluated, and iron-labeled dendritic cell vaccines were injected into the left hind footpad. The mice were randomly separated into the following three groups (n = 9 in each): Group 1 was injected with 1 million iron-labeled dendritic cells; group 2, with 2 million cells; and control mice, with 200 mL of phosphate-buffered saline. T1- and T2-weighted MR imaging of labeled dendritic cell migration to draining LN lymph node s was performed before cell injection and 6 and 24 hours after injection. The signal-to-noise ratio ( SNR signal-to-noise ratio ) of the draining LN lymph node s was measured. One-way analysis of variance ( ANOVA analysis of variance ) was used to compare Prussian blue-positive dendritic cell measurements in LN lymph node s. Repeated-measures ANOVA analysis of variance was used to compare in vivo T2-weighted SNR signal-to-noise ratio LN lymph node measurements between groups over the observation time points. RESULTS: Trypan blue assays showed no significant difference in mean viability indexes (unlabeled vs labeled dendritic cells, 4.32% ± 0.69 [standard deviation] vs 4.83% ± 0.76; P = .385). Thirty-five days after injection, the mean left and right flank tumor sizes, respectively, were 112.7 mm(2) ± 16.4 and 109 mm(2) ± 24.3 for the 1-million dendritic cell group, 92.2 mm(2) ± 9.9 and 90.4 mm(2) ± 12.8 for the 2-million dendritic cell group, and 193.7 mm(2) ± 20.9 and 189.4 mm(2) ± 17.8 for the control group (P = .0001 for control group vs 1-million cell group; P = .00007 for control group vs 2-million cell group). There was a correlation between postinjection T2-weighted SNR signal-to-noise ratio decreases in the left popliteal LN lymph node 24 hours after injection and size changes at follow-up for tumors in both flanks (R = 0.81 and R = 0.76 for left and right tumors, respectively). CONCLUSION: MR imaging approaches can be used for quantitative measurement of accumulated iron-labeled dendritic cell-based vaccines in draining LN lymph node s. The amount of dendritic cell-based vaccine in draining LN lymph node s correlates well with observed protective effects.

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.

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.

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.

Magnetic resonance imaging monitoring dual-labeled stem cells for treatment of mouse nerve injury.

BACKGROUND AIMS: Adipose-derived stem cells (ADSCs) have shown great promise in the regenerative repair of injured peripheral nerves. Magnetic resonance imaging (MRI) has provided attractive advantages in tracking superparamagnetic iron oxide nanoparticle (SPION)-labeled cells and evaluating their fate after cell transplantation. This study investigated the feasibility of the use of MRI to noninvasively track ADSCs repair of peripheral nerve injury in vivo. METHODS: Green fluorescent protein (GFP)-expressing ADSCs were isolated, expanded, differentiated into an SC-like phenotype (GFP-dADSCs) at early passages and subsequently labeled with SPIONs. The morphological and functional properties of the GFP-dADSCs were assessed through the use of immunohistochemistry. The intracellular stability, proliferation and viability of the labeled cells were evaluated in vitro. Through the use of a microsurgical procedure, the labeled cells were then seeded into sciatic nerve conduits in C57/BL6 mice to repair a 1-cm sciatic nerve gap. A clinical 3-T MRI was performed to investigate the GFP-dADSCs in vitro and the transplanted GFP-dADSCs inside the sciatic nerve conduits in vivo. RESULTS: The GFP-dADSCs were efficiently labeled with SPIONs, without affecting their viability and proliferation. The labeled cells implanted into the mice sciatic nerve conduit exhibited a significant increase in axonal regeneration compared with the empty conduit and could be detected by MRI. Fluorescent microscopic examination, histological analysis and immunohistochemistry confirmed the axon regeneration and MRI results. CONCLUSIONS: These data will elucidate the neuroplasticity of ADSCs and provide a new protocol for in vivo tracking of stem cells that are seeded to repair injured peripheral nerves.

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.

Facile one-pot preparation, surface functionalization, and toxicity assay of APTS-coated iron oxide nanoparticles.

We report a facile approach to synthesizing 3-aminopropyltrimethoxysilane (APTS)-coated magnetic iron oxide (Fe(3)O(4)@APTS) nanoparticles (NPs) with tunable surface functional groups for potential biomedical applications. The Fe(3)O(4) NPs with a mean diameter of 6.5 nm were synthesized by a hydrothermal route in the presence of APTS. The formed amine-surfaced Fe(3)O(4)@APTS NPs were further chemically modified with acetic anhydride and succinic anhydride to generate neutral (Fe(3)O(4)@APTS⋅Ac) and negatively charged (Fe(3)O(4)@APTS⋅SAH) NPs. These differently functionalized NPs were extensively characterized by x-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetry analysis, zeta potential measurements, and T(2) relaxometry. The cytotoxicity of the particles was evaluated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric viability assay of cells along with microscopic observation of cell morphology. The hemocompatibility of the particles was assessed by in vitro hemolysis assay. We show that the hydrothermal approach enables an efficient modification of APTS onto the Fe(3)O(4) NP surfaces and the formed NPs with different surface charge polarities are water-dispersible and colloidally stable. The acetylated Fe(3)O(4)@APTS⋅Ac NPs displayed good biocompatibility and hemocompatibility in the concentration range of 0-100 µg ml(-1), while the pristine Fe(3)O(4)@APTS and Fe(3)O(4)@APTS⋅SAH particles started to display slight cytotoxicity at a concentration of 10 µg ml(-1). The findings from this study suggest that the Fe(3)O(4)@APTS NPs synthesized by the one-pot hydrothermal route can be surface modified for various potential biomedical applications.

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.

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.

[MRI monitoring of cerebral spinal fluid metastasis in rabbit model].

OBJECTIVE: To establish a rabbit model of cerebral spinal flow metastasis, to analyze the growth rate of tumor, and to investigate the value of MRI in monitoring the biology of tumor compared with pathology. METHODS: Twenty-four New Zealand white rabbits were inoculated with suspension of VX(2) tumor cells in the subarachnoid space via the foramen magnum (experimental group), and 6 rabbits were inoculated with normal saline (control group). MRI examination, including non-enhanced T(1)WI, T(2)WI, and FLAIR sequences and then T(1)WI, FLAIR after dynamic contrast enhanced with Gd-DTPA were done 7 approximately 22 days after inoculation with a 3-day interval. The rabbits were killed after the last MRI scan with their spinal cords, spinal meninges, and tumor taken out to undergo microscopy. RESULTS: (1) MRI plain scan showed that in the experimental group 2 nodi in the medulla and 1 nodes in the cervical spinal cord were found with low signal on T(1)WI and high signal on T(2)WI; and FLAIR imaging showed local lesions with medial signal in 6 rabbits (25%). And no abnormal signs were seen in the control group. (2) MRI enhancement showed that in the experimental group the images of 15 rabbit models were enhanced markedly with irregular thickening of meninges or nodules at the subarachnoid space on T(1)WI, positive signs were confirmed on FLAIR sequence in 16 of the 24 rabbits, and positive signs were noted on DCE-MRI scanning in 18 of the 24 rabbits (75%). In the control group 5 of the 6 rabbits were negative in images. Microscopy showed thickened of meninges and spinal meninges in 20 of the 24 rabbits of the experimental group and spinal cord metastasis in 22 rabbits. No pathological changes were seen in the control group. Statistics showed a CSF metastasis rate of 91.67%. There were significant difference between the plain scan and T(1)WI with enhancement (P < 0.01) and between FLAIR scan and FLAIR enhancement scans. There was a significant difference between T(1)WI and FLAIR enhancement and pathological findings (P < 0.05). There was no significant difference between DCE-MRI method and pathological results (P > 0.05). CONCLUSION: Gd-DTPA enhanced MRI scan sequences has a high sensitivity and specificity and can be used in monitoring the growth of CSF metastasis. There is a disparity between the MRI signs and pathological findings. It is a key that to improve the spatial resolution of machine and to investigate the best method for detecting early metastasis.

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.

[MRI monitoring ultra-small superparamagnetic iron oxide (USPIO) particle labeling C6 rat glioma cells].

OBJECTIVE: To monitor the effects of labeling C6 rat glioma cells with different concentrations of USPIO in vivo and in vitro. METHODS: C6 rat glioma cells of 1 x 10(6), 2 x 10(6) and 1 x 10(7) were labeled with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO, The signal intensity of cells were evaluated by MRI with T(1)WI, T(2)WI and GRE/30 degrees sequences in vitro. 1 x 10(6) of C6 glioma cells were labeled with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO and inoculated into the right frontal lobe of 2 rats under stereotaxis apparatus respectively (total 6 rats), Same MRI parameters were used just as above. Iron particle density and cells was measured by HE and Prussian blue stain under microscopy. RESULTS: Different cell population was cultured with 0 microg/ml, 25 microg/ml, 50 microg/ml USPIO about 12 hours. The MR signal intensity of labeling cells were inversely correlated with the different concentration of USPIO groups in T(2)W and GRE/30 degrees imaging (t = 4.19, 3.38, P < 0.05) in vitro. There was an inversely correlation between the labeling cell population and the signal intensity at the same concentration of USPIO (t = 5.16, 2.35, 4.41; P < 0.05). Dyeing degree of labeling cells stained by Prussian blue gradually deepened from 25 microg/ml to 50 microg/ml by microscopy. In vivo MRI can clearly show the cells labeled with 25 microg/ml USPIO. CONCLUSIONS: Iron particle density in the rat glioma cells were gradually increased with the concentration of USPIO. The MR signal intensity was inversely correlated with the cell population at the same condition. 25 microg/ml USPIO labeling rat glioma cells were enough for in vivo monitoring by MRI.

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.

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.