Characterization of kidneys in patients with systemic sclerosis by multi-parametric magnetic resonance quantitative imaging.

PURPOSE: To determine the usefulness of multiparametric magnetic resonance (MR) quantitative imaging in characterizing the kidneys in systemic sclerosis (SSc) patients. MATERIAL AND METHODS: Forty-six SSc patients (47.9 ± 12.8 years, 40 females) and 22 age- and sex- matched healthy volunteers (46.1 ± 13.8 years, 20 females) were recruited and underwent renal MR imaging by acquiring blood oxygen level dependent and saturated multi-delay renal arterial spin labeling (SAMURAI) sequences. The T2* value, T1 value, renal blood flow (RBF), arterial bolus arrival time (aBAT), and tissue bolus arrival time (tBAT) of renal cortex were measured and compared among diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) groups and healthy controls using One-way ANOVA and analyzed by logistic regression. RESULTS: Compared to healthy volunteers, SSc patients with normal estimated glomerular filtration rate (n = 40) had significantly lower T2* value (P = 0.026) in the left renal cortex, longer T1 value (right: P = 0.015; left: P = 0.023), lower RBF (right: P < 0.001; left: P < 0.001), and shorter tBAT (right: P < 0.001; left: P = 0.005) in both right and left renal cortex after adjusting for demographics. The dcSSc patients (n = 23) had significantly lower RBF in both right (226.7 ± 65.2 mL/100 g/min vs. 278.2 ± 73.5 mL/100 g/min, P = 0.022) and left (194.5 ± 71.5 mL/100 g/min vs. 252.7 ± 84.4 mL/100 g/min, P = 0.020) renal cortex compared to the lcSSc patients (n = 23) after adjusting for demographics, but the significance of the difference was attenuated after further adjusting for modified Rodnan skin score and digital ulcers. CONCLUSION: Multi-parametric MR quantitative imaging, particularly multi-delay ASL perfusion imaging, is a useful technique for characterizing the kidneys and classification of SSc patients.

Diffusing capacity of lungs for carbon monoxide associated with subclinical myocardial impairment in systemic sclerosis: A cardiac MR study.

BACKGROUND: Systemic sclerosis (SSc) is characterised by microvascular and fibrotic lesions, which are located not only in skin but also in lungs and heart. OBJECTIVE: This study aimed to investigate the association between lung function and myocardial T1 values using cardiac MR (CMR) imaging in patients with SSc without cardiovascular symptoms. METHODS: The SSc patients and age- and sex-matched healthy subjects underwent CMR. The cardiac function and native T1 values of myocardium and lung function were measured. Spearman's rank correlations and linear regression analyses were performed to determine the association between lung function and myocardial T1. RESULTS: Forty-five SSc patients (aged 47.7±13.2 years, 40 females) and 23 (aged 46.0±14.4 years, 20 females) healthy subjects were enrolled. SSc patients exhibited considerably higher native T1 values compared with healthy subjects (1305.9±49.8 ms vs 1272.6±37.6 ms, p=0.006). Linear regression analysis revealed that decrease of diffusing capacity of lungs for carbon monoxide (DLCO) in SSc patients was notably associated with myocardial native T1 value before (ß -1.017; 95% CI -1.883 to -0.151; p=0.022) and after adjusting for confounding factors (ß -1.108; 95% CI -2.053 to -0.164; p=0.023). Moderate-to-severe decrease of DLCO was found to be significantly associated with myocardial native T1 value (ß 48.006; 95% CI 17.822 to 78.190; p=0.003) after adjusting for confounding factors. CONCLUSION: DLCO inversely correlates with myocardial native T1 values in SSc patients, particularly moderate-to-severely decreased DLCO, suggesting that DLCO might be a potential indicator for subclinical myocardial impairment in SSc patients.

Characterization and Assessment of Projection Probability Density Function and Enhanced Sampling in Self-Collimation SPECT.

We have recently reported a self-collimation SPECT (SC-SPECT) design concept that constructs sensitive detectors in a multi-ring interspaced mosaic architecture to simultaneously improve system spatial resolution and sensitivity. In this work, through numerical and Monte-Carlo simulation studies, we investigate this new design concept by analyzing its projection probability density functions (PPDF) and the effects of enhanced sampling, i.e. having rotational and translational object movements during imaging. We first quantitatively characterize PPDFs by their widths and edge slopes. Then we compare the PPDFs of an SC-SPECT and a series of multiple-pinhole SPECT (MPH-SPECT) systems and assess the impact of PPDFs - combined with enhanced sampling - on image contrast recovery coefficient and variance through phantom studies. We show the PPDFs of SC- SPECT have steeper edges and a wider range of width, and these attributes enable SC-SPECT to achieve better performance.

Study of 99mTc absorption on micro-sized ion exchange resins to achieve high activity for SPECT.

In single-photon emission computed tomography (SPECT), a micro-sized 99mTc source is routinely used for performance measurement, geometry calibration, and system matrix generation. Therefore, a micro-sized source is critical in nuclear instrument production and quality control. Standard methods can only produce a point source with a large size and low total activity, as they are limited by the concentration of the 99mTc solution. The absorption of 99mTc on ion exchange resins has been used; however, few studies have quantitatively evaluated the absorption process and optimized the source activity. This paper proposes a procedure for producing a micro-sized 99mTc resin source with a super-high concentration, as well as a method for the fast measurement of the point source time-activity curve (TAC). Experiments on two resin point sources with diameters of 0.681 mm and 0.326 mm were carried out. Two semi-empirical models, including the first kinetic model and the pseudo-second-order rate equation model, were used to fit TACs. The results show the first kinetic model fit better, which suggests an acquisition time of 2-4 h is needed for optimization. The verification experiment demonstrates a resin point source with a diameter of 0.35 mm and total activity of 10.6 mCi (i.e., 59.1 Ci/mL concentration) was produced.

Likely Common Role of Hypoxia in Driving 18F-FDG Uptake in Cancer, Myocardial Ischemia, Inflammation and Infection.

First introduced in 1976, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has become an indispensable tool for diagnosis and prognostic evaluation of tumors, heart disease, as well as other conditions, including inflammation and infection. Because 18F-FDG can accurately reflect the glucose metabolism level of organs and tissues, it is known as a "century molecule" and is currently the main agent for PET imaging. The degree of 18F-FDG uptake by cells is related to both the rate of glucose metabolism and glucose transporter expression. These, in turn, are strongly influenced by hypoxia, in which cells meet their energy needs through glycolysis, and 18F-FDG uptake increased due to hypoxia. 18F-FDG uptake is a complex process, and hypoxia may be one of the fundamental driving forces. The correct interpretation of 18F-FDG uptake in PET imaging can help clinics make treatment decisions more accurately and effectively. In this article, we review the application of 18F-FDG PET in tumors, myocardium, and inflammation. We discuss the relationship between 18F-FDG uptake and hypoxia, the possible mechanism of 18F-FDG uptake caused by hypoxia, and the associated clinical implications.

Self-Collimating SPECT With Multi-Layer Interspaced Mosaic Detectors.

Conventional single photon emission computed tomography (SPECT) relies on mechanical collimation whose resolution and sensitivity are interdependent, the best performance a SPECT system can attain is only a compromise of these two equally desired properties. To simultaneously achieve high resolution and sensitivity, we propose to use sensitive detectors constructed in a multi-layer in ter spaced mosaicdetectors (MATRICES) architecture to accomplish part of the collimation needed. We name this new approach self-collimation. We evaluate three self-collimating SPECT systems and report their imaging performance: 1) A simulated human brain SPECT achieves 3.88% sensitivity, it clearly resolves 0.5-mm and 1.0-mm hot-rod patterns at noise-free and realistic count-levels, respectively; 2) a simulated mouse SPECT achieves 1.25% sensitivity, it clearly resolves 50- [Formula: see text] and 100- [Formula: see text] hot-rod patterns at noise-free and realistic count-levels, respectively; 3) a SPECT prototype achieves 0.14% sensitivity and clearly separates 0.3-mm-diameter point sources of which the center-to-center neighbor distance is also 0.3 mm. Simulated contrast phantom studies show excellent resolution and signal-to-noise performance. The unprecedented system performance demonstrated by these 3 SPECT scanners is a clear manifestation of the superiority of the self-collimating approach over conventional mechanical collimation. It represents a potential paradigm shift in SPECT technology development.

The Availability of the α7-Nicotinic Acetylcholine Receptor in Early Identification of Vulnerable Atherosclerotic Plaques: A Study Using a Novel 18F-Label Radioligand PET.

Background: It has been confirmed that the α7-nicotinic acetylcholine receptor (α7nAChR) is an important target for identifying vulnerable atherosclerotic plaques. Previously, we successfully designed and synthesized a series of 18F-labeled PET molecular probes targeting α7nAChR, which are mainly used in the diagnosis of Alzheimer's disease. Based on the characteristics of α7nAChR in blood vessels, we have firstly screened for a suitable novel 18F-labeled PET molecular probe ([18F]YLF-DW), with high selectivity for α7nAChR over α4ß2nAChR and a good effect for the imaging of atherosclerotic animal models, to effectively identify vulnerable atherosclerotic plaques at an early stage. Meanwhile, we compared it with the "gold standard" pathological examination of atherosclerosis, to verify the reliability of [18F]YLF-DW in early diagnosis of atherosclerosis. Methods: The vulnerable atherosclerotic plaques model of ApoE-/-mice were successfully established. Then based on the methods of 3D-QSAR and molecular docking, we designed oxazolo[4,5-b] pyridines and fluorenone compounds, which are targeted at α7nAChR. Through further screening, a novel alpha7 nicotinic acetylcholine receptor radioligand ([18F]YLF-DW) was synthesized and automatically 18F-labeled using a Stynthra RNplus module. Subsequently, we employed [18F]YLF-DW for the targeting of α7nAChR in atherosclerotic plaques and control group, using a micro-PET/CT respectively. After imaging, the mice were sacrificed by air embolism and the carotid arteries taken out for making circular sections. The paraffin embedded specimens were sectioned with 5 µm thickness and stained with oil red. After staining, immunohistochemistry experiment was carried out to verify the effect of micro-PET/CT imaging. Results: The micro-PET/CT imaging successfully identified the vulnerable atherosclerotic plaques in the carotid arteries of ApoE-/-mice; whereas, no signal was observed in normal control mice. In addition, compared with the traditional imaging agent [18F]FDG, [18F]YLF-DW had a significant effect on the early plaques imaging of carotid atherosclerosis. The results of oil red staining and immunohistochemistry also showed early formations of carotid plaques in ApoE-/-mice and provided pathological bases for the evaluation of imaging effect. Conclusion: We innovated to apply the novel molecular probe ([18F]YLF-DW) to the identification of vulnerable atherosclerotic plaques in carotid arteries, to detect atherosclerosis early inflammatory response and provide powerful input for the early diagnosis of atherosclerotic lesions, which may play an early warning role in cardiovascular acute events.

Rescue Protocol to Improve the Image Quality of 18F-FDG PET/CT Myocardial Metabolic Imaging.

PURPOSE: 18F-FDG PET myocardial metabolic imaging is used to estimate myocardial viability. However, poor image quality can affect the accurate quantification of viable myocardium. We assessed the feasibility of a rescue protocol that reinjected low-dose 18F-FDG with simultaneous 1 to 2 U of insulin injection and oral administration of 10 g of glucose to improve the image quality of 18F-FDG PET myocardial metabolic imaging. PATIENTS AND METHODS: Fifty-one consecutive patients with poor quality to uninterpretable 18F-FDG PET/CT myocardial metabolic images received the rescue protocol immediately after the initial image acquisition. The postrescue image acquisition was performed 1 hour later. The rescue image quality was compared with the initial image. The qualitative visual estimation of the images was graded as follows: grade 0, homogeneous, minimal uptake; grade 1, predominantly minimal or mild uptake; grade 2, moderate uptake; and grade 3, good uptake. The myocardium-to-blood pool activity ratio (M/B) was measured to assess the image quality quantitatively. RESULTS: The grades of 0 to 3 were observed in 24 (47%), 27 (53%), 0 (0%), and 0 (0%) patients, respectively, for the initial imaging, and in 0 (0%), 3 (5.9%), 4 (7.8%), and 44 (86.3%) patients for the rescue imaging (P < 0.001). The rescue M/B was significantly higher than the initial M/B (3.4 ± 1.4 vs 1.6 ± 0.6, respectively; P < 0.001). CONCLUSIONS: The rescue protocol successfully and rapidly improved the quality of myocardial 18F-FDG metabolic imaging.

Evaluation of left ventricular volumes and ejection fraction by 99mTc-MIBI gated SPECT and 18F-FDG gated PET in patients with prior myocardial infarction.

BACKGROUND: This study aimed to compare the accuracy of gated-SPECT (GSPECT) and gated-PET (GPET) in the assessment of left ventricular (LV) end-diastolic volumes (EDVs), end-systolic volumes (ESVs) and LV ejection fractions (LVEFs) among patients with prior myocardial infarction (MI). METHODS: One hundred and sixty-eight consecutive patients with MI who underwent GSPECT and GPET were included. Of them, 76 patients underwent CMR in addition to the two imaging modalities. The measurements of LV volumes and LVEF were performed using Quantitative Gated SPECT (QGS), Emory Cardiac Toolbox (ECTB), and 4D-MSPECT (4DM). RESULTS: The correlation between GPET, GSPECT, and CMR were excellent for LV EDV (r = 0.855 to 0.914), ESV (r = 0.852 to 0.949), and LVEF (r = 0.618 to 0.820), as calculated from QGS, ECTB, and 4DM. In addition, subgroup analysis revealed that EDV, ESV, and LVEF measured by GPET were accurate in patients with different extents of total perfusion defect (TPD), viable myocardium, and perfusion/metabolic mismatch. Furthermore, multivariate regression analysis identified that mismatch score was associated with the difference in EDV (P < 0.05) measurements between GPET and CMR. CONCLUSIONS: In patients with MI, LV volumes and LVEF scores measured by both GSPECT and GPET imaging were comparable to those determined by CMR, but should not be interchangeable in individual patients.

Preserved myocardial viability in patients with chronic total occlusion of a single coronary artery.

OBJECTIVE: To assess the benefits of coronary collateral circulation on myocardial perfusion, viability and function in patients with total occlusion of a single coronary artery using the 99mTc-sestamibi SPECT and 18F-fluorodeoxyglucose PET. METHODS: 164 Consecutive patients were included who underwent coronary angiography results exhibited total occlusion of a single coronary artery and received 99mTc-MIBI SPECT and 18F-FDG PET within 90 days of angiography. Myocardial perfusion and viability in patients with collateral circulation and those without it were compared. Long-term follow-up was performed through a review of patient clinical records. RESULTS: Collateral circulation was present in 56 patients (34%) and absent in 108 patients (66%). The total perfusion defect size in patients with collateral circulation decreased when compared to those without (30% ± 13% to 35% ± 14%, P < .05). The myocardial viability was 22% ± 12% in patients with collateral circulation, and 12% ± 9% in those without (P < .001). The left ventricular ejection fraction was higher, and the end-diastolic and end-systolic left ventricular volumes were lower in patients with collateral circulation (39% ± 11%, 138 ± 66, 89 ± 57) compared to patients without collateral circulation (31% ± 9%, 177 ± 55, 125 ± 48, all P < .001, respectively). Multi-factor logistic regression identified that concerning the variables of sex, age, viable myocardium, collateral circulation, treatment type and others, only treatment type was significantly associated with therapeutic effects (OR 3.872, 95% CI 1.915-7.830, P < .001). CONCLUSION: Collateral circulation can preserve resting myocardial blood perfusion and myocardial viability, and help maintain the function of the left ventricular myocardium. The appropriate treatment strategy will have a substantial impact on the therapeutic outcome.

Correction to: IGF-1C domain-modified hydrogel enhanced the efficacy of stem cells in the treatment of AMI.

An amendment to this paper has been published and can be accessed via the original article.

IGF-1C domain-modified hydrogel enhanced the efficacy of stem cells in the treatment of AMI.

BACKGROUND: Due to the low survival rate of cell transplantation, stem cell has not been widely used in clinical treatment of acute myocardial infarction (AMI). In this study, we immobilized the C domain peptide of insulin-like growth factor-1 on chitosan (CS-IGF-1C) to obtain bioactive hydrogel. The purpose was to investigate whether CS-IGF-1C hydrogel incorporated with human placenta-derived mesenchymal stem cells (hP-MSCs) can boost the survival of hP-MSCs and enhance their therapeutic effects. METHODS: hP-MSCs, which continuously expressed green fluorescent protein (GFP) and firefly luciferase (Fluc), were transplanted with CS-IGF-1C hydrogel into a mouse myocardial infarction model. Cell survival was detected by bioluminescence imaging (BLI), and cardiac function was measured by echocardiogram. Real-time PCR and histological analysis were used to explore the therapeutic mechanism of CS-IGF-1C hydrogel. RESULTS: CS-IGF-1C hydrogel could induce the proliferation of hP-MSCs and exert anti-apoptotic effects in vitro. The Calcine-AM/PI staining results showed that hP-MSCs seeded on CS-IGF-1C hydrogel could protect neonatal mouse ventricular cardiomyocytes (NMVCs) against oxidative stress. It was observed by BLI that CS-IGF-1C hydrogel injected into ischemic myocardium could improve the survival rate of hP-MSCs. Histology analysis indicated that co-transplantation of the CS-IGF-1C hydrogel and hP-MSCs could increase angiogenesis, reduce collagen deposition, ameliorate left ventricular expanded, and further promote the recovery of cardiac function. Besides, we found that the inflammatory response was inhibited and the expression of apoptosis-related genes was downregulated by CS-IGF-1C hydrogel. CONCLUSIONS: CS-IGF-1C hydrogel provides a conducive microenvironment for cells and significantly boosts the survival of hP-MSCs in mouse myocardial infarction model, which suggest that it may be a potential candidate for prolonging the therapeutic effect of hP-MSCs during AMI.

IGF-1C domain-modified hydrogel enhances therapeutic potential of mesenchymal stem cells for hindlimb ischemia.

BACKGROUND: Poor cell engraftment and survival after transplantation limited the application of stem cell therapy. Synthetic biomaterials could provide an artificial microenvironment for stem cells, thereby improve cell survival and enhance the therapeutic efficiency of stem cells. METHODS: We synthesized a hydrogel by conjugating C domain peptide of insulin-like growth factor-1 (IGF-1C) onto chitosan (CS-IGF-1C hydrogel). Human placenta-derived mesenchymal stem cells (hP-MSCs), which constitutively express a red fluorescent protein (RFP) and renilla luciferase (Rluc), were co-transplanted with CS-IGF-1C hydrogel into a murine hindlimb ischemia model. Transgenic mice expressing firefly luciferase (Fluc) under the promoter of vascular endothelial growth factor receptor 2 (VEGFR2-Luc) were used. Dual bioluminescence imaging (BLI) was applied for tracking the survival of hP-MSCs by Rluc imaging and the VEGFR2 signal pathway activation by Fluc imaging. To investigate the therapeutic mechanism of CS-IGF-1C hydrogel, angiographic, real-time PCR, and histological analysis were carried out. RESULTS: CS-IGF-1C hydrogel could improve hP-MSCs survival as well as promote angiogenesis as confirmed by dual BLI. These results were consistent with accelerated skeletal muscle structural and functional recovery. Histology analysis confirmed that CS-IGF-1C hydrogel robustly prevented fibrosis as shown by reduced collagen deposition, along with increased angiogenesis. In addition, the protective effects of CS-IGF-1C hydrogel, such as inhibiting H2O2-induced apoptosis and reducing inflammatory responses, were proved by in vitro experiments. CONCLUSIONS: Taken together, IGF-1Cs provides a conducive niche for hP-MSCs to exert pro-mitogenic, anti-apoptotic, and pro-angiogenic effects, as well as to inhibit fibrosis. Thus, the incorporation of functional peptide into bioscaffolds represents a safe and feasible approach to augment the therapeutic efficacy of stem cells.

Relationship of myocardial hibernation, scar, and angiographic collateral flow in ischemic cardiomyopathy with coronary chronic total occlusion.

BACKGROUND: The relationship between myocardial viability and angiographic collateral flow is not fully elucidated in ischemic cardiomyopathy (ICM) with coronary artery chronic total occlusion (CTO). We aimed to clarify the relationship between myocardial hibernation, myocardial scar, and angiographic collateral flow in these patients. METHODS AND RESULTS: Seventy-one consecutive ICM patients with 122 CTOs and 652 dysfunctional segments within CTO territories were retrospectively analyzed. Myocardial hibernation (perfusion-metabolism mismatch) and the extent of 18F-fluorodeoxyglucose (FDG) abnormalities were assessed using 99mTc-sestamibi and 18F-FDG imaging. Myocardial scar was evaluated by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. Collateral flow observed on coronary angiography was assessed using Rentrop classification. In these patients, neither the extent nor frequency of myocardial hibernation or scar was related to the status of collateral flow. Moreover, the matching rate in determining myocardial viability was poor between any 2 imaging indices. The extent of 18F-FDG abnormalities was linearly related to the extent of LGE rather than myocardial hibernation. Of note, nearly one-third (30.4%) of segments with transmural scar still had hibernating tissue. Hibernation and non-transmural scar had higher sensitivity (63.0% and 66.7%) than collateral flow (37.0%) in predicting global functional improvement. CONCLUSIONS: Angiographic collateral cannot accurately predict myocardial viability, and has lower sensitivity in prediction of functional improvement in CTO territories in ICM patients. Hence, assessment of myocardial viability with non-invasive imaging modalities is of importance. Moreover, due to the lack of correlation between myocardial hibernation and scar, these two indices are complementary but not interchangeable.

Prostaglandin E2 hydrogel improves cutaneous wound healing via M2 macrophages polarization.

Wound healing is regulated by a complex series of events and overlapping phases. A delicate balance of cytokines and mediators in tissue repair is required for optimal therapy in clinical applications. Molecular imaging technologies, with their versatility in monitoring cellular and molecular events in living organisms, offer tangible options to better guide tissue repair by regulating the balance of cytokines and mediators at injured sites. Methods: A murine cutaneous wound healing model was developed to investigate if incorporation of prostaglandin E2 (PGE2) into chitosan (CS) hydrogel (CS+PGE2 hydrogel) could enhance its therapeutic effects. Bioluminescence imaging (BLI) was used to noninvasively monitor the inflammation and angiogenesis processes at injured sites during wound healing. We also investigated the M1 and M2 paradigm of macrophage activation during wound healing. Results: CS hydrogel could prolong the release of PGE2, thereby improving its tissue repair and regeneration capabilities. Molecular imaging results showed that the prolonged release of PGE2 could ameliorate inflammation by promoting the M2 phenotypic transformation of macrophages. Also, CS+PGE2 hydrogel could augment angiogenesis at the injured sites during the early phase of tissue repair, as revealed by BLI. Furthermore, our results demonstrated that CS+PGE2 hydrogel could regulate the balance among the three overlapping phases-inflammation, regeneration (angiogenesis), and remodeling (fibrosis)-during cutaneous wound healing. Conclusion: Our findings highlight the potential of the CS+PGE2 hydrogel as a novel therapeutic strategy for promoting tissue regeneration via M2 macrophage polarization. Moreover, molecular imaging provides a platform for monitoring cellular and molecular events in real-time during tissue repair and facilitates the discovery of optimal therapeutics for injury repair by regulating the balance of cytokines and mediators at injured sites.

Nitric oxide releasing hydrogel promotes endothelial differentiation of mouse embryonic stem cells.

Transplantation of endothelial cells (ECs) holds great promise for treating various kinds of ischemic diseases. However, the major challenge in ECs-based therapy in clinical applications is to provide high quality and enough amounts of cells. In this study, we developed a simple and efficient system to direct endothelial differentiation of mouse embryonic stem cells (ESCs) using a controllable chitosan nitric oxide (NO)-releasing hydrogel (CS-NO). ESCs were plated onto the hydrogel culture system, and the expressions of differentiation markers were measured. We found that the expression of Flk-1 (early ECs marker) and VE-cadherin (mature ECs marker) increased obviously under the controlled NO releasing environment. Moreover, the Flk-1 upregulation was accompanied by the activation of the phospho-inositide-3 kinase (PI3K)/Akt signaling. We also found that in the presence of the PI3K inhibitor (LY294002), the endothelial commitment of ESCs was abolished, indicating the importance of Akt phosphorylation in the endothelial differentiation of ESCs. Interestingly, in the absence of NO, the activation of Akt phosphorylation alone by using AKT activator (SC-79) did not profoundly promote the endothelial differentiation of ESCs, suggesting an interdependent relationship between NO and the Akt phosphorylation in driving endothelial fate specification of ESCs. Taken together, we demonstrated that NO releasing in a continuous and controlled manner is a simple and efficient method for directing the endothelial differentiation of ESCs without adding growth factors. STATEMENT OF SIGNIFICANCE: Fascinating data continues to show that artificial stem cell niche not only serve as a physical supporting scaffold for stem cells proliferation, but also as a novel platform for directing stem cell differentiation. Because of the lack of proper microenvironment for generating therapeutic endothelial cells (ECs) in vitro, the source of ECs for transplantation is the major limitation in ECs-based therapy to clinical applications. The current study established a feeder cell-free, 2-dimensional culture system for promoting the differentiation processes of embryonic stem cells (ESCs) committed to the endothelial lineage via using a nitric oxide (NO) controlled releasing hydrogel (CS-NO). Notably, the NO releasing from the hydrogel could selectively up-regulate Flk-1 (early ECs marker) and VE-cadherin (mature ECs marker) in the absence of growth factors, which was of crucial importance in the endothelial differentiation of ESCs. In summary, the current study proposes a simple and efficient method for directing the endothelial differentiation of ESCs without extra growth factors.

Dual-time-point myocardial 18F-FDG imaging in the detection of coronary artery disease.

BACKGROUND: Myocardial 18F-deoxyglucose (18F-FDG) uptake has been observed to be enhanced in patients with coronary artery disease (CAD) under fasting conditions. However, whether the increased 18F-FDG is induced by myocardial ischemia and how to discriminate ischemic from physiological 18F-FDG uptake have rarely been investigated. METHODS: Under fasting conditions, 18F-FDG PET imaging was performed in 52 patients with suspected CAD. Two 18F-FDG imaging sessions were conducted within two hours after a single administration of 18F-FDG (dual-time-point imaging), and with an intervention of an exercise test after the first imaging. Abnormal 18F-FDG uptake was determined by the classification of the 18F-FDG distribution pattern, and the changes of the 18F-FDG distribution between the two PET imaging sessions were analyzed. 99mTc-sestamibi was injected at peak exercise and myocardial perfusion imaging (MPI) was conducted after 18F-FDG imaging. Coronary angiography was considered the reference for diagnosing CAD. RESULTS: Overall, 54.8% (17/31) of CAD patients and 36.2% (21/58) of stenotic coronaries showed exercise-induced abnormal uptake of 18F-FDG. Based on the classification of the 18F-FDG distribution pattern, the sensitivity and specificity of exercise 18F-FDG imaging to diagnose CAD was 80.6% and 95.2% by patient analysis, 56.9% and 98.0% by vascular analysis, respectively. Compared with MPI, 18F-FDG imaging had a tendency to have higher sensitivity (80.6% vs 64.5%, P = 0.06) on the patient level. CONCLUSION: Myocardial ischemia can induce 18F-FDG uptake. With the classification of the 18F-FDG distribution pattern, dual-time-point 18F-FDG imaging under fasting conditions is efficient in diagnosing CAD.