Jiayu Sun

Manganese ferrite nanoparticle micellar nanocomposites as MRI contrast agent for liver imaging

Iron oxide nanoparticles are effective contrast agents for enhancement of magnetic resonance imaging at tissue, cellular or even molecular levels. In this study, manganese doped superparamagnetic iron oxide (Mn-SPIO) nanoparticles were used to form ultrasensitive MRI contrast agents for liver imaging. Hydrophobic Mn-SPIO nanoparticles are synthesized in organic phase and then transferred into water with the help of block copolymer mPEG-b-PCL. These Mn-SPIO nanoparticles are self-assembled into small clusters (mean diameter approximately 80nm) inside micelles as revealed by transmission electron microscopy. Mn-SPIO nanoparticles inside micelles decrease PCL crystallization temperatures, as verified from differential scanning calorimetry and Fourier transform infrared spectroscopy. The Mn-SPIO based nanocomposites are superparamagnetic at room temperature. At the magnetic field of 1.5T, Mn-SPIO nanoparticle clustering micelles have a T(2) relaxivity of 270 (Mn+Fe)mM(-1)s(-1), which is much higher than single Mn-SPIO nanoparticle containing lipid-PEG micelles. This clustered nanocomposite has brought significant liver contrast with signal intensity changes of -80% at 5min after intravenous administration. The time window for enhanced-MRI can last about 36h with obvious contrast on liver images. This sensitive MRI contrast agent may find applications in identification of small liver lesions, evaluation of the degree of liver cirrhosis, and differential diagnosis of other liver diseases.

Establishment and ultrasound characteristics of atherosclerosis in rhesus monkey

BackgroundAtherosclerosis is one of the main risk factors cause acute cerebral-cardio vascular diseases. Its of great significance to establish an atherosclerosis animal model that can mimic the characteristics and nature course of human patients. Therefore, a rhesus monkey model was induced by high-fat diet to monitor their lipid profile and intima-media thickness (IMT) of artery walls and study atherosclerosis progression.MethodsFifty male rhesus monkeys were enrolled in this study. All of these monkeys were aged 7 to 14 years with BMI >30 kg/m2. They were fed with high-fat diet containing 10% of fat for the first 48 weeks. Use ultrasound to measure the IMT at bilateral common carotid arteries and their bifurcations and aorta (AO) of the monkeys, and screen out the individuals with thickened IMT for the next phase. In the next 48 weeks, some of these monkeys (n = 4) were fed with standard diet containing 3% fat. Meanwhile the other monkeys (n = 5) were fed with high-fat diet for another 48 weeks. Their serum lipid level was monitored and arterial IMT was also determined periodically.ResultsSerum lipid level of all 50 monkeys elevated after fed with high-fat diet for the first 48 weeks. IMT thickening at right common carotid bifurcation and aorta (AO) was thickened in 9 monkeys. Furthermore, 4 of these 9 monkeys were fed with standard diet and other 5 monkeys were fed with high-fat diet in the following 48 weeks. The serum lipid level of the 4 monkeys recovered and their IMT at RBIF and AO did not progress. However, the lipid level of other 5 monkeys remained high, and their IMT thickening of AO progressed, and plaques and calcification focuses were found at the anterior wall of aorta near the bifurcation of common iliac artery.ConclusionsAfter high-fat diet induction for 96 weeks, serum lipid levels of rhesus monkeys elevated significantly, which subsequently caused IMT thickening and plaques formation. When IMT thickening occurred, further vascular injury may be prevented by reducing diet fat content. Our study indicates that vascular injury of high-fat diet induced rhesus monkey is similar to that of human in position and progression.

The quantification of blood-brain barrier disruption using dynamic contrast-enhanced magnetic resonance imaging in aging rhesus monkeys with spontaneous type 2 diabetes mellitus.

Microvascular lesions of the body are one of the most serious complications that can affect patients with type 2 diabetes mellitus. The blood-brain barrier (BBB) is a highly selective permeable barrier around the microvessels of the brain. This study investigated BBB disruption in diabetic rhesus monkeys using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Multi-slice DCE-MRI was used to quantify BBB permeability. Five diabetic monkeys and six control monkeys underwent magnetic resonance brain imaging in 3 Tesla MRI system. Regions of the frontal cortex, the temporal cortex, the basal ganglia, the thalamus, and the hippocampus in the two groups were selected as regions of interest to calculate the value of the transport coefficient Ktrans using the extended Tofts model. Permeability in the diabetic monkeys was significantly increased as compared with permeability in the normal control monkeys. Histopathologically, zonula occludens protein-1 decreased, immunoglobulin G leaked out of the blood, and nuclear factor E2-related factor translocated from the cytoplasm to the nuclei. It is likely that diabetes contributed to the increased BBB permeability.

Distribution pattern of left-ventricular myocardial strain analyzed by a cine MRI based deformation registration algorithm in healthy Chinese volunteers

The cine magnetic resonance imaging based technique feature tracking-cardiac magnetic resonance (FT-CMR) is emerging as a novel, simple and robust method to evaluate myocardial strain. We investigated the distribution characteristics of left-ventricular myocardial strain using a novel cine MRI based deformation registration algorithm (DRA) in a cohort of healthy Chinese subjects. A total of 130 healthy Chinese subjects were enrolled. Three components of orthogonal strain (radial, circumferential, longitudinal) of the left ventricle were analyzed using DRA on steady-state free precession cine sequence images. A distinct transmural circumferential strain gradient was observed in the left ventricle that showed universal increment from the epicardial to endocardial myocardial wall (epiwall: −15.4 ± 1.9%; midwall: −18.8 ± 2.0%; endowall: −22.3 ± 2.3%, P < 0.001). Longitudinal strain showed a similar trend from epicardial to endocardial layers (epiwall: −16.0 ± 2.9%; midwall: −15.6 ± 2.7%; endowall: −14.8 ± 2.4%, P < 0.001), but radial strain had a very heterogeneous distribution and variation. In the longitudinal direction from the base to the apex of the left ventricle, there was a trend of decreasing peak systolic longitudinal strain (basal: −23.3 ± 4.6%; mid: −13.7 ± 7.3%; apical: −13.2 ± 5.5%; P < 0.001). In conclusion, there are distinct distribution patterns of circumferential and longitudinal strain within the left ventricle in healthy Chinese subjects. These distribution patterns of strain may provide unique profiles for further study in different types of myocardial disease.

Preclinical evaluation of a urokinase plasminogen activator receptor-targeted nanoprobe in rhesus monkeys

Purpose To translate a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO) nanoparticles (uPAR-targeted human ATF-IONPs) into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys. Methods We assessed the changes in the following: magnetic resonance imaging (MRI) signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP) or without a PEG (ATF-IONP) coating. Results The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells, white blood cells, hemoglobin level, and platelets remained normal during the 3 months of the study. Conclusion All of the results suggest that a transient injury in terms of normal organ functions, but no microscopic necrotic lesions, was observed at a systemic delivery dose of 5 mg/kg of iron equivalent concentration in the acute phase, and that no chronic toxicity was found 3 months after the injection. Therefore, we conclude that uPAR-targeted IONPs have the potential to be used as receptor-targeted MRI contrasts as well as theranostic agents for the detection and treatment of human cancers in future studies.

Reference values of cardiac ventricular structure and function by steady‐state free‐procession MRI at 3.0T in healthy adult chinese volunteers

To establish normal reference values of left ventricular (LV) and right ventricular (RV) dimension, volume, mass, and ejection fraction in a Chinese population using cardiac magnetic resonance imaging (MRI).

Left Ventricular Myocardial Deformation on Cine MR Images: Relationship to Severity of Disease and Prognosis in Amyloid Light-Chain Amyloidosis.

Purpose To measure left ventricular (LV) myocardial strain with cine magnetic resonance (MR) imaging and a deformable registration algorithm (DRA) and to assess the prognostic value of myocardial strain in patients with light-chain (AL) amyloidosis. Materials and Methods In this prospective study, 78 consecutive patients with AL amyloidosis who underwent contrast material-enhanced cardiac MR imaging were enrolled at West China Hospital. LV myocardial strains and late gadolinium enhancement (LGE) were evaluated. Association between myocardial strain and all-cause mortality was analyzed with the stepwise Cox regression model. Results Global longitudinal strain (GLS) and global circumferential strain (GCS) were significantly lower in the no or nonspecific LGE group compared with the subendocardial LGE and transmural LGE groups (mean GLS, -10% ± 3 [standard deviation] vs -7% ± 3 vs -4% ± 1; P < .001) (mean GCS, -13% ± 3 vs -11% ± 3 vs -7% ± 2; P < .001). GLS and GCS were reduced in patients without clinical cardiac amyloidosis (mean GLS, -13% ± 3 vs -16% ± 2; P = .005) (mean GCS, -16% ± 1 vs -19% ± 2; P = .02). Circumferential and radial strains were impaired in basal segments in accordance with the distribution of LGE. Multivariate Cox analysis revealed that GCS (hazard ratio [HR] = 1.16 per 1% absolute decrease; 95% confidence interval [CI]: 1.03, 1.31; P = .02) and the presence of transmural LGE (HR = 1.75; 95% CI: 1.10, 2.80; P = .02) were independent predictors of all-cause mortality after adjustment for LV ejection fraction, right ventricular ejection fraction, LV mass index, GLS, and global radial strain. Conclusion Strain parameters derived with cine MR imaging-based DRA may be a new noninvasive imaging marker with which to evaluate the extent of cardiac amyloid infiltration and may offer independent prognostic information for all-cause mortality in patients with AL amyloidosis.

Improved segmental myocardial strain reproducibility using deformable registration algorithms compared with feature tracking cardiac MRI and speckle tracking echocardiography: Segmental Myocardial Strain Using DRA

Segmental myocardial strain using feature tracking (FT) cardiac MRI is not acceptable due to poor reproducibility.

Early detection of myocardial involvement by T1 mapping of cardiac MRI in idiopathic inflammatory myopathy: T1 Mapping of Cardiac MRI in IIM

Polymyositis (PM) and dermatomyositis (DM) are common types of idiopathic inflammatory myopathy (IIM), wherein patients are prone to adverse cardiovascular events.

Age and Gender Impact the Measurement of Myocardial Interstitial Fibrosis in a Healthy Adult Chinese Population: A Cardiac Magnetic Resonance Study

Background: Diffuse myocardial fibrosis is a common pathological process in many cardiovascular diseases. In order to determine disease, we must have standard normal imaging values. We investigated myocardial interstitial fibrosis of the left ventricle (LV) in a healthy population of Chinese adults and explored the impact of gender, age, and other physiological factors using a T1 mapping technique of cardiac magnetic resonance imaging (CMR). Materials and Methods: We recruited 69 healthy adult Chinese subjects (35 males; age 18–76). LV function and global strain were obtained from functional imaging. T1 mapping was performed using a modified look-locker sequence. Global and segmental native T1 and extracellular volume (ECV) were calculated using dedicated software. Gender, age, and segmental variation of both native myocardial T1 and ECV of the LV were analyzed. Results: The global myocardial native T1 and ECV of the LV in this Chinese adult healthy population was 1,202 ± 45 ms and 27 ± 3% at 3T field strength, respectively. Females had a higher myocardial native T1 and ECV of the LV compared to males [1,210 (1,188–1,264) ms vs. 1,182 (1,150–1,211) ms, P < 0.001; 28 ± 3 vs. 26 ± 3%, P = 0.027, respectively]. ECV in older group was higher than younger group [27 (26–29)% vs. 25 (24–29), P = 0.019]. The multi-variate linear regression analysis showed that only gender (Beta = −0.512, P < 0.001) was independently related with global native T1 of LV while gender (Beta = −0.278, P = 0.017) and age (Beta = 0.303, P = 0.010) were independently related with global ECV of LV. From the base to apex of the LV, myocardial native T1 (P = 0.020) and ECV (P < 0.001) significantly increased. Within the same slice of the LV, there were significant segmental variations of both myocardial native T1 (P < 0.001) and ECV (P < 0.001) values. Conclusion: Gender and age have significant impacts on the imaging markers of myocardial interstitial fibrosis in healthy adult Chinese volunteers. Segmental variation of myocardial interstitial fibrosis was also observed.