Myocardial infarction size as an independent predictor of intramyocardial haemorrhage in acute reperfused myocardial ischaemic rats.

BACKGROUND: In previous studies, haemorrhage occurred only with large infarct sizes, and studies found a moderate correlation between the extent of necrosis and haemorrhage, but the extent of infarction size in these studies was limited. This study aimed to find the correlations between intramyocardial haemorrhage (IMH), myocardial infarction (MI), and myocardial oedema (ME) from small to large sizes of MI in a 7.0-T MR scanner. METHODS: Different sizes of myocardial infarction were induced by occluding different sections of the proximal left anterior descending coronary artery (1-3 mm under the left auricle). T2*-mapping, T2-mapping and late gadolinium enhancement (LGE) sequences were performed on a 7.0 T MR system at Days 2 and 7. T2*- and T2-maps were calculated using custom-made software. All areas were expressed as a percentage of the entire myocardial tissue of the left ventricle. The rats were divided into two groups based on the T2* results and pathological findings; MI with IMH was referred to as the + IMH group, while MI without IMH was referred to as the -IMH group. RESULTS: The final experimental sample consisted of 25 rats in the + IMH group and 10 rats in the -IMH group. For the + IMH group on Day 2, there was a significant positive correlation between IMH size and MI size (r = 0.677, P < 0.01) and a positive correlation between IMH size and ME size (r = 0.552, P < 0.01). On Day 7, there was a significant positive correlation between IMH size and MI size (r = 0.711, P < 0.01), while no correlation was found between IMH size and ME size (r = 0.429, P = 0.097). The MI sizes of the + IMH group were larger than those of the -IMH group (P < 0.01). CONCLUSIONS: Infarction size prior to reperfusion is a critical factor in determining IMH size in rats.

Low-dose dobutamine cardiovascular magnetic resonance segmental strain study of early phase of intramyocardial hemorrhage rats.

BACKGROUND: This study investigates the segmental myocardial strain of the early phase of intramyocardial hemorrhage (IMH) caused by reperfused myocardial infarction (MI) in rats by low-dose dobutamine (LDD) cardiovascular magnetic resonance (CMR) feature-tracking. METHODS: Nine sham rats and nine rats with 60-min myocardial ischemia followed by 48-h reperfusion were investigated using CMR, including T2*-mapping sequence and fast imaging with steady-state precession (FISP)-cine sequence. Another FISP-cine sequence was acquired after 2 min of dobutamine injection; the MI, IMH, and Non-MI (NMI) areas were identified. The values of peak radial strains (PRS) and peak circumferential strains (PCS) of the MI, IMH and NMI segments were acquired. The efficiency of PRS and PCS (EPRS and EPCS, respectively) were calculated on the basis of the time of every single heartbeat. RESULTS: The PRS, PCS, EPRS, and EPCS of the sham group increased after LDD injection. However, the PRS, PCS, EPRS, and EPCS of the IMH segment did not increase. Moreover, the PRS and PCS of the MI and NMI segments did not increase, but the EPRS and EPCS of these segments increased. The PRS, PCS, EPRS, and EPCS of the IMH segment were lower than those of the MI and NMI segments before and after LDD injection, but without a significant difference between MI segment and NMI segment before and after LDD injection. CONCLUSIONS: LDD could help assess dysfunctions in segments with IMH, especially using the efficiency of strain. IMH was a crucial factor that decreased segmental movement and reserved function.

[Tracking Early Reperfused Myocardial Infarction using Cardiac MR].

OBJECTIVE: To determine segmental myocardial changes in cardiovascular magnetic resonance feature-tracking (CMR-FT) in the early phase of reperfused myocardial infarction in patients and rats. METHODS: Ten patients receiving percutaneous coronary interventions (2-10 d) and 10 rats with 60 min induced myocardial ischemia followed by reperfusions (48 h and 7 d) were investigated by MRI. The steady state free precession cine and late gadolinium enhancement (LGE) sequences were measured to evaluate the standard short axis of the whole heart after an injection of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, Magnevist, Bayer Health Care Pharmaceuticals) at a dose of 0.1 mmol/kg. The infarction sizes (all areas were expressed as a percentage of the whole myocardial tissues of left ventricle (LV), end-diastolic volume (EDV) and ejection fractions (EF) were calculated. The MRI cine images were analyzed using the myocardial feature tracking software CVI, estimating the peak value of radial strains (RS) and circumferential strains (CS) of the 16 AHA segments excluding apex cordis. The complete myocardial infarction (CMI) segments, partial myocardial infarction (PMI) segments and non-myocardial infarction (NMI) segments were identified and compared. RESULTS: Patients: The radial strain and circumferential strain of the CMI and PMI segments were smaller than the NMI segment (both P < 0.01). However, there was no significant difference between the CMI and the PMI segment (P>0.05). Rats: No significance differences were found in EF and EDV between the two time period 48 h and 7 d (both P>0.05). The radial strain and circumferential strain of the CMI and PMI segments were smaller than the NMI segment (all P < 0.01). But there was no significance difference between the CMI segment and the PMI segment (P>0.05). No significant changes in the global radial strain and the circumferential strain were found over time (both P>0.05). But the segmental radial strain and circumferential strain became larger over time (all P < 0.05). CONCLUSIONS: The systolic ability of myocardium decreases as a result of reperfusion injury in the early phase of reperfused myocardial infarction. But it can gradually recover over time with reperfusion.

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.

Endogenous contrast T1rho cardiac magnetic resonance for myocardial fibrosis in hypertrophic cardiomyopathy patients.

BACKGROUND: Late gadolinium enhancement (LGE) is a standard method to evaluate myocardial fibrosis, but restricted due to contrast agent contraindications. Non-contrast T1rho can generate endogenous contrast, and detect fibrosis in chronic myocardial infarction. However, T1rho for hypertrophic cardiomyopathy (HCM) patients is still unreported. The present study aimed to investigate T1rho for fibrotic assessment and the clinical implication in HCM patients. METHODS: 18 HCM patients and 8 controls underwent T1rho, cine, and LGE cardiac magnetic resonance (CMR). T1rho relaxation time maps were created. Left ventricular (LV) parameters assessed included wall thickness, wall thickening, chamber volumes, ejection function, and fibrotic size. New York Heart Association (NYHA) functional classification was conducted. RESULTS: Hyper-T1rho value was identified in 12 HCM patients, consistent with LGE. The mean T1rho values of controls, LGE-negative patients, and remote myocardium of LGE-positive patients were 42.2±1.6ms, 43.9±2.5ms, and 42.5±1.2ms respectively, and these values showed no significant difference (all p>0.05). T1rho-3-SD and T1rho-4-SD fibrotic sizes (32.5±14.0% and 25.1±11.5%) did not differ from LGE fibrotic size (28.1±11.2%) (both p>0.05). For the fibrotic size, T1rho-3-SD method obtained the strongest correlation with LGE (r=0.88, p<0.001), and T1rho-4-SD obtained the minimal mean difference with LGE (-3.1%; -15.2 to 9.1%), compared with other SDs. All the fibrotic sizes assessed by both methods correlated directly with LV maximal end-diastolic thickness (all p<0.05). Negative correlation was found between T1rho-4-SD fibrotic size and LV ejection fraction (r=-0.49, p=0.11). T1rho-4-SD fibrotic size showed positive correlation with NYHA class (r=0.46, p=0.13). CONCLUSIONS: T1rho CMR has potential to detect fibrosis in HCM patients. 4-SD may be the appropriate threshold for assessment.

Establishment and ultrasound characteristics of atherosclerosis in rhesus monkey.

BACKGROUND: Atherosclerosis is one of the main risk factors cause acute cerebral-cardio vascular diseases. It's 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. METHODS: Fifty 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. RESULTS: Serum 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. CONCLUSIONS: After 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.

Assessment of myocardial edema and area at risk in a rat model of myocardial infarction with a faster T2 mapping method.

BACKGROUND: The common T2 mapping is not suitable for the use in rat heart with high heart rate, unless data are acquired in multiple cardiac cycles. PURPOSE: To evaluate a simplified T2 mapping method for faster assessment of myocardial edema and area at risk in a rat model of myocardial infarction. MATERIAL AND METHODS: The simplified T2 mapping method (TR/TE, 1500 ms/10, 20, 30 ms) was implemented at a 7.0T MRI system. The accuracy of T2 mapping was compared with a standard T2 mapping method (TR, 2500 ms, 16 TEs equally spaced from 11 ms to 176 ms) in thigh muscles in rats (n = 6) and a phantom. This method was further evaluated in normal rats (n = 8) and rats with myocardial infarction (n = 8). Late gadolinium enhancement images were also acquired in the rats with myocardial infarction. RESULTS: T2 values of simplified T2 mapping in the muscles and phantom were 27.3 ± 2 ms and 26.5 ± 1.1 ms, which were similar to the T2 values obtained by the standard T2 mapping method (28.1 ± 1.4 ms, P > 0.05; 26.9 ± 1.7 ms). No significant difference in T2 distribution (different segments and slices from base to apex) in the whole heart was found in normal rats (25.6 ± 3.3 ms, P > 0.05). The mean T2 value in the myocardial edema regions of myocardial infarction rats (37 ± 4.9 ms) was significantly higher than that of the normal rats (25.6 ± 3.3 ms, P < 0.001). The T2 value in the myocardial infarction core of myocardial infarction rats (39.9 ± 3.6 ms) was significantly higher than that of area at risk (34.7 ± 2.9 ms, P < 0.001). CONCLUSION: The simplified myocardial T2 mapping is technically feasible and accurate, and can readily detect myocardial edema and area at risk in rats with high heart rate.

In vivo dynamic monitoring of the biological behavior of labeled C6 glioma by MRI.

Gliomas are the most common type of intracranial tumor and have the highest rate of mortality. The aims of this study were to investigate the long-term course and biological behavior of orthotopically implanted C6 gliomas and to dynamically monitor the distribution of superparamagnetic iron oxide (SPIO) nanocomposite-labeled C6 glioma cells in rats using 7.0T MRI. We observed that in the MRI of the rats implanted with SPIO-labeled cells, there were pronounced hypointense signal bands, which faded over time, but remained visible up to day 27 after implantation. We observed that the first tumors were detected as early as 2 days after implantation, presenting as slightly hyperintense regions with indefinite boundaries in the T1-weighted images (T1WIs). On the 9th day, thick tumor feeder vessels, ~0.2 mm in diameter, were observed and these increased rapidly over time. Edema was observed in the labeled and unlabeled groups in the T2WIs. Both the central hypointense signal area and the peripheral cogwheel-shaped hypointense signal band in the tumor were observed on the post-contrast T1WIs, in accordance with the necrosis observed in the photomicrographs following hematoxylin and eosin (HE) staining. In conclusion, labeling tumor cells with SPIO and performing an MRI scan dynamically monitors the development and biological behavior of glioma at a very early stage.

Tracking tumor cells in lymphatics in a mice xenograft model by magnetic resonance imaging.

To enrich our understanding of the mechanism of tumor lymphatic metastasis, we developed a model system for tracking metastatic tumor cells in the lymphatic system with cellular magnetic resonance imaging (MRI) in live mice to observe the interaction between tumor cells and the lymphatic system. Nude mice were inoculated subcutaneously with superparamagnetic iron oxide (SPIO)-labeled and unlabeled LOVO cells in the foot pad, groin, or axillary area. Serial 7 T MRI of the tumors and surrounding regions was performed in the following 2 weeks. After imaging, tumor tissues and regional lymph nodes were collected and subjected to immunohistologic analysis. T2/T2*-weighted MRIs showed the primary tumor growth and the draining lymphatic architecture, as well as the SPIO-labeled tumor cells metastasized into the regional lymph node at 8 days. MRIs also revealed information on sentinel lymph node mapping with high-resolution anatomic information. Histologic findings confirmed the in vivo MRI results and revealed lymphangiogenesis, angiogenesis, infiltration of macrophages, and expression of vascular endothelial growth factor C in tumor and draining lymph nodes as well. This technology provides a powerful tool for tracking SPIO-labeled cancer cells in the lymphatics by cellular MRI. There was a close relationship between tumor lymphatic metastasis and lymphangiogenesis.