Arterial Spin Labeling Magnetic Resonance Imaging in Healthy Adults: Mathematical Model Fitting to Assess Age-Related Perfusion Pattern

Objective@#To investigate the age-dependent changes in regional cerebral blood flow (CBF) in healthy adults by fitting mathematical models to imaging data. @*Materials and Methods@#In this prospective study, 90 healthy adults underwent pseudo-continuous arterial spin labeling imaging of the brain. Regional CBF values were extracted from the arterial spin labeling images of each subject. Multivariable regression with the Akaike information criterion, link test, and F test (Ramsey’s regression equation specification error test) was performed for 7 models in every brain region to determine the best mathematical model for fitting the relationship between CBF and age. @*Results@#Of all 87 brain regions, 68 brain regions were best fitted by cubic models, 9 brain regions were best fitted by quadratic models, and 10 brain regions were best fitted by linear models. In most brain regions (global gray matter and the other 65 brain regions), CBF decreased nonlinearly with aging, and the rate of CBF reduction decreased with aging, gradually approaching 0 after approximately 60. CBF in some regions of the frontal, parietal, and occipital lobes increased nonlinearly with aging before age 30, approximately, and decreased nonlinearly with aging for the rest of life. @*Conclusion@#In adults, the age-related perfusion patterns in most brain regions were best fitted by the cubic models, and age-dependent CBF changes were nonlinear.

Arterial Spin Labeling Magnetic Resonance Imaging in Healthy Adults: Mathematical Model Fitting to Assess Age-Related Perfusion Pattern

Objective@#To investigate the age-dependent changes in regional cerebral blood flow (CBF) in healthy adults by fitting mathematical models to imaging data. @*Materials and Methods@#In this prospective study, 90 healthy adults underwent pseudo-continuous arterial spin labeling imaging of the brain. Regional CBF values were extracted from the arterial spin labeling images of each subject. Multivariable regression with the Akaike information criterion, link test, and F test (Ramsey’s regression equation specification error test) was performed for 7 models in every brain region to determine the best mathematical model for fitting the relationship between CBF and age. @*Results@#Of all 87 brain regions, 68 brain regions were best fitted by cubic models, 9 brain regions were best fitted by quadratic models, and 10 brain regions were best fitted by linear models. In most brain regions (global gray matter and the other 65 brain regions), CBF decreased nonlinearly with aging, and the rate of CBF reduction decreased with aging, gradually approaching 0 after approximately 60. CBF in some regions of the frontal, parietal, and occipital lobes increased nonlinearly with aging before age 30, approximately, and decreased nonlinearly with aging for the rest of life. @*Conclusion@#In adults, the age-related perfusion patterns in most brain regions were best fitted by the cubic models, and age-dependent CBF changes were nonlinear.

Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury and Preserves Left Ventricular Systolic Function in Rats, as Evaluated by 7T Cardiovascular Magnetic Resonance Imaging

Objective@#The occurrence of intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO) in myocardial infarction (MI), known as severe ischemia/reperfusion injury (IRI), has been associated with adverse remodeling. APT102, a soluble human recombinant ecto-nucleoside triphosphate diphosphohydrolase-1, can hydrolyze extracellular nucleotides to attenuate their prothrombotic and proinflammatory effects. The purpose of this study was to temporally evaluate the therapeutic effect of APT102 on IRI in rats and to elucidate the evolution of IRI in the acute stage using cardiovascular magnetic resonance imaging (CMRI). @*Materials and Methods@#Fifty-four rats with MI, induced by ligation of the origin of the left anterior descending coronary artery for 60 minutes, were randomly divided into the APT102 (n = 27) or control (n = 27) group. Intravenous infusion of APT102 (0.3 mg/kg) or placebo was administered 15 minutes before reperfusion, and then 24 hours, 48 hours, 72 hours, and on day 4 after reperfusion. CMRI was performed at 24 hours, 48 hours, 72 hours, and on day 5 post-reperfusion using a 7T system and the hearts were collected for histopathological examination. Cardiac function was quantified using cine imaging and IMH/edema using T2 mapping, and infarct/MVO using late gadolinium enhancement. @*Results@#The extent of infarction (p < 0.001), edema (p < 0.001), IMH (p = 0.013), and MVO (p = 0.049) was less severe in the APT102 group than in the control group. IMH size at 48 hours was significantly greater than that at 24 hours, 72 hours, and 5 days after reperfusion (all p < 0.001). The left ventricular ejection fraction (LVEF) was significantly greater in the APT102 group than in the control group (p = 0.006). There was a negative correlation between LVEF and IMH (r = -0.294, p = 0.010) and a positive correlation between IMH and MVO (r = 0.392, p < 0.001). @*Conclusion@#APT102 can significantly alleviate damage to the ischemic myocardium and microvasculature. IMH size peaked at 48 hours post reperfusion and IMH is a downstream consequence of MVO. IMH may be a potential therapeutic target to prevent adverse remodeling in MI.

Blood-Brain Barrier Disruption and Perivascular Beta-Amyloid Accumulation in the Brain of Aged Rats with Spontaneous Hypertension: Evaluation with Dynamic Contrast-Enhanced Magnetic Resonance Imaging

OBJECTIVE: Whether blood-brain barrier (BBB) disruption induced by chronic spontaneous hypertension is associated with beta-amyloid (Aβ) accumulation in the brain remains poorly understood. The purpose of this study was to investigate the relationship between BBB disruption and Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension. MATERIALS AND METHODS: Five aged spontaneously hypertensive rats (SHRs) and five age-matched normotensive Wistar-Kyoto (WKY) rats were studied. The volume transfer constant (Ktrans) obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to evaluate BBB permeability in the hippocampus and cortex in vivo. The BBB tight junctions, immunoglobulin G (IgG), Aβ, and amyloid precursor protein (APP) in the hippocampus and cortex were examined with immunohistochemistry. RESULTS: As compared with WKY rats, the Ktrans values in the hippocampus and cortex of the SHRs increased remarkably (0.316 ± 0.027 min−1 vs. 0.084 ± 0.017 min−1, p < 0.001 for hippocampus; 0.302 ± 0.072 min−1 vs. 0.052 ± 0.047 min−1, p < 0.001 for cortex). Dramatic occludin and zonula occludens-1 losses were detected in the hippocampus and cortex of SHRs, and obvious IgG exudation was found there. Dramatic Aβ accumulation was found and limited to the area surrounding the BBB, without extension to other parenchyma regions in the hippocampus and cortex of aged SHRs. Alternatively, differences in APP expression in the hippocampus and cortex were not significant. CONCLUSION: Blood-brain barrier disruption is associated with Aβ influx and accumulation in the brain of aged rats with chronic spontaneous hypertension. DCE-MRI can be used as an effective method to investigated BBB damage.

Self-Gated Late Gadolinium Enhancement at 7T to Image Rats with Reperfused Acute Myocardial Infarction

OBJECTIVE: A failed electrocardiography (ECG)-trigger often leads to a long acquisition time (TA) and deterioration in image quality. The purpose of this study was to evaluate and optimize the technique of self-gated (SG) cardiovascular magnetic resonance (CMR) for cardiac late gadolinium enhancement (LGE) imaging of rats with myocardial infarction/reperfusion. MATERIALS AND METHODS: Cardiovascular magnetic resonance images of 10 rats were obtained using SG-LGE or ECG with respiration double-gating (ECG-RESP-gating) method at 7T to compare differences in image interference and TA between the two methods. A variety of flip angles (FA: 10°–80°) and the number of repetitions (NR: 40, 80, 150, and 300) were investigated to determine optimal scan parameters of SG-LGE technique based on image quality score and contrast-to-noise ratio (CNR). RESULTS: Self-gated late gadolinium enhancement allowed successful scan in 10 (100%) rats. However, only 4 (40%) rats were successfully scanned with the ECG-RESP-gating method. TAs with SG-LGE varied depending on NR used (TA: 41, 82, 154, and 307 seconds, corresponding to NR of 40, 80, 150, and 300, respectively). For the ECG-RESP-gating method, the average TA was 220 seconds. For SG-LGE images, CNR (42.5 ± 5.5, 43.5 ± 7.5, 54 ± 9, 59.5 ± 8.5, 56 ± 13, 54 ± 8, and 41 ± 9) and image quality score (1.85 ± 0.75, 2.20 ± 0.83, 2.85 ± 0.37, 3.85 ± 0.52, 2.8 ± 0.51, 2.45 ± 0.76, and 1.95 ± 0.60) were achieved with different FAs (10°, 15°, 20°, 25°, 30°, 35°, and 40°, respectively). Optimal FAs of 20°–30° and NR of 80 were recommended. CONCLUSION: Self-gated technique can improve image quality of LGE without irregular ECG or respiration gating. Therefore, SG-LGE can be used an alternative method of ECG-RESP-gating.

Preliminary investigation on adenovirus-mediated transferrin receptor reporter gene in colorectal cancer cell MR imaging / 中国介入影像与治疗学

Objective To explore the best multiplicities of infection (MOI),the expression of the target gene and in vitro MR imaging of adenovirus vector-mediated transferrin receptor (TFRC) reporter gene transfection of human colorectal cancer Lovo cells.Methods Lovo cells were transfected with recombinant adenovirus (Ad-TFRC) at 5,10,50,100 MOI to determine the best MOI,and quantitative real-time PCR was performed to detect the eDNA of TFRC.The transfected cells were incubated in the culture medium including Tf-USPIO of various concentrations,and were observed by Prussian blue staining,then the cell viability was evaluated via Trypan blue staining.The labeled cells were scanned with 7.0T MR T2W,T2 map,T2* map sequences,and the signal intensities were analyzed.Results Ad-TFRC were successfully transfected into Lovo cells.The best MOI was 50,and the efficiency of infection was more than 90％.The relative expression amount of TFRC in transfected cells was higher than that in control Lovo cells by real-time quantitive PCR (P＜ 0.01).Prussian blue staining showed numerous blue iron particles in transfected cells when the best labeling concentration was 1.5 μg/ml.Trypan blue staining results of transfected Lovo cells and control Lovo cells was (93.80± 1.60)％ and (95.10±2.30) ％,respectively (P＞0.05).MR imaging in vitro showed that compared with control Lovo cells,the signal intensity decreased on T2WI,T2 map and T2* map sequences in transfected Lovo cells (P＜0.05).Conclusion TFRC reporter gene can be efficiently mediated by adenovirus for expression in Lovo cells.After magnetization labeling,7.0T MR imaging of Lovo cells can be successfully achieved in vitro.

Advance of MRI T1ρ in evaluation of liver fibrosis / 中华核医学与分子影像杂志

Chronic liver disease (CLD) is one of the major public health problems,and liver fibrosis is a common feature of CLD.To date,there is no noninvasive method with high sensitivity and specificity for diagnosing and monitoring liver fibrosis in clinical practice.MRI T1ρ,a new technology developed in recent years,is sensitive to macromolecular (such as protein) composition and proton exchange between water and macromolecules,and therefore may be sensitive for the evaluation of liver fibrosis.This review introduces the principle and state of the art of liver MRI T1ρ technology,and summarizes the applications of MRI T1ρ for evaluation of liver fibrosis.

Investigation of aquaporin-1 expression and diffusion weighted imaging with multiple b values in adrenal gland in a rat model of diabetes mellitus / 中华放射学杂志

Objective To investigate the character of aquaporin-1(AQP-1)expression in adrenal gland in diabetes mellitus and evaluate adrenal gland damage and function alterations by DWI with multiple b values. Methods Twenty male Sprague-Dawley rats were randomly selected by computer and randomized into 2 groups:untreated controls(n=10)and diabetes(DM)(n=10). Rats in diabetes group were fed with high-sucrose and high-fat diet, controls were fed with common diet. After fed with high-sucrose and high-fat diet for 4 weeks, rats in diabetes group were injected with streptozotocin(STZ). Forty days after diabetes induction with streptozotocin(STZ), MR imaging was performed in a 7.0 T scanner. Venous blood from the tails was collected before MRI scan to measure blood glucose, blood glucose more than 16.7 mmol/L wasregarded as diabetic status. All the rats underwent DWI with 18 b values(0 to 4500 s/mm2). Maps of pure diffusion coefficients(D), pseudo-diffusion coefficients(D*)and ultra-high ADC(ADCuh)were acquired. Rats were sacrificed after MRI scan for adrenal gland histopathology, AQP-1 immunohistochemistry analysis and AQP-1 optical density(OD)measurements. Student t test was used to compare the difference of D*, D, ADCuh and OD of AQP-1 between two groups. Results Eight diabetic animals developed hyperglycemia(two rats died during the modeling process). MRI scan was performed in all of the 18 rats. Signal intensity of D*map, D map and ADCuh map decreased gradually. ADCuh increased significantly in DM animals(0.24 ± 0.06) × 10-3mm2/s compared with control animals(0.18 ± 0.07) × 10-3 mm2/s(P0.05). There was a noticeable increase in the AQP-1 labeling in the adrenal cell membrane and cytoplasm in DM animals compared with control animals. DM rats showed an increased OD value of AQP-1 in adrenal gland compared with the control animals(P<0.05). Conclusions We found significantly higher AQP-1 expression in adrenal gland in DM animals compared with controls. Ultra-high b-Values DWI may work as a useful way for noninvasive evaluation the change of adrenal function in DM.

The research of myocardial fibers character in isolated rats heart based on 7.0 T diffusion tensor ;imaging / 中华放射学杂志

Objective Using 7.0 T diffusion tensor imaging(DTI) to study myocardial fibers character in isolated rats heart in aspect of water molecular diffusion, myocardial mechanics and microstructure. Methods Fixed male rats heart (n=10) underwent DTI and the myocardial structures were quantitatively measured by Diffusion Toolkit and Matlab. The characteristic of myocardial fibers arrangement was observed and FA values and ADC values of myocardial fibers, myocardial fibers density and length, mean helix angle of left ventricular were calculated as well. Mean helix angle of anterior wall, ventricular septum, lateral wall and posterior wall of epicardium and endocardium were compared by using one?way ANOVA. Results The SD rats' myocardial fibers appeared in compact and inerratic distribution from epicardium to endocardium. Compared with HE staining, regular direction and arrangement in fibers were showed in myocardial fibers tracer map and tensor map in papillary muscle plane. Quantitative analysis showed that ADC value of SD rats' myocardial fibers was (9.6 ± 3.6) × 10-4 mm2/s, FA value was 0.80 ± 0.04, myocardial fibers density was (981±24) tracks/mm3 and myocardial fibers length was (6.18±1.71)mm. Mean helix angle of left ventricular epicardium to endocardium ranged from-81.37° to 0° and then gradually change to 82.83° . There were no significant differences in mean helix angle of anterior wall, ventricular septum, lateral wall and posterior wall of epicardium and endocardium, respectively (F=2.25, 0.40, P>0.05). Conclusions This study shows that DTI is an effective method to quantitatively measure the characteristics of myocardial fibers. This study provides useful information for further study of myocardial fibers in heart disease models.

Evaluation of the Differences of Myocardial Fibers between Acute and Chronic Myocardial Infarction: Application of Diffusion Tensor Magnetic Resonance Imaging in a Rhesus Monkey Model

OBJECTIVE: To understand microstructural changes after myocardial infarction (MI), we evaluated myocardial fibers of rhesus monkeys during acute or chronic MI, and identified the differences of myocardial fibers between acute and chronic MI. MATERIALS AND METHODS: Six fixed hearts of rhesus monkeys with left anterior descending coronary artery ligation for 1 hour or 84 days were scanned by diffusion tensor magnetic resonance imaging (MRI) to measure apparent diffusion coefficient (ADC), fractional anisotropy (FA) and helix angle (HA). RESULTS: Comparing with acute MI monkeys (FA: 0.59 ± 0.02; ADC: 5.0 ± 0.6 × 10(-4) mm2/s; HA: 94.5 ± 4.4°), chronic MI monkeys showed remarkably decreased FA value (0.26 ± 0.03), increased ADC value (7.8 ± 0.8 × 10(-4) mm2/s), decreased HA transmural range (49.5 ± 4.6°) and serious defects on endocardium in infarcted regions. The HA in infarcted regions shifted to more components of negative left-handed helix in chronic MI monkeys (-38.3 ± 5.0°-11.2 ± 4.3°) than in acute MI monkeys (-41.4 ± 5.1°-53.1 ± 3.7°), but the HA in remote regions shifted to more components of positive right-handed helix in chronic MI monkeys (-43.8 ± 2.7°-66.5 ± 4.9°) than in acute MI monkeys (-59.5 ± 3.4°-64.9 ± 4.3°). CONCLUSION: Diffusion tensor MRI method helps to quantify differences of mechanical microstructure and water diffusion of myocardial fibers between acute and chronic MI monkey's models.