With the development of life science and medical technology,myocardial fibrosis is being increasingly recognized as a new therapeutic target for heart diseases.However,traditional methods for detection of myocardial fibrosis,such as myocardial biopsy and laboratory assay of serum metabolites or enzymes,are not satisfactory in meeting the clinical demands because of their intrinsic limitations.Molecular imaging may non-invasively and quantitatively evaluate the presence/absence,degree and turnover of myocardial fibrosis in vivo with good specificity,thus being useful for clinical assessment and intervention.Currently,the commonly used molecular imaging modalities for evaluation of myocardial fibrosis include SPECT,PET and MRI.It is hopeful that the molecular probe for targeted ultrasound technology may also be developed in the near future.This review highlights the current status and future trends of molecular imaging in myocardial fibrosis.

Objective To construct adenovirus vector containing firefly luciferase reporter gene (AdLuc) and infect bone marrow mesenchymal stem cells (BMSC),then to take bioluminescence imaging in vitro and in vivo for identification.Methods The luciferase gene was amplified with PCR from psiCHECK-2 plasmid and cloned into the adenoviral shuttle vector (pShuttle-CMV).It was confirmed by Nhe Ⅰ/Xba Ⅰ digestion and sequencing.PShuttle-CMV-Luc and backbone vector (pAdeno) were homologous recombined.Then the recombinant plasmid was packaged in HEK293 cells and the virus titer was detected.The BMSC were infected by the recombinant adenovirus.The bioluminescence imaging in vitro was performed to determine the best multiplicity of infection (MOI),and the relationship between bioluminescence intensity and MOI was analyzed by curve fitting regression analysis.Viability was evaluated via Trypan blue staining.The transfected BMSC (l× 106) were implanted into the muscles of forelimb of SD rats,and then tracked by bioluminescence imaging in vivo.Cell viability was compared using two-way repeated measures analysis of variance between groups.Results Enzyme digestion and sequence analysis indicated that Ad-Luc was successfully constructed.The virus titer was 1 × 1010 plaque forming unit (PFU)/ml.The bioluminescence detection in vitro showed that Ad-Luc could infect BMSC high efficiently to express luciferase and the best MOI was 50.The bioluminescence intensity enhanced with increase of MOI (R2 =0.98).No statistically significant difference was found in cell viability between transfected and untransfected BMSC at 1,3,5,7 d.The cell survival rates were (92.5±2.3)％ vs (94.1±1.8)％,(91.4±0.9)％ vs (92.7±2.0)％,(92.1±1.6)％ vs (93.3± 2.4) ％,(91.9 ± 1.5) ％ vs (93.0 ± 3.1) ％,respectively (F =4.38,P ＞ 0.05).The bioluminescence imaging in vivo showed that BMSC survived 1,3,7 d after implantation.However,bioluminescence signal decreased gradually over time.Conclusion It is feasible to apply the optical reporter gene imaging for tracing transplanted stem cells in vitro and in vivo due to the effective transformation of luciferase reporter gene into BMSC by adenovirus vector.

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.

ObjectiveA comparison between intragate and ECG-respiration triggered techniques was performed to determine their differences in measuring the structure and function of the heart at 7.0 T.MethodsTen normal ICR mice aged five to six weeks were examined on a 7.0 T MR scanner.A central slice with papillary muscle included at the short-axis view was scanned with a FLASH-cine bright blood sequence,FLASH-cine black blood sequence,IG-FLASH-sat-cine black blood sequence,and IG-FLASH-cine bright blood sequence.The area of the left ventricle of the end systole and end diastole ( including and excluding the myocardium) was measured with manually outlined ROIs.The increased area of the left ventricle and the myocardium from the end systolic to end diastolic phases was calculated.The signal intensity was measured from 8 ROIs which were evenly located at the myocardium of the end systole,and the mean and standard deviation were then determined.The coefficient of variation ( CV ) was derived by dividing the mean into the standard deviation.ResultsThere was no significant difference ( the increased area of the myocardium t =0,P =1,the increased area of the left ventricle t =2.12,P =0.06) in the function index between the ECG-triggered black blood sequences [the increased area of the myocardium (0.100 ±0.018) cm2,the increased area of the left ventricle (0.060 ± 0.024) cm2] and intragate black blood sequences[the increased area of the myocardium (0.090 ± 0.014) cm2,the increased area of the left ventricle (0.060 ±0.012) cm2].No significant difference(the increased area of the myocardium t =1.56,P =0.15,the increased area of the left ventricle t =2.08,P =0.07 ) in the function index was observed between the ECG-triggered bright blood sequences [the increased area of the myocardium ( 0.100 ±0.018) cm2,the increased area of the left ventricle(0.060 ±0.014) cm2]and intragate bright blood sequences [the increased area of the myocardium (0.090 ±0.019) cm2,the increased area of the left ventricle (0.050 ±0.015) cm2].Furthermore,there was no significant difference(t =1,P =0.34) in the CV of the myocardium signal intensity of bright blood sequences between the ECG-triggering ( 0.050 ± 0.013 ) and intragate (0.040 ± 0.015 ),but significant difference ( t =4.51,P =0.001 ) in the CV of the myocardium signal intensity of black blood sequences between the ECG-triggering ( 0.070 ± 0.033 ) and intragate ( 0.160 ± 0.046 ) was obtained.ConclusionsThe intragate sequences could take the place of the ECG gate sequences in functional analysis of the heart( including bright blood and black blood sequences).The bright blood intragate sequences also could replace the bright blood ECG-triggered sequences in analyzing the signal of the myocardium.

Objective To determine the value of CT and MRI in the evaluation of littoral cell angioma(LCA) of spleen.Methods Two experienced radiologists retrospectively analyzed the clinical data,CT and MRI findings of 12 patients with pathology proven LCA of spleen.The patients underwent noncontrast enhanced CT scan,then enhanced CT (n =10) and MRI (n =3) were performed.Results The majority of patients (8/12) showed splenomegaly,with no obvious signs and symptoms of hypersplenism.The majority of patients (10/12) had the uncountable hypodense lesions,a few (2/12) had only a single lesion.None of the lesions contained any calcification or envelopement.On CT,the majority (7/10) of the lesions demonstrated well circumscribed border,with some lesions (3/10) demonstrating a less distinct border.The enhanced scan for low-density nodules demonstrated slow progressive enhancement.On MRI,all the LAC had well circumscribed borders,and demonstrated T1-hypointense and T2-hyperintense signalswith punctual hypointense in the T2 WI,and progressive enhancement on the post contrast images.DWI showed an increased diffusion of the lesions compared to the normal appearing splenic tissue.Conclusion CT and MR imaging of littoral cell angioma of spleen has certain imaging characteristics,those particular findings may potentially aid in the diagnosis.

Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i. e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.
Cell Line, Tumor ; Colonic Neoplasms ; diagnosis ; Ferric Compounds ; Humans ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; chemistry ; Molecular Imaging ; methods ; Receptors, Urokinase Plasminogen Activator ; chemistry ; Staining and Labeling

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(P<0.05), whereas there was no significant difference found between the two groups in their respective D*and D values(P>0.05). 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.

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.

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.

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.