When insonated with fundamental frequency, the ultrasound contrast microbubbles are able to produce nonlinear scattering and generate nonlinear frequencies. The nonlinear properties of these microbubbles can be used to create nonlinear imaging modality and significantly improve the diagnostic capability of medical ultrasound. This paper was a review about the current research progress of nonlinear properties of ultrasound contrast microbubbles and nonlinear imaging, especially about the nonlinear properties under different frequency, acoustic pressure and the application of nonlinear imaging. A prospect of the future research and application was finally put forward in the paper.

The development and progression of atherosclerosis and thrombosis are closely related to changes of hemodynamics parameters. Ultrasonic pulse wave Doppler technique is normally used for noninvasively blood flow imaging. However, this technique only provides one-dimensional velocity and depends on the angle between the ultrasound beam and the local velocity vector. In this study, ultrasonic particle image velocimetry method was used to assess whole field hemodynamic changes in normal blood vessels. By using the polynomial fitting method, we investigated the velocity gradient and assessed the shear in different blood flow velocity of 10 healthy rats. It was found that using four polynomial fitting could result in optimal measurement results. The results obtained by ultrasonic particle image velocimetry accorded with the results obtained using Doppler technique. The statistical average of cyclical vessel wall shear stress was positively related to the locational mean velocity. It is proven that ultrasonic particle image velocimetry method could be used to assess directly the real-time whole field hemodynamic changes in blood vessels and was non-invasively, and should be a good prosperous technique for monitoring complex blood flow in stenotic ar- teries.
Algorithms ; Animals ; Arteries ; diagnostic imaging ; pathology ; Blood Flow Velocity ; Echocardiography, Doppler ; Hemodynamics ; Models, Cardiovascular ; Rats ; Rheology ; Stress, Mechanical ; Ultrasonics

Objective To investigate the role of intestinal immune dysfunction in the pathogenesis of irritable bowel syndrome(IBS) and to study the effects of Clostridium butylicum on the regulation of intestinal immune disorders.Methods A total of 50 male 6-week-old C57BL/6 mice were randomly divided into three groups,including the experimental group (n =20),the control group (n =20) and the Clostridium butylicum group(n =10).A mouse model of constipation-predominant IBS (C-IBS) was established by perfusing sodium butyrate solution(200 μl,concentration of 500 mmol/L) into the mouse colon twice a day for three consecutive days.The mice in control group were intrarectally perfused with normal saline enema (200 μl).Two hours before the perfusion of sodium butyrate into colon,the mice in Clostridium butylicum group were given Clostridium butylicum 500 μl(viable cell concentration of 1×109 CFU/ml) by oral gavage once a day for six days.The colorectal distention test(CRD) was carried out for evaluation of clinical parameters.HE staining of intestinal tissue section was performed for histopathological assessment of colonic mucosal inflammation.Intestinal intraepithelial lymphocytes (IELs) and lamina propria mononuclear cells (LPMCs) were isolated and analyzed by flow cytometry to evaluate the correlation between IBS and intestinal immune dysfunction/abnormal activation of intestinal immune cells in mouse model of C-IBS,and to assess the regulatory effects of Clostridium butylicum on the intestinal immune disorder.Results (1) Compared with the control group,the mice in experimental group showed a significant change in physiological parameters,histological structure of colon,inflammatory cells infiltration and low-grade inflammatory state.There was a significant increase in scores of CRD and a decrease in lowest sensory threshold (t=8.926 and t=6.103,both P＜0.001) ; (2) There was a decrease in the numbers of DC in IELs (t =2.878 and t =3.086,both P＜0.05),but an increase in the numbers of macrophage (t=3.191,P＜0.05) and the memory T cells in mice with IBS (t=3.071,P＜0.05) as compared with that in control group; (3)DCs were decreased (t=2.880 and t=2.664,both P＜0.05),but memory T cells were increased (t =3.732 and 2.682,P＜0.01 and P＜0.05) in the LPMCs of mice in experimental group; (4)There was no significant difference in the physiological index between the mice in control group and the Clostridium butylicum group.Levels of memory T cells,macrophages and DCs in the IELs were close to the normal level (6 d,t =1.103,0.0213,0.418,all P＞0.05),and levels of macrophages and DCs in the LPMCs of mice in the Clostridium butylicum group were also similar to that in the control group (6 d,t =0.782,0.347,both P＞0.05) ; (5) Compared with the mice in experimental group,the level of memory T cells in LPMCs of mice treated with Clostridium butylicum was dramatically declined (6 d,t=2.346,P=0.0470,P＜0.05),however,which was still higher than that of mice in control group (6 d,t =2.233,P =0.0476,P＜0.05).The intestinal immune function was restored to normal level with Clostridium butylicum intervention.Conclusion The pathophysiologic mechanism of IBS might be closely related to the abnormal activation of intestinal immune cellsand disordered functional state in the intestinal mucosa.Clostridium butylicum could regulate the intestinal immune homeostasis and restore the physiological function of gastrointestinal tract.

Objective To evaluate the safety and possibility of transesophageal emergency ventricular pacing with esophageal balloonelectrode catheter.Methods Sixty four patients with critical bradyarrhythmias were divided randomly to receive either transesophagealventricular pacing with esophageal balloon electrode catheter(balloon.catheter group,n=32),or transesophageai ventricular pacing withnormal esophageal electrode catheter(normal catheter group,n=32).Pulse width(ms),current output(mA),and the success rate werecompared between the 2 groups.Results Success rate in the balloon catheter group was 87.5%,which was significantly higher thanthat in the nodal catheter group(18.7%,X2=27.7,P＜0.01).The success rate oftransesophageal ventricular pacing with esophagealballoon electrode catheter was 87.5%.The average current output(mA)was significantly lower in the balloon catheter group than thatin the normal catheter group (24.5+2.5 mA VS 53±3.4mA,P＜0.05).Conclusions Esophageal balloon electrode catheter pacing couldbecome an available teclmiqBe for transesophageal emergency ventricular pacing.

OBJECTIVE:To study the protective effects of total flavone from Prunus cerasifera fruits(PCE)on alcoholic liver disease(ALD)in rats,and provide experimental basis for developing new medicines for anti-ALD. METHODS:40 rats were ran-domly divided into normal group(distilled water),model group(distilled water),silibinin group [positive control,30 mg/(kg·d)] and PCE high-dose,low-dose groups [80,40 mg/(kg·d)],8 in each group. All rats were intragastrically administrated(10 mL/kg) every morning,once,for 6 weeks;meanwhile,except for normal group,rats in other groups received 50% alcohol(10 mL/kg) once intragastrically every afternoon to induce ALD model. After administration,heart,liver,spleen and other organ indexes,sub-cutaneous fat,brown fat,abdominal fat indexes were determined,as well as serum biochemical indexes [glutamate transaminase (ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),direct bilirubin(DBIL),indirect bilirubin(IBIL),gamma-glu-tamyl transpeptidase(GGT),and total cholesterol(TC),triglyceride(TG),high-density lipoprotein(HDL),low-density lipopro-tein (LDL)] level and liver biochemical indexes [superoxide dismutase (SOD),malondialdehyde (MDA),glutathione peroxidase (GSH-Px),TC,TG] and TC,TG levels in feces;pathological changes of liver and kidney tissues were observed. RESULTS:Compared with normal group,heart,liver,spleen indexes,subcutaneous fat,abdominal fat indexes in model group were in-creased(P<0.05 or P<0.01),brain index and brown fat index were decreased(P<0.05);HDL level and HDL/TC ratio in serum were decreased,other serum indexes were increased(P<0.05 or P<0.01);SOD,GSH-Px levels in liver tissue were decreased, other above-mentioned liver biochemical indexes were increased(P<0.01);TC,TG levels in feces were increased(P<0.01);liv-er and kidney showed obvious lesions. Compared with model group,the above-mentioned indexes in silibinin group and PCE high-dose group were significantly improved (P<0.05 or P<0.01);ALT,AST in serum and MDA level in liver tissue in PCE low-dose group were significantly decreased(P<0.01),and SOD,GSH-Px levels in liver tissue were significantly increased(P<0.05);lesion degree of liver and kidney and lipid accumulation in liver were reduced in administration groups. CONCLUSIONS:PCE may play a role in anti-ALD by anti-oxidation,promoting liver cell regeneration and regulating lipid metabolism.

Objective To explore the characteristics of gait of old hemiplegic patients. Methods 22 old hemiplegic patients were investigated with Motion Analysis. Results The bilateral support phase increased, especially for the affected lateral. The swing phase decreased, as well as the frequency, step length, stride length and walking speed. Their heads flexed forward, but trunks remained upright. The motion of range of shoulder and elbow decreased in the affected lateral (P<0.05), and the angle of flexion and adduction in the affected shoulder and flexion in elbow increases (P<0.05). The motion of range of the affected hip, knee and ankle decreased (P<0.05). Conclusion The walking ability impaired in the old hemiplegic patients, with upper limbs spasticity, vision compensation, etc.

Objective To investigate the effects of ischemic preconditioning on pneumocyte apoptosis and the expression of HSFT0 after lung isehemia-reperfusion(I/R) in rats and discuss its possible mechanism of extenu-ating ischemia-repedusion injury. Method Thirtysix male Sprague-Dawley rats were randomly divided into three groups [ sham operation(SO ) group, ischemia-teperfusion(L/R) group, and ischemic preconditioning(IP) group],twelve in each group. Lung croas-clamping was used to build the L/R model. In IP group, three cycles of 5-minute-ischemia + 5-minute-reperfusion were given to the pulmonary artery before the procedure. Sham operation rats had a thoracotomy only. Two hours(or five hours) reperfusion was given to both L/R and IP group. Tenninal-deoxynucleotidyl Transferase Mediated d-UTP Nick End Labeiing(TUNEL) was used to evaluate apoptosis. Expression of HSP/0 in lung was observed by immunohistochemical stain and image analysis. Index of quantitative assessment of histologic lung injury(IQA), wet to dry weight ratio(W/D) were measured. The pathological change of lung tissue was observed under both hght and electron microscopy. Statistical analysis was carried out by One-way Anova. Scheffe test was used for intragroup comparison. Results The apoptosis index and expression of HSP70、W/D,IQA of hng tissue in I/R group were higher than those in the sham operation group (P<0.01). Compared with the L/R group, the apoptosis index and expression of HSP70, W/D, IQA of lung tissue significantly decreased (P<0.01), the levels of expression of HSPTO increased significantly in IP group ( P<0.01 ). The pathological and ultrastructure change of lung tissue was better in IP group than those in I/R group. Condusions Ischemic preconditioning can extenuate lung I/R injury by the possible mechanism of increasing the expression of HSPT0 which inhibits the apoptosis during lung I/R injury.

Objective To improve the diagnostic ability of leukoencephalopathy with cerebral calcifications and cysts (LCC),a rare central nervous system disease.Methods The clinical manifestations,neuroimages and neuropathological features of a 19-year-old male patient were analyzed.A total of 20 cases from 14 literatures were reviewed.Results The patient was admitted with right limb weakness,cognitive decline,headache and blurred eyesight.Head CT scan showed multiple calcifications,cysts formation and leukoencephalopathy.Brain MRI showed several cysts in bilateral hemisphere,basal ganglia,thalamus and paraventricular areas.A mural nodule was noted inside one of the cyst,which was enhanced on the contrasted MRI.The wall of the cysts was partially enhanced,but not with the fluid inside the cysts.The corresponding CT calcifications foci showed on T1 and T2 with either both hyperintensity or both hypointensity,which was also partial enhanced.Extensive leukoencephalopathy was formed around the cysts and the ventricles.But neither Cho nor NAA changed a lot on MRS.Amplitude diagram of SWI series exhibited multiple round small dark signals all over the affected areas with mixed signals showed in the phase diagram,which indicated both calcifications and microbleedings at the lesions.Neuropathological examinations found no tumor cells in the operated cyst,and showed angiomatous small blood cells were dominant in the cyst wall.Hyaline degenerations,microcalcifications and hemosiderin deposition were observed.No obvious demyelination was discovered,while gliosis,numerous Rosenthal fibers and fibrinoid vascular necrosis were found around the lesions.The clinical,neuroimaging and pathological features of this patient were in accordance with the cases reported in the literatures.Conclusions Neuroimaging is the most important method for the diagnosis of LCC.As small vessel lesions are probably closely related to the pathophysiology of LCC,SWI could be recommended to further reveal the etiology of LCC.

Objective To prepare urokinase plasminogen activator (uPA)-loaded anionic lipid microbubbles (uPA-MBs) for thrombolysis with low-frequency ultrasound in vitro.Methods Anionic microbubbles composing of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC),1,2-dipalmitoyl-sn-glycero-3-phospho-(l'-rac-glycerol) (DPPG),1,2-distearoyl-sn-glycero-3-phosphoethanol amine-N (succinyl PEG2000) (DSPE-PEG2000) and perfluoropropane (C3F8) were prepared by the mechanical vibration method.Then,the resulting anionic microbubbles were incubated with uPA.uPA-MBs were obtained via electrostatic adsorption.Bubble size and distribution were measured by particle size analyzer.FITC-labeled uPA-MBs were obtained and observed under fluorescence microscope.The surface potential of uPA-MBs and plain microbubbles (P-MBs) were detected by Zeta potential analyzer.Sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) was used for confirming the binding of uPA protein and anionic microbubbles.The encapsulation efficiency of uPA-MBs was determined by bicinchoninic acid (BCA) protein assay kit under three different dosages of uPA (10 000,50 000 and 100 000 U).The thrombolysis efficiency of uPA-MBs combined with low-frequency ultrasound was examined in vitro.Two-sample t test,one-way analysis of variance and Bonferroni test were performed to analyze the data.Results UPA-MBs were successfully obtained with the mean particle size of (1.76±0.29) μm.The surface potential of these bubbles was significantly higher than that of P-MBs:(-36.64±0.21) mV vs (-66.33±2.38) mV (t =21.538,P＜0.05).Fluorescence microscope showed a green shell of FITC-labeled uPA-MBs.The encapsulation efficiency of uPAMBs with the added dosage of 10 000 U was (42.01±2.02) ％,which was significantly higher than those of 50000 and 100 000 U ((33.24±1.95)％ and (33.10±1.65)％ respectively,F=22.340,P＜0.05).The thrombolysis efficiency by saline was (4.09±0.80)％,saline + ultrasound (8.50±1.48)％,MBs + ultrasound (14.27± 1.59) ％,uPA-MBs + ultrasound (35.72±6.31) ％ and uPA (16.87±0.46) ％,respectively (F =48.783,t =-8.613,-7.273,-5.942,-6.908,all P＜0.05).Conclusion Anionic microbubbles can successfully load uPA,and achieve significantly better thrombolysis effect when combined with low-frequency ultrasound.

Objective To evaluate the effectiveness of treating glioma in combination of two kinds of drugs by comparing the size of tumors and the survival time of different groups in rat glioma after targeted blood‐brain barrier (BBB) disruption by focused ultrasound under MRI‐guide. Methods The stereotaxis instruments and the 10 μl gas‐tight syringes were used to inject gliosarcoma cells into the targeted area of the brain in 40 male Sprague‐Dawley rats. The glioma‐bearing rats models were established. Rats were divided into 4 groups to receive different treatment :(1) no treatment (control, n = 8), (2) IV Avastin (Avastin only, n =10), (3) IV liposomal doxorubicin (DOX only, n =10), (4) IV Avastin and liposomal doxorubicin (Avastin+DOX, n =10). The SonoVue microbubbles and DOX or Avastin were injected into the tail vein respectively on the 12th day after implantation. The tumor size was measured by MRI on immediacy, once a week after targeted BBB disruption by focused ultrasound, and the life span in rat glioma was recorded. Results The average survival time of different groups in rat glioma was as follows :no treatment(17 ± 4)d, Avastin(20 ± 4)d, DOX(25 ± 5)d, DOX+ Avastin(40 ± 5)d. The tumor size after post‐treatment of different groups in rat glioma was as follows :no treatment(5 7.0 ± 4 3.0)mm, Avastin(4 3.0 ± 2 5.0)mm, DOX(4 1.2 ± 3 1.0)mm, DOX + Avastin(2. 20 ± 1. 30)mm. There was significant increased in average survival time and decreased in tumor size after a combination treatment DOX+ Avastin compared with other groups( P < 0 0.1). Conclusions The microbubble blasting by MRI‐guided focused ultrasound enhances the local tissue permeability and promotes the drug delivery of chemotherapy and anti‐angiogenesis locally in glioma‐bearing rats. Especially, the combination of two kinds of drugs has a synergism efficacy that may reduce tumor growth and increase survival time significantly after BBB disruption.