当前位置:文档之家› Angiogenesis by Contrast-enhanced Gray-scale Sonography in Antigen-induced Arthritis in Rabbits

Angiogenesis by Contrast-enhanced Gray-scale Sonography in Antigen-induced Arthritis in Rabbits

Angiogenesis by Contrast-enhanced Gray-scale Sonography in Antigen-induced Arthritis in Rabbits
Angiogenesis by Contrast-enhanced Gray-scale Sonography in Antigen-induced Arthritis in Rabbits

Noninvasive Quantitative Assessment of Synovial Pannus Angiogenesis by Contrast-enhanced

Gray-scale Sonography in Antigen-induced Arthritis in Rabbits Yong Jiang,MD,Li Qiu,MD,Lingyan Zhang,MD,Yan Luo,MD,Ling Lin,MD,Xiaorong Wen,MD Rationale and Objectives:The aim of this study was to evaluate the value of contrast-enhanced gray-scale sonography in quantitative assessment of synovial pannus angiogenesis in antigen-induced arthritis in rabbits.

Materials and Methods:Twenty-four adult New Zealand White rabbits were divided into two groups.In?ammatory arthritis was induced by intra-articular injection of ovalbumin into right knee joints with4mg in low-dose group(LD,n=12)and8mg in high-dose group(HD,n=12). The left side of the knee on each rabbit was used as normal control.Contrast-enhanced gray-scale sonography with time intensity curve (TIC)was performed on the synovia of suprapatellar bursa and posterior capsules4weeks after the injection.Immunohistochemical examinations of synovia were applied to assess the microvessel density and the expression of vascular endothelial growth factor. Correlation analysis between sonographic and immunohistochemical?ndings was performed.

Results:Contrast-enhanced gray-scale sonography of all right knees demonstrated intra-articular hypoechoic lesions with enhanced blood?ow and no abnormal?ndings on all left knees.Parameters of TIC,including ascending curve(A),derived peak intensity(DPI), and area under curve(AUC)on arthritis joints were signi?cantly higher in HD group compared to LD group(P<.05).Positive correlation was found between immunohistochemical?ndings and parameters of A,DPI,and AUC(P<.05).However,no correlation was found between other parameters(slope of descending rate,time to peak,time to rise,and initial intensity)and immunohistochemical?ndings.

Conclusions:Contrast-enhanced gray-scale sonography with TIC measurement could provide reliable method for noninvasive quantitative assessment of synovial pannus angiogenesis of arthritis in clinical settings.

Key Words:Contrast-enhanced gray-scale sonography;quantitative assessment;time intensity curve;antigen-induced arthritis; synovial pannus angiogenesis.

aAUR,2011

R heumatoid arthritis(RA)is a chronic systematic autoimmune disorder that principally attacks synovial

joints,especially small joints of the hands and feet.It is mainly characterized by massive synovial proliferation and changes in synovial architecture resulting in interdigitating folds of tissue,termed pannus.Recurrent in?ammation leads to the destruction of the cartilage,bones,and ligaments, causing deformity and loss of function.The formation of active in?amed pannus is central to this erosive disease.Synovial vascularity is correlated with disease activity and response to therapy(1,2).Studies showed that angiogenesis was regulated by a complex set of inducers and inhibitors. Of these,vascular endothelial growth factor(VEGF)is a potent endothelial cell–speci?c growth factor involved in in?ammatory activities.However,histologic measurement of microvessel density(MVD)and VEGF of synovial tissue is invasive and impractical in clinical settings(3–5). Therefore,the introduction of a noninvasive and ef?cient alternative is of great important and necessary.

The development of color and power Doppler sonography was a complement of the conventional gray-scale sonography. However,sensitivity and quanti?cation cannot be perfectly achieved by these imaging techniques.The introduction of contrast-enhanced gray-scale sonography has made imaging of synovial microvessels possible.This imaging technique exploits the nonlinear oscillations of microbubbles that produce harmonic overtones of the original sound wave(6–8).It

Acad Radiol2011;18:359–368

From the Departments of Pathology(Y.J.)and Ultrasound(L.Q.,L.Z.,Y.L.,L.L.,

X.W.),West China Hospital of Sichuan University,No.37Guo Xue Xiang,

Chengdu610041,Sichuan,China.Received September2,2010;accepted

October20,2010.Supported by grants from National Natural Science

Foundation of China(30801067)and Sichuan Science and Technology Plan

(06SG1589).Address correspondence to:L.Q.e-mail:wsqiuli@https://www.doczj.com/doc/7210933003.html,

aAUR,2011

doi:10.1016/j.acra.2010.10.007

359

allows dynamic measurement of region of interest (ROI)to achieve quantitative assessment of blood ?ow in synovial pannus at the microvascular level (7).However,there were de?cient studies using quanti?cation parameters of time-intensity curve (TIC)for assessing the degree of RA.The following questions have to be addressed before its clinical application.Can the TIC parameters achieved from contrast-enhanced gray-scale sonography quantitatively evaluate the activity and the treatment effectiveness of RA?Is it possible,hence,with the new method to display the microperfusion of synovial pannus,to determine the valuable parameters to assess the activity of RA?

The present study was to compare the contrast-enhanced gray-scale sonography and immunohistochemical ?ndings using the antigen-induced arthritis rabbit models.Correlation of TIC parameters and MVD/VEGF were performed to determine the value of contrast-enhanced gray-scale sonog-raphy in assessing synovial pannus and disease activity.

MATERIALS AND METHODS

Antigen-induced Arthritis Model in the Rabbit Joint

T wenty-?ve adult New Zealand White rabbits (2.5to 3.0kg)were used to create an arthritis model for this study.Rabbits were raised under routine conditions.All experiments were approved by the institutional animal use committee and performed in accordance with the guidelines of Department of Animal Resources at Sichuan University.

According to previously established methods,4mg ovalbumin (OVA,Sigma,St Louis,MO)was dissolved into 0.5mL Freund’s complete adjuvant (F-5881,Sigma Chemical Co)and 0.5mL phosphate-buffered saline.The emulsi?ed mixture was injected into ?ve subcutaneous sites in the interscapular area for three times at an interval of 7days for sensitization (9,10).Five days after last subcutaneous injections,intra-articular injections of ovalbumin/saline (0.5mL)were conducted in the right side of the knee with dosages of 4mg in the low-dose group (LD,n =12)and 8mg in the high-dose group (HD,n =13)to induce in?ammatory arthritis.The left side of the knee without injection on each rabbit was used as normal control.One rabbit in HD group died at day 5after intra-articular injection.Thus,a total of 24rabbits were used for imaging and pathologic evaluation.

Contrast-enhanced Sonographic Technique

Contrast-enhanced gray-scale sonography was performed using iU22ultrasound system (Phillips Medical System,Bothell,WA)4weeks after intra-articular injection.With the use of a

L9-3

Figure 1.Contrast-enhanced gray-scale sonography with time intensity curve (TIC)measurements.Longitudinal images (a,b)of the right suprapatellar bursa and transverse imagines of the right posterior capsule (c,d)obtained from rabbits in low-dose group (LD)and high-dose group (HD),respectively.

JIANG ET AL Academic Radiology,Vol 18,No 3,March 2011

360

broadband linear array transducer,gray-scale pulse inversion harmonic imaging mode was used with the mechanical index of 0.06.All the settings,including depth,gain control,and time gain compensation,were optimized and keep in consis-tency during imaging acquisitions.Baseline imaging of the suprapatellar bursa and posterior capsules on both left and right sides of the knee were obtained using conventional gray-scale sonography .For contrast-enhanced ultrasound evaluation of the knee joint,0.1mL/kg of sulfur hexa?uoride-based ultra-sound agent (SonoVue,Bracco,Milan,Italy)was injected via ear vein in a single bolus,followed by 2mL saline ?ush.Contrast-enhanced dynamic imaging of suprapatellar bursa or posterior capsules of the knee was stored digitally up to 3minutes during the wash-in and wash-out phases.

T o quantitatively analysis of contrast-enhanced ROI,build-in imaging software (Q-Lab,Phillips Medical System)was used for generate the TICs and corresponding parameters.A square ROI

with a size of 1.68mm 2was set in the suprapatellar bursa and posterior capsules that showed the most prominent enhance-ment on gray-scale imaging.The parameters derived from the TIC included slope rate of ascending curve (A),derived peak intensity (DPI),area under curve (AUC),slope rate of descend-ing rate (a ),time to peak (TTP),time to rise (t0),and initial intensity (C).T o evaluate reproducibility ,the measurements were repeated three times.The mean value of these three TICs was utilized for data analysis.Measurements of the TICs were performed independently by two radiologists with more than 8years of ultrasound experience in blinded fashion.

Immunohistochemical Studies of Synovial Pannus

Rabbits were sacri?ced with intravenous injection of overdose pentobarbital at the end of the experiments.At the necropsy ,synovia obtained from suprapatellar bursa and posterior

capsules

Figure 2.Graphs a-g show the comparison of all time intensity curve (TIC)parameters between two groups.The left bar on each pair represent the data from the low-dose group (LD)and the right represent the data from the high-dose group (HD).The black columns indicate the param-eters of the suprapatellar bursa and the gray columns indicate the posterior capsule.Signi?cant differences were observed in parameters of ascending curve (a),derived peak intensity (DPI),area under curve (AUC)between two groups.*P <.05,**P <.01,ns:not signi?cant.

Academic Radiology,Vol 18,No 3,March 2011CONTRAST-ENHANCED SONOGRAPHY ASSESSMENT OF SYNOVIAL ANGIOGENESIS

361

on the right joint of the knee were ?xed in 4%formalin,dehy-drated,and embedded in paraf?n.Serial sections were sliced at 4m m thickness and prepared for immunohistochemical stain-ing.Both MVD and VEGF expressions were analyzed indepen-dently by two pathologists with more than 8years of experience.For the MVD assessment,monoclonal antibody CD31(JC/70A,ab9498,Abcam,Cambridge,MA)speci?cally interacting with CD31receptor on the endothelial cells,can be detected by brown-stained cells (11).Microvessels can be counted as brown-stained endothelial cells within a de?ned border with or without lumens.In brief,MVD was measured by the hotspot method under the microscopy.MVD were counted in three independent views and the mean value was used for further analysis.

For VEGF expression assessment,positive VEGF (JH121,ab28775,Abcam)expression is indicated as brown staining in the cytoplasm (12).Scoring is based on the percentage (P)and intensity (I)of cells in a semiquantitative manner.For this study,the intensity of VEGF staining was scored as 0(nega-tive),1(weak),2(intermediate),or 3(strong).In addition,the percentage of positive cells (P)was scored as 0(no positive cells),1(less than 25%),2(26%to 50%)or 3(greater than 50%).A sum of P and I scores was used to determine the VEGF expression.A sum was scored as 0-2(negative),3-4(weak),or 5-6(strong).

Statistical Analysis

Statistical analysis was accomplished using SPSS 17.0software (SPSS,Chicago,IL).Data were expressed as mean ?SD.Statistical signi?cance among the experimental groups was examined by Mann-Whitney U test.Correlation analysis was analyzed by Spearman test.A P value <.05was consid-ered statistically signi?cant.RESULTS

Comparison of Contrast-enhanced Sonography between Two Groups

Both conventional and contrast-enhanced gray-scale sonog-raphy of the left side of the knee did not showed any evidences of abnormal appearance in suprapatellar bursa and posterior capsules in all

rabbits.

Figure 2.(continued ).

JIANG ET AL Academic Radiology,Vol 18,No 3,March 2011

362

Conventional gray-scale ultrasound of the right knee joint with antigen-induced arthritis showed thickened capsules in suprapatellar bursa and posterior capsule with echo-free area (?uid)or hypoechoic area (synovial hyperplasia)(Fig 1).When the in?ammatory lesion was associated with viscous ?uid,it was dif?cult to differentiate the ?uid from the synovial hyper-plasia.After injection of SonoVue in the LD group,contrast-enhanced gray-scale sonography showed vascular enhancement in 7(58.3%)synovia of suprapatellar bursa and 10(83.3%)posterior capsules.However,in the HD group,the enhance-ment was seen in all synovia of the suprapatellar bursa and posterior capsules (P <.05).

TICs of contrast-enhanced sonography showed dynamic enhancement of the abnormal synovia with wash-in and wash-out perfusion pattern (Fig 1).When comparing parame-ters of the TICs between the LD and HD groups,the slope rate of ascending curve (A),DPI and AUC were statistically signi?cantly higher in the HD group than the LD group (P <.05),whereas no statistically signi?cant difference was observed

in the remaining parameters (ie,a ,TTP ,t0,and C)(P >.005)(Fig 2).

Comparison of Immunohistochemical Findings between Two Groups

MVD and expression of VEGF in the synovia of suprapatellar bursa and posterior capsules were signi?cantly higher in HD group than in LD group (P <.05).These ?ndings indicated that angiogenesis was more substantial in HD group (Figs 3,4).

Correlation between Contrast-enhanced Sonography and Immunohistochemical Findings

Positive correlation was found between immunohistochem-ical ?ndings and certain parameters,including slope rate of A,DPI,and AUC (P <.05;Fig 5).However,no correlation was found between immunohistochemical ?ndings and other parameters (ie,a ,TTP ,t0,C)(P >

.05).

Figure 3.Microscopic views of synovial tissues from arthritis joints.Immunohistochemical staining with CD31antibody showed less neovas-cularities in the low-dose group (LD)(a)than those in the high-dose group (HD)(b).Immunohistochemical staining with vascular endothelial growth factor (VEGF)antibody showed more neovascularities in the LD group (c)than those in the HD group (d).(Magni?cation ?400).

Academic Radiology,Vol 18,No 3,March 2011CONTRAST-ENHANCED SONOGRAPHY ASSESSMENT OF SYNOVIAL ANGIOGENESIS

363

DISCUSSION

RA is a very common chronic disease.It still remains dif?cult to evaluate the in?ammatory activities and disease progression in RA patients.Histologic measurement of MVD and VEGF has been used to assess synovial angiogenesis.Studies showed that synovial angiogenesis was signi?cantly correlated with disease progression (13–15).

Computed tomography and magnetic resonance imaging with contrast enhancement are capable of revealing synovial neovascularization.However,these imaging studies are limited by high cost,radiation side effects,and time-consuming scanning (6,16).Conventional color Doppler imaging is not sensitive enough to detect blood ?ow at low velocity at microvascular levels.With the use of microbubble-based contrast agent,gray-scale sonography can dramatically improve the detection of blood ?ow and to visualize synovial vascularity (17,18).T o further investigate contrast-enhanced sonography to ef?ciently reveal the dynamic changes of synovial vascularity is vital for evaluation RA activity and responses to therapy .Through the extensive research on adolescent RA,Doria et al found that ultrasound contrast imaging can be applied to distin-guish active and nonactive synovitis and assess the ef?cacy of treatment.The blood supply could be reduced after treatment (19,20).Carotti et al reported that the activity of synovitis and treatment effects could be assessed by ultrasound contrast imaging (21).With the use of imaging analysis software,for dynamic measurement of ROI and distribution of contrast agent,investigators had used TIC and corresponding parameters of contrast-enhanced sonography to quantify the microcircula-tion of tumors and organs,such as in muscle,kidney ,ovary ,and liver.Kersting et al found that contrast quanti?cation software is supplement to a subjective visual assessment with objective criteria to facilitate the differential diagnosis of focal lesions in pancreatic cancer and chronic pancreatitis (22).Krix et al found that continuous assessment of local muscle microcirculation during exercise was possible with real-time contrast-enhanced ultrasound with an acceptable robustness (23).Thus,contrast-enhanced sonography is a potential noninvasive alternative

to

Figure 4.Graphs show the comparison of microvessel density (MVD)and vascular endo-thelial growth factor (VEGF)between two groups.The left bar on each pair represent the data from the low-dose group (LD)and the right represent the data from the high-dose group (HD)group.Signi?cant differences in MVD and VEGF were observed between two groups.*P <.05and **P <.01.

JIANG ET AL Academic Radiology,Vol 18,No 3,March 2011

364

ef?ciently monitor microvascular blood ?ow,which is bene?-cial and useful to RA evaluation (24,25).T o our knowledge,quantitative assessment of abnormal synovial blood ?ow using contrast-enhanced sonography and parameters of TIC has not been fully studied.

Antigen-induced arthritis in rabbit joints is an ideal model for ultrasound imaging study .Pathological changes in the antigen-induced arthritis model are similar to that in humans.At 1week after intra-articular injection of ovalbumin,massive lymphocytes in?ltration was observed in the joints whereas at 4weeks,synovial pannus was very prominent (9,10).In our study ,we found that synovial pannus formation was dependent on the dose of antigens injected.In addition,articular anatomic features of rabbits well resemble the joints in humans.Ultrasound imaging is able to reveal the structures of suprapatellar bursa and posterior capsules.Therefore,antigen-induced arthritis rabbit models are suitable for contrast ultrasound imaging study .

In this study ,we found that MVD and VEGF as demonstrated by immunohistochemical examinations were remarkable increased in the HD group.These ?ndings indicated a positive correlation of synovial pannus formation and injection dose of the antigen.On the TICs derived from the contrast imaging,slope rate of A,DPI,and AUC were notably elevated in the HD group compared with the LD group,suggesting a correlation with histological ?ndings.Further analysis revealed a positive correlation of A,DPI,and AUC with MVD and VEGF ,respectively .These ?ndings implicated that these parameters could be used to quantify synovial pannus formation and neovascular status.

Contrast-enhanced sonography with gray-scale pulse inver-sion harmonic imaging mode used in our study can

provides

Figure 5.Graphs show correlations between time intensity curve (TIC)parameters and immunohistochemical ?ndings (microvessel density [MVD]and vascular endothelial growth factor [VEGF]).The graphs of a-j were generated from the suprapatellar bursa and the graphs of c-l were generated from the posterior capsule.Positive correlations were found between parameters of ascending curve (a),derived peak intensity (DPI),area under curve (AUC),and MVD/VEGF.

Academic Radiology,Vol 18,No 3,March 2011CONTRAST-ENHANCED SONOGRAPHY ASSESSMENT OF SYNOVIAL ANGIOGENESIS

365

excellent visualization of synovial vascularity by subtracting the background noise of soft tissue,and thus,increasing the ratio of vascular signals to the background noise.However,this imaging technique can only apply for qualitative evaluation instead of quantitative https://www.doczj.com/doc/7210933003.html,ing a linear correlation between echo intensity and microbubbles of ROI,TIC is able to quantitatively assess contrast-enhanced gray-scale sonography .According to the dilution principle of contrast agents,intensity of contrast agents rises to peak over time and then decrease in a certain ROI.In case of blood ?ow at higher velocity ,the time-intensity curve is narrower,indicating a rapid wash-in and wash-out of contrast agents.Therefore,DPI is able to estimate the blood volume in certain ROI because of its positive corre-lation with the intensity of contrast agents.On the other hand,MVD and VEGF are used as references for synovial angio-genesis.Thereby ,DPI correlates to MVD and VEGF .AUC is an indicator of volume of distribution (V d ),blood ?ow ,and velocity .Given certain microbubble volume,V d ,and equip-ment settings,AUC values are proportional to blood volume.Slope rate of A indicates changes in velocity and ?ow of micro-bubbles in certain ROI over time.In the case of active synovial in?ammation and increased angiogenesis,velocity and ?ow of microbubbles are elevated,thus,the values of DPI,AUC,and A can be indicators to represent blood ?ow and vascularity in synovial pannus (25–32).

Previous studies showed that quantitative parameters of contrast-enhanced sonography could be interfered by micro-bubble volume,type,tissue depth,and so on.T o eliminate these weaknesses,we attempted to control the experimental settings using same scanner and software with consistent parameter settings throughout the procedure.In addition,quantitative parameters may also be interfered by breathing movement when sonography is applied for liver or kidney scanning.However,this interference was avoided in the exam-ination of the joints in our study.Thus,parameters obtained in our study were relatively reliable for clinical reference.

There are some limitations in our study.First,the ROIs were set in the areas where the most prominent enhancement observed,which may not represent entire pannus vascularity.Because the inconsistency of area and depth of ROI may impair the reliability of parameter values,selected sampling error could exist in the present study.Second,the

quantitative

Figure 5.(continued ).

JIANG ET AL Academic Radiology,Vol 18,No 3,March 2011

366

measurement was obtained from the two-dimensional ultra-sound imaging,which cannot account for the entire in?amed synovial tissue.Thus,errors may occur when compared with histopathologic ?ndings.Further studiers with large samples are needed.

In conclusion,contrast-enhanced sonography can effectively image the neovascularities of synovial pannus in vivo.The TICs derived from real-time contrast-enhanced sonography enable quanti?cation of angiogenesis in synovial pannus.Parameters of TIC (ie,A,DPI,and AUC)were positively correlated to measurements of MVD and VEGF .Contrast-enhanced gray-scale sonography with TIC measurement could provide reliable method for noninvasive quantitative assessment of synovial pan-nus angiogenesis of arthritis,which could assess disease activity and response to therapy in clinical settings.

REFERENCES

1.Emery P,Gabay C,Kraan M,et al.Evidence-based review of biologic markers as indicators of disease progression and remission in rheumatoid arthritis.Rheumatol Int 2007;27:793–806.

2.Bodolay E,Koch AE,Kim J,et al.Angiogenesis and chemokines in rheumatoid arthritis and other systemic in?ammatory rheumatic diseases.J Cell Mol Med 2002;6:357–367.

3.Schmitt-Sody M,Landes J,Zysk SP,et al.Quantitative assessment of angiogenesis in murine antigen-induced arthritis by intravital ?uorescence microscopy.J Vasc Res 2003;40:460–466.

4.Szekanecz Z,Besenyei T,Paragh G,et al.Angiogenesis in rheumatoid arthritis.Autoimmunity 2009;42:563–573.

5.Taylor PC.Serum vascular markers and vascular imaging in assessment of rheumatoid arthritis disease activity and response to therapy.Rheuma-tology (Oxford)2005;44:721–728.

6.Boutry N,Morel M,Flipo RM,et al.Early rheumatoid arthritis:a review of MRI and sonographic ?ndings.Am J Roentgenol 2007;189:1502–1509.

7.Schueller-Weidekamm C,Krestan C,Schueller G,et al.Power Doppler sonography and pulse-inversion harmonic imaging in evaluation of rheu-matoid arthritis synovitis.Am J Roentgenol 2007;188:504–50

8.

8.Stone M,Bergin D,Whelan B,et al.Power Doppler ultrasound assessment of rheumatoid hand synovitis.J Rheumatol 2001;28:1979–1982.

9.Okura T,Marutsuka K,Hamada H,et al.Therapeutic ef?cacy of intra-articular adrenomedullin injection in antigen-induced arthritis in rabbits.Arthritis Res Ther 2008;10:R133.

10.Kristensen KD,Stoustrup P,K €u

seler A,et al.Quantitative histological changes of repeated antigen-induced arthritis in the temporomandibular joints of rabbits treated with intra-articular corticosteroid.J Oral Pathol Med 2008;37:437–444.

11.Appel H,Loddenkemper C,Miossec P.Rheumatoid arthritis and anky-losing spondylitis pathology of acute in?ammation.Clin Exp Rheumatol 2009;

27:S15–S19.

Figure 5.(continued ).

Academic Radiology,Vol 18,No 3,March 2011CONTRAST-ENHANCED SONOGRAPHY ASSESSMENT OF SYNOVIAL ANGIOGENESIS

367

12.Choi ST,Kim JH,Seok JY,et al.Therapeutic effect of anti-vascular endothe-

lial growth factor receptor I antibody in the established collagen-induced arthritis mouse model.Clin Rheumatol2009;28:333–337.

13.Szekanecz Z,Besenyei T,Szentp e tery A,et al.Angiogenesis and vas-

culogenesis in rheumatoid arthritis.Curr Opin Rheumatol2010;22: 299–306.

14.Mousa SA,Mousa SS.Current status of vascular endothelial growth factor

inhibition in age-related macular degeneration.BioDrugs2010;24: 183–194.

15.Szekanecz Z,Besenyei T,Paragh G,et al.New insights in synovial angio-

genesis.Joint Bone Spine2010;77:13–19.

16.Taylor PC.VEGF and imaging of vessels in rheumatoid arthritis.Arthritis

Res2002;4:S99–S107.

17.Schmidt WA,V€o lker L,Zacher J,et al.Colour Doppler ultrasonography to

detect pannus in knee joint synovitis.Clin Exp Rheumatol2000;18: 439–444.

18.Forsberg F,Ro RJ,Potoczek M,et al.Assessment of angiogenesis:

implications for ultrasound imaging.Ultrasonics2004;42:325–330.

19.Doria AS,Kiss MH,Lotito AP,et al.Juvenile rheumatoid arthritis of the

knee:evaluation with contrast-enhanced color Doppler ultrasound.

Pediatr Radiol2001;31:524–531.

20.Tsubaki T,Arita N,Kawakami T,et al.Characterization of histopathology

and gene-expression pro?les of synovitis in early rheumatoid arthritis using targeted biopsy specimens.Arthritis Res Ther2005;7:R825–R836.

21.Carotti M,Salaf?F,Manganelli P,et al.Power Doppler sonography in the

assessment of synovial tissue of the knee joint in rheumatoid arthritis:

a preliminary experience.Ann Rheum Dis2002;61:877–882.

22.Kersting S,Konopke R,Kersting F,et al.Quantitative perfusion analysis of

transabdominal contrast-enhanced ultrasonography of pancreatic masses and carcinomas.Gastroenterology2009;137:1903–1911.23.Krix M,Krakowski-Roosen H,Kauczor HU,et al.Real-time contrast-

enhanced ultrasound for the assessment of perfusion dynamics in skeletal muscle.Ultrasound Med Biol2009;35:1587–1595.

24.Ellegaard K,Torp-Pedersen S,Lund H,et al.Quanti?cation of colour

Doppler activity in the wrist in patients with rheumatoid arthritis—the reli-ability of different methods for image selection and evaluation.Ultraschall Med2008;29:393–398.

25.Cyteval C.Doppler ultrasonography and dynamic magnetic resonance

imaging for assessment of synovitis in the hand and wrist of patients with rheumatoid arthritis.Semin Musculoskelet Radiol2009;13:66–73.

26.Platzgummer H,Schueller G,Grisar J,et al.Quanti?cation of synovitis in

rheumatoid arthritis:do we really need quantitative measurement of contrast-enhanced ultrasound?Eur J Radiol2009;71:237–241.

27.De Zordo T,Mlekusch SP,Feuchtner GM,et al.Value of contrast-enhanced

ultrasound in rheumatoid arthritis.Eur J Radiol2007;64:222–230.

28.Chen LD,Xu HX,Xie XY,et al.Intrahepatic cholangiocarcinoma and

hepatocellular carcinoma:differential diagnosis with contrast-enhanced ultrasound.Eur Radiol2010;20:743–753.

29.Bertolotto M,Trincia E,Zappetti R,et al.Effect of Tadala?l on prostate

haemodynamics:preliminary evaluation with contrast-enhanced US.

Radiol Med2009;114:1106–1114.

30.Tang J,Yang JC,Luo Y,et al.Enhancement characteristics of benign and

malignant focal peripheral nodules in the peripheral zone of the prostate gland studied using contrast-enhanced transrectal ultrasound.Clin Radiol 2008;63:1086–1091.

31.Barnard S,Leen E,Cooke T,et al.A contrast-enhanced ultrasound study

of benign and malignant breast tissue.S Afr Med J2008;98:386–391. 32.Ignee A,Jedrejczyk M,Schuessler G,et al.Quantitative contrast enhanced

ultrasound of the liver for time intensity curves-Reliability and potential sources of errors.Eur J Radiol2010;73:153–158.

JIANG ET AL Academic Radiology,Vol18,No3,March2011 368

人教版九年级全册英语重点语法知识点复习提纲

人教版九年级全册英语重点语法知识点复习提纲 一. 介词by的用法(Unit-1重点语法) 1. 意为“在……旁”,“靠近”。 Some are singing and dancing under a big tree. Some are drawing by the lake. 有的在大树下唱歌跳舞。有的在湖边画画儿。 2. 意为“不迟于”,“到……时为止”。 Your son will be all right by supper time. 你的儿子在晚饭前会好的。 How many English songs had you learned by the end of last term? 到上个学期末你们已经学了多少首英语歌曲? 3. 表示方法、手段,可译作“靠”、“用”、“凭借”、“通过”、“乘坐”等。 The monkey was hanging from the tree by his tail and laughing. 猴子用尾巴吊在树上哈哈大笑。 The boy’s father was so thankful that he taught Edison how to send messages by railway telegraph. 孩子的父亲是那么的感激,于是他教爱迪生怎样通过铁路电报来传达信息。 4. 表示“逐个”,“逐批”的意思。 One by one they went past the table in the dark. 他们一个一个得在黑暗中经过这张桌子。 5. 表示“根据”,“按照”的意思。 What time is it by your watch? 你的表几点了? 6. 和take , hold等动词连用,说明接触身体的某一部分。 I took him by the hand. 我拉住了他的手。

人教版初中英语中考英语语法总结

中考英语语法总结 一、祈使句结构 1 祈使句结构 祈使句用以表达命令,要求,请求,劝告等。 1)祈使句有两种类型,一种是以动词原形开头,在动词原形之前加do (但只限于省略第二人称主语的句子)。 Take this seat. Do be careful. 否定结构: Don't move. Don't be late. 2)第二种祈使句以let开头。 Let 的反意疑问句 a. Let's 包括说话者 Let's have another try,shall we / shan't we = Shall we have another try b. Let us 不包括说话者 Let us have another try,will you / won't you = Will you please let us have another try

否定结构: Let's not talk of that matter. Let us not talk of that matter. 二、感叹句结构 感叹句结构 感叹句通常有what, how引导,表示赞美、惊叹、喜悦、等感情。 what修饰名词,how 修饰形容词,副词或动词,感叹句结构主要有以下几种: 掌握它的搭配,即掌握了感叹句的重点。 How +形容词+ a +名词+ 陈述语序 How+形容词或副词+ 陈述语序 What +名词+ 陈述语序 What+a+形容词+名词+ 陈述语序 What+ 形容词+复数名词+ 陈述语序 What+ 形容词+不可数名词+ 陈述语序 How clever a boy he is! How lovely the baby is! What noise they are making! What a clever boy he is!

初三英语语法知识点

1) leave的用法 1.“leave+地点”表示“离开某地”。例如: When did you leave Shanghai? 你什么时候离开上海的? 2.“leave for+地点”表示“动身去某地”。例如: Next Friday, Alice is leaving for London. 下周五,爱丽斯要去伦敦了。 3.“leave+地点+for+地点”表示“离开某地去某地”。例如:Why are you leaving Shanghai for Beijing? 你为什么要离开上海去北京? 2) 情态动词should“应该”学会使用

should作为情态动词用,常常表示意外、惊奇、不能理解等,有“竟会”的意思,例如: How should I know? 我怎么知道? Why should you be so late today? 你今天为什么来得这么晚? should有时表示应当做或发生的事,例如: We should help each other.我们应当互相帮助。 我们在使用时要注意以下几点: 1. 用于表示“应该”或“不应该”的概念。此时常指长辈教导或责备晚辈。例如: You should be here with clean hands. 你应该把手洗干净了再来。 2. 用于提出意见劝导别人。例如: You should go to the doctor if you feel ill. 如果你感觉不舒服,你最好去看医生。

3. 用于表示可能性。should的这一用法是考试中常常出现的考点之一。例如: We should arrive by supper time. 我们在晚饭前就能到了。 She should be here any moment. 她随时都可能来。 3) What...? 与Which...? 1. what 与which 都是疑问代词,都可以指人或事物,但是what仅用来询问职业。如: What is your father? 你父亲是干什么的? 该句相当于: What does your father do? What is your father's job? Which 指代的是特定范围内的某一个人。如:

(完整版)人教版初中英语语法完整总结

1 . (see 、hear 、notice 、find 、feel 、listen 从句感觉/对什么有信心,自信 to 、look at ( 感官动词)+(sb. )+do sth. eg : I am/ feel confident of myspoken English. eg:I like watching monkeys jump. I feel that I can pass the test . 2 . (比较级and 比较级)表示越来越怎么样18. be + doing 表:1现在进行时2将来时 eg:the more the more 越来越多19 . be able to (+ v 原) = can (+ v 原)能够?? 3. a piece of cake =easy 小菜一碟(容易)eg : She is able to sing .= She can sing. 4 . agree with sb赞成某人20. be able to do sth. 能够干什么 5 . all kinds of 各种各样a kind of 一样e g :she is able to sing . 6 . all over the world = the whole world 整个21. be afraid to do (of sth 恐惧,害怕??世界eg : I'm afraed to go out at night . 7. along with 同??一道,伴随??I'm afraid of dog. eg : I will go along with you. 我将和你一起去22. be allowed to do 被允许做什么 The students planted trees along with their eg: I'm allowed to watch TV. 我被允许看电视teachers. 学生同老师们一起种树I should be allowed to watch TV. 我应该被允 8. as soon as 一怎么样就怎么样 许看电视 9 . as you can see 你是知道的(正如你所见)23. be angry with sb 生某人的气 10 . ask for ??求助向?要?(直接接想要的东e g : Don't be angry with me. 西)24. be angry with(at) sb for doing sth 12. ask sb to do sth询问某人某事 为什么而生某人的气 ask sb not to do 叫某人不要做某事25. be as ?原级?as 和什么一样 13 . at the age of 在??岁时eg : She is as tall as me. 她和我一样高 eg :I amsixteen. = I am at the age of sixteen . 26. be ashamed to 14. at the beginning of ????的起初;??27. be away from远离 的开始28. be away from 从??离开 15. at the end of + 地点/+时间最后;尽头;末29. be bad for对什么有害 尾eg : Reading books in the sun is bad for your eg : At the end of the day eyes. 在太阳下看书对你的眼睛不好 16. at this time of year 在每年的这个时候30. be born 出生于 17. be /feel confident of sth /that clause + 31. be busy doing sth 忙于做什么事

场景设计方法

设计测试用例方法--场景设计方法 1方法简介 1.1定义 通过运用场景来对系统的功能点或业务流程的描述,从而提高测试效果。场景法一般包含基本流和备用流,从一个流程开始,通过描述经过的路径来确定的过程,经过遍历所有的基本流和备用流来完成整个场景。 1.2产生背景 为什么场景法能如此清晰的描述整个事件因为,现在的系统基本上都是由事件来触发控制流程的。如:我们申请一个项目,需先提交审批单据,再由部门经理审批,审核通过后由总经理来最终审批,如果部门经理审核不通过,就直接退回。每个事件触发时的情景便形成了场景。而同一事件不同的触发顺序和处理结果形成事件流。这一系列的过程我们利用场景法可以清晰的描述清楚。

1.3实例图 在这个图中,有一个基本流和四个备选流。 每个经过用例的可能路径,可以确定不同的用例场景。从基本流开始,再将基本流和备选流结合起来,可以确定以下用例场景:

场景 1 基本流 场景 2 基本流备选流1 场景 3 基本流备选流 1 备选流2 场景 4 基本流备选流3 场景 5 基本流备选流 3 备选流1 场景 6 基本流备选流 3 备选流 1 备选流2 场景7 基本流备选流4 场景8 基本流备选流 3 备选流4 从上面的实例我们就可以了解场景是如何利用基本流和备用流来确定的。 基本流:采用直黑线表示,是经过用例的最简单的路径(无任何差错,程序从开始直接执行到结束) 备选流:采用不同颜色表示,一个备选流可能从基本流开始,在某个特定条件下执行,然后重新加入基本流中,也可以起源于另一个备选流,或终止用例,不在加入到基本流中;(各种错误情况)

1.4基本设计步骤 1.根据说明,描述出程序的基本流及各 项备选流 2.根据基本流和各项备选流生成不同的 场景 3.对每一个场景生成相应的测试用例 4.对生成的所有测试用例重新复审,去 掉多余的测试用例,测试用例确定后,对每一个测试用例确定测试数据值 2实战演习 2.1ATM机问题 下图所示是ATM例子的流程示意图。

九年级英语全册所有必考语法点都在这里了,初三都在看!

一. 介词by的用法 1. 意为“在……旁”,“靠近”。 Some are singing and dancing under a big tree. Some are drawing by the lake. 有的在大树下唱歌跳舞。有的在湖边画画儿。 2. 意为“不迟于”,“到……时为止”。 Your son will be all right by supper time. 你的儿子在晚饭前会好的。 How many English songs had you learned by the end of last term? 到上个学期末你们已经学了多少首英语歌曲? 3. 表示方法、手段,可译作“靠”、“用”、“凭借”、“通过”、“乘坐”等。 The monkey was hanging from the tree by his tail and laughing. 猴子用尾巴吊在树上哈哈大笑。 The boy’s father was so thankful that he taught Edison how to send messages by railway telegraph. 孩子的父亲是那么的感激,于是他教爱迪生怎样通过铁路电报来传达信息。 4. 表示“逐个”,“逐批”的意思。 One by>他们一个一个得在黑暗中经过这张桌子。 5. 表示“根据”,“按照”的意思。 What time is it by your watch? 你的表几点了? 6. 和take , hold等动词连用,说明接触身体的某一部分。 I took him by the hand. 我拉住了他的手。 7. 用于被动句中,表示行为主体,常译作“被”、“由”等。

人教版英语九年级语法知识点

1. by + doing 通过……方式如:by studying with a group by 还可以表示:"在…旁","靠近","在…期间"、"用,""经过","乘车"等如:I live by the river. I have to go back by ten o'clock. The thief entered the room by the window. The student went to park by bus. 2. talk about 谈论,议论,讨论 如:The students often talk about movie after class. 学生们常常在课后讨论电影。talk to sb. === talk with sb. 与某人说话 3. 提建议的句子: ①What/ how about +doing sth.? 如:What/ How about going shopping? ②Why don't you + do sth.? 如:Why don't you go shopping? ③Why not + do sth. ? 如:Why not go shopping? ④Let's + do sth. 如:Let's go shopping ⑤Shall we/ I + do sth.? 如:Shall we/ I go shopping? 4. a lot 许多常用于句末如:I eat a lot. 我吃了许多。 5. too…to 太…而不能常用的句型too+adj./adv. + to do sth. 如:I'm too tired to say anything. 我太累了,什么都不想说。 6. aloud, loud与loudly的用法三个词都与"大声"或"响亮"有关。 ①aloud是副词,重点在出声能让人听见,但声音不一定很大, 常用在读书或说话上。通常放在动词之后。aloud没有比较级 形式。如: He read the story aloud to his son.他朗读那篇故事给他儿子听。 ②loud可作形容词或副词。用作副词时,常与speak, talk, laugh等动词连用,多用于比较级,须放在动词之后。如: She told us to speak a little louder. 她让我们说大声一点。 ③loudly是副词,与loud同义,有时两者可替换使用,但往往 含有令人讨厌或打扰别人的意思,可位于动词之前或之后。 如: He does not talk loudly or laugh loudly in public. 他不当众大声谈笑。 7. not …at all 一点也不根本不如: I like milk very much. I don't like coffee at all. 我非常喜欢牛奶。我一点也不喜欢咖啡。 not经常可以和助动词结合在一起,at all 则放在句尾 8. be / get excited about sth.=== be / get excited about doing sth. === be excited to do sth. 对…感兴奋如: I am / get excited about going to Beijing.=== I am excited to go to Beijing. 我对去北京感到兴奋。 9. ①end up doing sth 终止做某事,结束做某事如: The party ended up singing. 晚会以唱歌而结束。 ②end up with sth. 以…结束如: The party ended up with her singing. 晚会以她的歌唱而告终。 10. first of all 首先. to begin with 一开始later on 后来、随 11. also 也、而且(用于肯定句)常在句子的中间 either 也(用于否定句)常在句末 too 也(用于肯定句) 常在句末 12. make mistakes 犯错如:I often make mistakes. 我经常犯错。

初三英语语法知识点归纳

初中英语语法速记口诀大全 很多同学认为语法枯燥难学,其实只要用心并采用适当的学习方法,我们就可以愉快地学会英语,掌握语法规则。笔者根据有关书目和多年教学经验,搜集、组编了以下语法口诀,希望对即将参加中考的同学们有所帮助。 一、冠词基本用法 【速记口诀】 名词是秃子,常要戴帽子, 可数名词单,须用a或an, 辅音前用a,an在元音前, 若为特指时,则须用定冠, 复数不可数,泛指the不见, 碰到代词时,冠词均不现。 【妙语诠释】冠词是中考必考的语法知识之一,也是中考考查的主要对象。以上口诀包括的意思有:①名词在一般情况下不单用,常常要和冠词连用;②表示不确指的可数名词单数前要用不定冠词a或an,确指时要用定冠词the;③如复数名词表示泛指,名词前有this,these,my,some等时就不用冠词。 二、名词单数变复数规则 【速记口诀】 单数变复数,规则要记住, 一般加s,特殊有几处: 末尾字母o,大多加s, 两人有两菜,es不离口, 词尾f、fe,s前有v和e; 没有规则词,必须单独记。 【妙语诠释】①大部分单数可数名词变为复数要加s,但如果单词以/t蘩/、/蘩/、/s/发音结尾(也就是单词如果以ch,sh,s,x等结尾),则一般加es;②以o结尾的单词除了两

人(negro,hero)两菜(tomato,potato) 加es外,其余一般加s;③以f或fe结尾的单词一般是把f,fe变为ve再加s;④英语中还有些单词没有规则,需要特殊记忆,如child—children,mouse—mice,deer—deer,sheep—sheep,Chinese—Chinese,ox—oxen,man—men,woman—women,foot—feet,tooth —teeth。 三、名词所有格用法 【速记口诀】 名词所有格,表物是“谁的”, 若为生命词,加“’s”即可行, 词尾有s,仅把逗号择; 并列名词后,各自和共有, 前者分别加,后者最后加; 若为无生命词,of所有格, 前后须倒置,此是硬规则。 【妙语诠释】①有生命的名词所有格一般加s,但如果名词以s结尾,则只加“’”;②并列名词所有格表示各自所有时,分别加“’s”,如果是共有,则只在最后名词加“’s”;③如果是无生命的名词则用of表示所有格,这里需要注意它们的顺序与汉语不同,A of B要翻译为B的A。 四、接不定式作宾语的动词 【速记口诀】 三个希望两答应,两个要求莫拒绝; 设法学会做决定,不要假装在选择。 【妙语诠释】三个希望两答应:hope,wish,want,agree,promise 两个要求莫拒绝:demand,ask,refuse 设法学会做决定:manage,learn,decide 不要假装在选择:petend,choose 五、接动名词作宾语的动词

动画场景设计课程标准

《动画场景设计》课程标准 一、课程定位 该课程是动漫制作技术专业的一门专业核心课程,是在多年教学改革的基础上,通过对数字媒体相关职业工作岗位进行充分调研和分析的基础上,借鉴先进的课程开发理念和基于工作过程的课程开发理论,进行重点建设与实施的学习领域课程。其目标是如何使用3ds max 制作高品质的室内外建筑效果图。按照软件功能以及实际应用进行划分,熟练运用3ds max软件设计出精品的室内场景和游戏场景;同时还将学习如何进行角色设计,其中以游戏角色设计、角色动画为主线进行教学,让学生能够独立制作出具有动画效果的游戏角色。 二、课程教学目标 1、知识目标 (1)、掌握室内场景和游戏场景的设计要求; (2)、掌握第三方的渲染软件的基本使用方法; (3)、掌握第三方角色创建方法; (4)、数量应用三维动画软件创建出较为真实的室内场景及游戏场景; (5)、能够应用三维动画掌握常见角色的创建方法 2、技能目标 (1)、掌握游戏场景的创建方法; (2)、掌握多种不同游戏场景、道具模型的创建方法; (3)、掌握VRAY等多种不同渲染器的使用; (4)、掌握Q版角色的模型创建方法; (5)、能熟练应用第三方软件创建角色动画。 3、素质目标 (1)、培养良好的思想品德、心理素质 (2)、培养良好的职业道德,包括爱岗敬业、诚实守信、遵守相关的法律法规等;

(3)、培养良好的团队协作、协调人际关系的能力; (4)、培养对新知识、新技能的学习能力与创新能力。 三、课程设计思路 该课程是依据数动漫制作技术专业工作任务与职业能力分析中的“三维场景制作及角色动画”工作项目设置的。其总体设计思路是,打破以知识传授为主要特征的传统学科课程模式,转变为基于工作过程的教学模式,以完整的室内及动画场景的工作任务为对象,组织学生通过完成这些工作任务来学习相关的知识、培养相应的职业能力。 课程内容突出对学生职业能力的训练,相关理论知识均与所要完成的工作任务有密切联系,并充分考虑了高等职业教育对理论知识学习的需要,融合相关职业资格证书对知识、技能和态度的要求。课程的教学过程要通过校企合作,校内实训基地建设等多种途径,采取工学结合等形式,充分开发学习资源,给学生提供丰富的实践机会。 教学效果评价采取过程评价与结果评价相结合的方式,通过理论与实践相结合,重点评价学生的职业能力。 四、教学内容安排及学时分配 详见表一 五、教学实施方案设计 详见表二 六、教学实施条件 1、教师任职条件 (1)、要求承担本专业教学任务的老师要熟悉和了解本专业的培养目标、教学计划、整个课程体系; (2)、要求老师了解整个课程体系中各课程的前后关系;

人教版九年级英语各单元知识点总结

九年级英语全册各单元知识点总结 Unit 1 How can we become good learners? 一、短语: 1.have conversation with sb. 同某人谈话 2.connect …with… 把…和…连接/联系起来 3.the secret to… ……的秘诀 4.be afraid of doing sth./to do sth. 害怕做某事 5.look up 查阅 6.repeat out loud 大声跟读 7.make mistakes in 在……方面犯错误8.get bored 感到厌烦 9.be stressed out 焦虑不安的10.pay attention to 注意;关注 11.depend on 取决于;依靠12.the ability to do sth. 做某事的能力 二、知识点: 1. by + doing:通过……方式(by是介词,后面要跟动名词,也就是动词的ing形式); 2. a lot:许多,常用于句末; 3. aloud, loud与loudly的用法,三个词都与“大声”或“响亮”有关。 ①aloud是副词,通常放在动词之后。 ①loud可作形容词或副词。用作副词时,常与speak, talk, laugh等动词连用,多用于比较级, 须放在动词之后。 ①loudly是副词,与loud同义,有时两者可替换使用,可位于动词之前或之后。 4. not …at all:一点也不,根本不,not经常可以和助动词结合在一起,at all 则放在句尾; 5. be / get excited about sth.:对…感到兴奋; 6. end up doing sth:终止/结束做某事;end up with sth.:以…结束; 7. first of all:首先(这个短语可用在作文中,使得文章有层次); 8. make mistakes:犯错make a mistake 犯一个错误; 9. laugh at sb.:笑话;取笑(某人)(常见短语) 10. take notes:做笔记/记录; 11. native speaker 说本国语的人; 12. make up:组成、构成; 13. deal with:处理、应付; 14. perhaps = maybe:也许; 15. go by:(时间)过去; 16.each other:彼此; 17.regard… as … :把…看作为…; 18.change… into…:将…变为…; 19. with the help of sb. = with one's help 在某人的帮助下(注意介词of和with,容易出题) 20. compare … to …:把…比作… compare with 拿…和…作比较; 21. instead:代替,用在句末,副词; instead of sth / doing sth:代替,而不是(这个地方考的较多的就是instead of doing sth,也就是说如果of后面跟动词时,要用动名词形式,也就是动词的ing形式) 22.Shall we/ I + do sth.? 我们/我…好吗? 23. too…to:太…而不能,常用的句型是too+形容词/副词+ to do sth.

人教版初中英语语法完整总结(最新最全)

1 .(see 、hear 、notice 、find 、feel 、listen to 、 look at (感官动词)+(sb.)+do sth. eg:I like watching monkeys jump. 2 .(比较级 and 比较级)表示越来越怎么样eg:the more the more 越来越多 3. a piece of cake =easy 小菜一碟(容易) 4 .agree with sb 赞成某人 5 .all kinds of 各种各样 a kind of 一样 6 .all over the world = the whole world 整个世界 7. along with同……一道,伴随…… eg : I will go along with you.我将和你一起去The students planted trees along with their teachers. 学生同老师们一起种树 8. as soon as 一怎么样就怎么样 9 .as you can see 你是知道的(正如你所见) 10 .ask for ……求助向…要…(直接接想要的东西) 12. ask sb to do sth 询问某人某事 ask sb not to do 叫某人不要做某事 13 .at the age of 在……岁时 eg:I am sixteen. = I am at the age of sixteen . 14.at the beginning of …… ……的起初;……的开始 15. at the end of +地点/+时间最后;尽头;末尾 eg : At the end of the day 16.at this time of year 在每年的这个时候 17. be /feel confident of sth /that clause +从句感觉/对什么有信心,自信 eg : I am / feel confident of my spoken English. I feel that I can pass the test . 18. be + doing 表:1 现在进行时 2 将来时 19 .be able to (+ v 原) = can (+ v 原)能够…… eg : She is able to sing .= She can sing. 20. be able to do sth. 能够干什么 eg :she is able to sing . 21. be afraid to do (of sth 恐惧,害怕…… eg : I'm afraed to go out at night . I'm afraid of dog. 22. be allowed to do 被允许做什么 eg: I'm allowed to watch TV. 我被允许看电视 I should be allowed to watch TV. 我应该被允许看电视 23. be angry with sb 生某人的气 eg : Don't be angry with me. 24. be angry with(at) sb for doing sth 为什么而生某人的气 25.be as…原级…as 和什么一样 eg : She is as tall as me. 她和我一样高 26.be ashamed to 27.be away from 远离 28. be away from 从……离开 29. be bad for 对什么有害 eg : Reading books in the sun is bad for your eyes. 在太阳下看书对你的眼睛不好 30. be born 出生于 31.be busy doing sth 忙于做什么事

场景设计教案

教师课时授课计划 教师姓名:授课班级: 授课课时:2 课程名称:二维动画场景设计第 6讲教学循环号:1-6 详细教学过程附后

一、教学目标 掌握动画场景设计图的制作技法。 二、二维动画设计与制作软件工具介绍 在二维动画设计与制作中,除了传统的手绘工具之外,现在更为常用的是各种计算机辅助软件,利用各种软件工具,可以很大程度上节省动画影片制作成本,提高工作效率。 当今主流的动画制作软件按大的范围分,分为图像处理软件、动画制作软件与后期合成软件。在二维动画场景的制作中,主要是利用图像处理软件进行线稿绘制、上色以及特效处理。 1.PHOTOSHOP Adobe Photoshop是公认的最好的通用平面美术设计软件。由Adobe公司开发设计。其用户界面易懂,功能完善,性能稳定,所以,在几乎所有的广告、出版、软件公司,Photosho p都是首选的平面工具。 在动画制作行业,传统的动画制作方法,比如说手工描线,在赛璐璐片上上色等处理工序,基本上都已被电脑操作所取代,Adobe Photoshop具有很强的图形处理能力,将线稿扫描进电脑后,可在Photoshop中对线稿进行优化,然后利用强大的画笔功能与图层功能对线稿进行着色,从而完成动画场景的绘制。 (1) Photoshop的特点: ·丰富多样的Brush(画笔)工具可以完全模拟现实的绘画工具

·快速高效的选择工具可以快速锁定目标 ·Layer(图层)的应用使复杂的图像处理轻松有序 ·丰富的Layer Style(图层样式)快速给字体或图形添加效果 ·矢量图形操作简单 ·完善的文字编辑功能 ·实用而精致的Filter(滤镜)为设计增添更多的特殊效果 (2) Photoshop界面介绍 作为图形处理的专业软件之一, photoshop具有Adobe公司一贯的软件设计风格,在界面上,菜单上等都具有相当高的人性化设计在其中。而做为Adobe公司的产品之一,也保持了与其他软件交叉使用的方便及快捷。 菜单栏工具信息栏控制面板 文档窗口 1.菜单栏:集成了在图像处理过程中所用到的各种命令,以及包含了在图形处理过程中所用到各种文件存储,打开,软件设置,面板的调换等。

初三英语语法知识点总结大全

初三英语语法知识点总结大全 导读:我根据大家的需要整理了一份关于《初三英语语法知识点总结大全》的内容,具体内容:1 agree with sb 赞成某人2 all kinds of 各种各样 a kind of 一样3 a piece of cake =easy 小菜一碟(... 1 agree with sb 赞成某人 2 all kinds of 各种各样 a kind of 一样 3 a piece of cake =easy 小菜一碟(容易) 4 (see 、hear 、notice 、find 、feel 、listen to 、 look at (感官动词)+do eg:I like watching monkeys jump 5(比较级 and 比较级) 表示越来越怎么样 6 all over the world = the whole world 整个世界 7 along with同......一道,伴随...... eg : I will go along with you我将和你一起去 the students planted trees along with their teachers 学生同老师们一起种树 8 As soon as 一怎么样就怎么样 9 as you can see 你是知道的 10 ask for ......求助向...要...(直接接想要的东西) eg : ask you for my book 11 ask sb for sth 向某人什么 12 ask sb to do sth 询问某人某事 ask sb not to do 叫某人不要做

完整版人教版初中英语语法总复习

初中英语语法总复习 一、时态一般现在时 定义:经常、反复发生的动作或行为及现在的某种状况。动词用原形(单三人称动词加s / es) (问句和否定句借用助词do / does) 一般过去时 定义:过去某个时间里发生的动作或状态;过去习惯性、经常性的动作、行为。动词用过去式 (问句和否定句借用助词did) 现在进行时 定义:表示现阶段或说话时正在进行的动作及行为。 am +动词-ing is +动词-ing are +动词-ing 过去进行时定义:表示过去某段时间或某一时刻正在发生或进行的行为或动作。 was +动词-ing were +动词-ing 一般将来时定义:以过去某个时间为标准,在此以前发生的动作或行为,或在过去某动作之前完成的行为,即“过去的过去”。 (1)will + 动词原形 (2)am +going to+动词原形 Is +going to+动词原形 are +going to+动词原形 过去将来时定义:立足于过去某一时刻,从过去看将来,常用于宾语从句中。 (1)would + 动词原形 (2)was +going to+动词原形 were +going to+动词原形现在完成时 定义:过去发生或已经完成的动作对现在造成的影响或结果,或从过去已经开始,持续到现在的动作或状态。 have +过去分词 has +过去分词过去完成时 定义:以过去某个时间为标准,在此以前发生的动作或行为,或在过去某动作之前完成的行为,即“过去的过去”。 had +过去分词 1. 不定式定义:由to+动词原形构成。不定式是一种非限定性动词。而非限定动词是指那些在句中不能单独充当谓语的动词,可分为不定式,动名词,现在分词和过去分词。 2.用途:在句中不能作谓语。它具有动词的性质,本身可以带宾语和状语。 【动词不定式】 1.定义:动词 + 不定式 2.用途:动词不定式在句中可以作句子任何成分。动词不定式的被动形式除了一般形式外还有其完成式和进行式。[编辑本段][动词不定式的时态、语态] 动词不定式可以作以上各种成分,但它毕竟是动词,所以有动词的属性 动词不定式及其短语还可以有自己的宾语、状语,虽然动词不定式在语法上没有表面上的直接主语,但它表达的意义是动作,这一动作一定由使动者发出。这一使动者我们称之为逻辑主语,其形式如下: 主动形式被动形式一般式(not) to make (not) to be made 完成式(not) to have made (not) to have been made 进行式(not) to be making 完成进行式(not) to have been making (1)语态 如果动词不定式的逻辑主语是这个不定式所表示的动作的承受者,不定式一般要用被动语态形式。如: It's a great honour to be invited to Mary's birthday party.(不定式作主语) It was impossible for lost time to be made up.(不定式作主语) I wish to be sent to work in the country.(不定式作宾语) Can you tell me which is the car to be repaired?(不定式作定语) He went to the hospital to be examined.(不定式作状语) 在There be结构中,修饰主语的不定式可用被动,也可用主动。如:There are still many things to t ake care of (to be taken care of).但有时两种形式表达的意思不同,如:These is nothing to do now.( We have nothing to do now.) There is nothing to be

场景设计的原则

:《动画场景设计》由国际权威动漫人士策划,结合东、西方经典动画的创作原则、制作规律及表现技巧,全方位解析动画绘制技巧,是国内外顶尖动画师几十年制作经验和表现技巧的系统总结。《动画场景设计》凝结作者多年从业经验,深入讲解场景设计的方法,主要内容包括透视原理、构图法则、基础绘画技巧、辅助练习、主观镜头、超广角镜头、黑白色块风格、线与图案相结合的风格、随意线条及涂鸦风格、中国画风格、色彩概念设计、道具配件和自然现象设计等方面知识以及50 余个教学实例。 循序渐进的讲解方式、实训式的强化训练,使学习者能够掌握较强的实践能力,能够胜任影视、动画、游戏等相关行业职位,具备较强的就业竞争力。 《动画场景设计》可作为动画、游戏专业学生的教材,还可以作为数字娱乐、动漫游戏等专业人士的参考用书,值得广大动漫爱好者收藏。 作者简介: 武立杰,20 世纪80 年代起便投身动画设计与制作行业,在20 多年的从业时间里,参与设计与 制作欧美、日本、台湾等地百余部各种风格的动画影片,特长在动画前期美术设计方向。 现任吉林动画学院动画前期美术设计专业教师吉林动画学院动漫学院副院长 曾获吉林省优秀教师并担当中国学院奖专家委员会委员中国学院奖终审评委(三届)中国数字设计委员会委员吉林省高校视觉艺术大赛评委参与设计与制作及出版的部分作品 1.动画作品 美国迪士尼动画公司电视动画片集《飞旋的传说》美国迪士尼动画公司电视动画片集《甘美熊》德国动画系列片集《老鼠游世界》 英国动画电视系列片集《靴人的故事》法国水彩系列动画片集《猫的故事》美国动画系列片集《小恐龙》西班牙动画片《超级模特》法国动画系列片《WOMBAT CITY 》日本动画系列片《双生子》 2.出版作品 香港连环漫画《鬼眼》、《天战》(彩搞设计)中国连环画出版社出版发行的彩色连环画《海尔兄弟》(封面设计)《镜头设计稿基础教程》由吉林美术出版社出版发行 1 引言 动画影片中场景设计是动漫作品构成中重要的组成部分,场景设计是指动漫游戏中除角色造型以外的随着时间改变而变化的一切物的造型设计。好的场景设计可以提升动画影片的美感、强化渲染主题,它能够使动画影片的渲染效果更加饱满。恰当的场景设计更能为影视作品提升附加值,直接影响着整部作品的风格和艺术水平。 2 场景设计在动漫游戏中的作用 动画影片的主体是动画角色,场景就是围绕在角色周围,与角色有关系的所有 景物,即角色所处的生活场所,社会环境,自然环境及历史环境,甚至包括作为社会背景出现的群众角色,都是场景设计的范围。即除人物角色外的一切物的造型设计。它既不是单纯的环境艺术设计。单纯的环境艺术设计是一种空间样式的创造, 它也不是单独的背景描绘,而是依据影片的剧本,人物,特定的时间线索来进行的有高度创造性的艺术创作。形式追随功能,场景追随影片”这是场景设计的基本法则。 场景的设计对整部动画的设计风格,镜头画面,角色塑造,情绪氛围,社会空间, 物质空间都有很大的影响。场景设计还有可能影响到剧情发展,比如古代对建筑规模和建筑形制的规定都很严格,那么古装角色要根据自己的身份选择合适的建筑去居住和生活,活动范围也会受到限制,剧情要依照这些场景来展开。 场景设计不但影响着角色与剧情,而且还影响着影视动画的欣赏。动画片给观

【新整理】:人教版九年级英语全册知识点归纳

九年级英语全册知识点归纳及习题 Unit 1 How can we become good learners? 短语总结: 1. good learners 优秀的学习者 2. work with friends 和朋友一起学习 3. study for a test 备考 4.have conversations with 与……交谈 5.speaking skills 口语技巧 6.a little 有点儿 7.at first 起初起先8.the secret to......,.......的秘诀9.because of 因为10.as well 也 11.look up (在词典中等)查阅;抬头看12.so that 以便,为了 13.the meaning of ……的意思14.make mistakes 犯错误 15.talk to 交谈16.depend on 依靠依赖 17.in common 共有的18.pay attention to 注意关注19.connect ……with ……把……联系。20.for example 例如 21.think about 考虑22.even if 即使尽管纵容 23.look for 寻找24.worry about 担心担忧 25.make word cards 制作单词卡片26.ask the teacher for help 向老师求助 27.read aloud 大声读28.spoken english 英语口语 29.give a report 作报告30.word by word 一字一字地 31.so……that 如此……以至于32.fall in love with 爱上

相关主题
文本预览
相关文档 最新文档