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帕金森大鼠模型的影像特性

2024-07-29 来源:爱go旅游网
Mar.2010 Transactions of Nanjing University of Aeronautics&Astronautics Vo1.27 No.1 IMAGING CHARACTERISTICS oF RAT MoDELS oF PARKINSoN DISEASE Hu Guangxia ,Qian Zhiyu ,Sun Tao ,Yang Tianming。, Wang Wenhong ,Xie Jieru (1.College of Automation Engineering,NUAA,29 Yudao Street,Nanjing,210016,P.R.China; 2.Zhongda Hospital,Southeast University,Naniing,210009,P.R.China) Abstract:Imaging technologies are utilized to study the brain morphology and the functions of rat models of Parkinson disease(PD).Magnetic resonance imaging(MRI)and magnetic resonance angiography(MRA)are used to obtain morphological imaging data.Functional imaging data,such as the spectrum and blood flow changes are obtained by proton magnetic resonance spectroscopy( H-MRS)and CT perfusion(CTP).Results show that PD rat models have no characteristic morphological imaging abnormalities,hut exist regional cerebral blood flow (CBF)reductions and spectral changes in the striatum. Key words:medical imaging;brain morphology;Parkinson disease;magnetic resonance imaging;CT perfusion CLC number:R318;R445.2 Document code:A Article ID:1005—1120(201O)01—0039—06 INTRoDUCTIoN cerebral blood dissolved,and gl ucose metabolism can be obtained in non—invasive.A breakthrough Parkinson disease(PD)is a common neu— is expected for the early diagnosis of PD[。‘ . rodegenerative disease(the substantia nigra and Imaging technologies are utilized for the sys— substantia nigra—・striatal pathway degeneration in. tematic study on the brain morphology and func— duced extrapyramida1 disease),which is common tion changes of PD rat models.Firstly,rat mod— and frequently—occurring among elderly people, els are established.Then,rat brains of the three and seriously endangers human health.Current— groups are examined on MRI and magnetic reson— ly,the diagnosis of PD is mainly through symp— ahce angiography(MRA)to observe if there are toms and signs.However,it is subjective and can morphology and anatomy changes.Finally,pro— result in a certain degree of the misdiagnosis due to individua1 differences in patient clinical mani— ton magnetic resonance spectroscopy( H—MRS) and CT perfusion(CTP)are used to observe bi— festations and clinician Ievel of experience.More— lateral striatal energy metabolisms,biochemical over,once patients have obvious signs and symp— toms,the disease tends to be more severe actually changes,quantitative analysis of specific com— and treatments show less efficacy.So,it is par— pounds,CBF,and cerebral blood volume(CBV) ticularly urgent to find an early and objective di— of three groups of rats,thus providing research agnosis technology for PDl】J.In recent years。 bases for the diagnosis of pDE _4]. with the rapid development of new diagnosis tech— 1 METHoD nologies,particularly the progress of morphology and function imaging technologies such as mag— 1.1 Establishment of PD rat models netic resonance imaging(MRI)and computed to— Three-month—old 2l0—24O g sprague dawley mography(CT),parameters,such as the region— (SD)rats E。]are selected and divided into three al brain morphology,cerebral blood flow(CBF), groups:the model group(月一40),the sham— Foundation item:Supported by the National Natural Science Foundation of China(30671997) Received date:2009—04—1 1;revision received date:2009—07—09 E—mail:zhiyu@nuaa.edu.cn 40 Transactions of Naniing University of Aeronautics&Astronautics VoI.27 operated group(n一20)and the normal group ( 一20).Rats of the model group are single— low signal needle road and the skull of the punc— ture site appears circular high signal defect area (see Fig.1).The puncture road of the success PD rat model is exactly located in the substantia ni— gra.The low signal needle road is vertical to the point injected with 5 L 5 t ̄g/tA 6-hydroxy— dopamine(6一OHDA)containing 0.2%ascorbic acid saline on the right substantia nigra pars corn— pacta(SNc)to be mold.Rats of the sham—operat— rat brain in both sagittal and coronal planes. Moreover,the ending point of the needle is exact— ed group are injected with 5 I saline containing 0.2%aseorbic acidc引.Intraperitoneal injection with apomorphine(APO)(0.5 mg/kg)is adopt— lY located in SNc.The needle road of the failure PD rat modeI iS deviated from SNc。skewing for— ed to check the molding results of PD rat models. If the rat turns to the left side constantly and the rotating turns in 30 rain are larger than 210 laps, it is regarded as a successful PD rat model[ . Then,male and female rats of the three groups are bred in different cages.After three months, the molding results are verified again with the same method.Subsequently,rats are examined with MRI,MRA, H—MRS,CTP,light micro— scope,and electron microscope. 1.2 Imaging examinations Firstly,after some rats from each of the three groups are anesthetized,7.0 T Biospec small animal MRI from Germany Bruker company is used to do corona1 and sagittal T1WI,T2WI scans and MRA examinations of rat brains. Then,bilateral striatal H—MRS examinations are done to obtain spectral images,such as N—acetyl aspartate(NAA),choline compounds(Cho), and creatine(Cr)signals.After that,NAA/Cr and Cho/Cr ratios(compared with the integration area)are calculated.Next,somatom sensation 64一slice CT from SIEMENS is used to do bilateral striatal perfusion scans with iohexoI (350 mg/mI )as the contrast agent,which is injected at the same time with scanning.Finally,480 con— secutive axial images of rat brains are obtained and then dealt with to obtain the pseudo—color pictures and the specific quantitative values of CBF and CBV. 2 RESULTS AND ANALYSES 2.1 Results of MRI and MRA examinations T2一weighted images of the model and sham— operated groups of rats show the striatum and other parts of the brain have no significant changes except that the puncture area leaves a ward or backward in the sagittal plane and skew— ing inside or outside in the coronary plane(see Fig.2).MRA shows that the vascular structures of all rat brains are normal without the difference between left and right sides(see Fig.3). Fig.1 MRI of striatum of model and sham—operated rats 2.2 Results of H—MRS and CTP examinations H—MRS and CTP are used to detect the bi— lateral striatum of three group rats.Fig.4 shows the H—MRS spectra,where Fig.4(a)is the loca— tion map for the striatum;and Figs.4(b—e)show the spectra of the normal rat,the left and right sides of the sham—operated rat.the non—injected (1eft)side of the model rat,respectively.All of them reveal that the NAA peak is significantly higher than the Cr peak.Fig.4(f)shows the spectrum of the injected(right)side,revealing that NAA and Cr peaks are basically in the same leve1.Fig.5 shows the CTP pseudo—color pic— lures.Figs.5(a,b)show the CBF,CBV maps of the striatum of the model group rat,which indi— cate that the color of the injected side(arrow points)is darker than the non—injected side.It represents that the blood flow and the blood vol— ume of the injected side are lower than those of the non—injected side.Figs.5(c—d)show the CBF 42 Transactions of Nanjing University of Aeronautics&Astronautics V0I_27 sides of sham—operated and normal rats(P> er than those of the left side。bilateral sides of 0.05).For the Cho/Cr ratio,there is also no sig— sham—operated and normal rats(尸<0.05).No nificant statistical difference among three groups significant statistical difference exists among the of rats(P>0.05).CBF and CBV of the injected 1eft side of the model rat and the bilateral sides of (right)side of the model rat are considerably low— sham—operated and normal rats(P>0.05). Table 1 Statistical data of H—MRS and CTP of model,sham—operated and normal rats 3 DISCUSSION Cho/Cr ratio,there is no significant statistical difference among all of rats.NAA is recognized The 7.0 T small animaI MRI used in this pa— as a reflection of number and function of neu— per can clearly demonstrate the fine structure of rons[ .The NAA reduction reflects damage and the rat brain.MRT shows that there is no abnor— loss of neurons or axonal as well as dysfunction to mal change for the structure of striatum and other a certain extent .Although the loss of neurons tissues of the model and sham—operated rat is positively correlated with the age,rats in the brains.MRA shows that the structure of brain test are bred under the same condition in the same blood vessels is symmetrical and norma1.AIl of period,which can exclude the age factor that re— these mean that the PD rat brain has no signifi— suhs in the NAA/Cr ratio reduction.It indicates cant anatomy change compared with the normal that the injected side of striatum of the model rat rat,and lacks the characteristic performance in exists damage and loss of neurons and axonal, morphological imaging.MRI also clearly shows providing the diagnostic basis for the neuron dys— that the puncture needle road of the Success PD function of pDE10-12].The Cho/Cr ratio of the rat model is perpendicular to the rat brain in both striatum of the PD rat model does not change, sagittal and coronal planes.And the end point of which may be due to none or little proliferation of the puncture needle is exactly stopped at SNc, glial cells,or else,the proliferation cell having while the needle road of the failed rat model devi— tendency to balance for the long duration of rats. ates from SNc.The rat brain is relatively smal1. H—MRS directly reflects the metabolism changes Therefore,the slight offset can lead to an inaccu— of nerve ceils,and indirectly confirms the patho— rate puncture location and result in a failure logical changes of organizations,i.e.,the mold. changes of neurons,synapses and glial cells. The striatum is selected to carry out the Currently,the study of CBF of PD patients H—MRS examination.It is mainly because that is mainly carried out by positron emission tomog— the substantia nigra is narrow while the striatum raphy(PET)and single photon emission tomog— is relatively large.As a res ult,it is easy to posi— raphy(SPECT),but it is difficult to popularize tion and improve the test accuracy.Besides,SNc because of its expense,technical complexity and is selected as the injection location.It can avoid other reasons.CT brings unprecedented opportu— the damage of the striatum and insure the test ac.+ nities to study PD with the merits of convenience, curacy.Rasuhs show that the NAA/Cr ratio of economy,high time and space resolution,etc. the injected(right)side of the PD rat model is The 64一slice spiral CT used in this paper can scan significantly lower than the left side,bilateral all brain tissues of rat and its spatial and temporal sides of sham—operated and normal rats.As to the rcsolution are both meet the requirements of No.1 Hu Guangxia,et a1.Imaging Characteristics of Rat Models of Parkinson Disease 43 CTP.Res ults show that both regional CBF and yun.The rat brain in stereotaxic 153 Bao Xinmin,Shu Siregional CBV of the injected(right)side of the model rat are slightly lower than its left side,and its bilateral sides of sham—operated and normal rats.There is no significant statistical difference for the blood flow among the left side of the mod— el rat。and the bilateral sides of sham—operated and normal rats.The results agree well with the reported CBF changes of PD patients and animals coordinates[M].Beijing:People s Health Publishing House,1991.(in Chinese)  R,Sherer T B,Greenamyre J T.Animal [62 Betarbetmodels of Parkinson s disease[J].Bioessays,2002, 24(4):308—318. 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[15]Cilia R,Marotta G,Landi A,et a1.Cerebral aetivi— ty modulation by extradural motor cortex stimulation in Parkinson s disease:a perfusion SPECT study [J2.Eur J Neurol,2008,15(1):22—28. 44 Transactions of Nanjing University of Aeronautics&Astronautics Vol_27 帕金森大鼠模型的影像特性 胡光霞 钱志余 孙 涛 杨天明 王文宏 谢捷如 (1.南京航空航天大学自动化学院,南京,21001 6,中国;2.东南大学附属中大医院,南京,210009.中国) 摘要:利用影像技术对帕金森病(Parkinson disease,PD) 大鼠模型的脑形态与功能信息进行了系统研究。利用磁共 CTP)成像获取波谱及血流变化等功能影像学资料。研究结 果表明PD大鼠在形态上影像无特征性异常,在功能影像 振(Magnetic resonance imaging。MRI)及磁共振血管成像 (Magnetic resonance angiography,MRA)获取PD大鼠脑 部形态影像资料,利用质子磁共振波谱( H—magnetic reso— nance spectroscopy, H—MRS)及CT灌注(CT perfusion, 基金项目:国家自然科学基金(30671 997)资助项目。 学纹状体存在局部脑血流降低和波谱变化。 关键词:医学影像;脑形态;帕金森病;磁共振;CT灌注 中图分类号:R318;R445.2 

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