DWI与Gd-DTPA增强扫描诊断兔头颈转移淋巴结的比较研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:建立新西兰大白兔头颈部良恶性肿大淋巴结的动物模型,以病理学为金标准,比较相对表观弥散系数(rADC)和钆喷酸葡胺增强MR诊断兔头颈部转移淋巴结的准确性。
     材料和方法:20只新西兰大白兔雌雄不限,2-3个月龄,平均体重(2±0.5)kg。随机分成两组,每组10只。
     炎症组:用生鸡蛋黄与生理盐水按1:1体积比混合制成蛋黄乳胶,10只实验兔于右耳根部(外侧耳廓边缘和耳中央动脉之间,耳的下三分之一入颅处)每只注射3m1,3天后重复注射,每天观察兔子的日常情况,触摸头颈部淋巴结是否肿大,约1周建立炎性肿大淋巴结模型。
     荷瘤组:切取VX2荷瘤兔肿瘤边缘生长旺盛的鱼肉样组织,制成浓度为1×107个/ml的单细胞悬液;10只实验兔以3%戊巴比妥钠(30mg/kg)经耳缘静脉麻醉,于右耳根部(具体位置同上)注射瘤细胞悬液共0.5ml,接种后连续3天每天注射青霉素40万U,每天观察兔子的日常情况,触摸头颈部淋巴结是否肿大,约4周建立转移淋巴结模型。
     使用GE1.5T signal HDT MR扫描仪,膝关节线圈,实验兔采用3%戊巴比妥钠(30mg/kg)经耳缘静脉麻醉。兔颈部拉直、仰卧位、足先进。扫描范围从双耳根部连线至胸廓入口。扫描序列包括:横断面FSE T1W1.横断面FSE T2W1.横断面DWI序列,其中b值为1000s/mm2。注射钆喷酸葡胺(Gd-DTPA)80s后行T1WI序列扫描。测量淋巴结、同层肌肉的ADC值,计算淋巴结/肌肉的rADC值,测量增强前、后T1WI序列淋巴结/同层肌肉的信号强度值(SI),计算增强后/增强前信号强度比值(SIr),并进行统计学分析。最后取出淋巴结,测淋巴大小,进行组织病理学HE染色,确定淋巴结的性质。
     结果:经病理证实,炎症组取出淋巴结26枚,肿瘤组取出转移淋巴结14枚。转移淋巴结的长径为12.29±3.80mm,短径为7.95±2.10mm;炎性肿大淋巴结的长径为9.40±1.90mm,短径为5.60±2.10mm。转移淋巴结有9枚短径l0mm,有15枚长径/短径≤2,3枚发生中央坏死。
     炎症组反应增生淋巴结的rADC值为1.05±0.09,肿瘤转移组淋巴结的rADC值为0.78±0.10;反应增生淋巴结平均SIr值为1.34±0.25,肿瘤组转移淋巴结的SIr值为1.78±0.33。炎症组、肿瘤转移组淋巴结的rADC值、SIr值差异均具有统计学意义(t值分别为-8.30、4.76,p均<0.05)。利用rADC值鉴别良、恶性淋巴结ROC曲线下的面积(AUC)是0.93,阈值0.88,灵敏度92.3%,特异度92.9%;SIr值的AUC是0.81,阈值是1.66,灵敏度78.6%,特异度88.5%。
     结论:经兔右耳根部注射蛋黄乳胶、VX2肿瘤细胞可以建立头颈炎性、肿瘤转移性淋巴结模型;转移淋巴结与炎性淋巴结直径大小、长径/短径值重叠较大;炎症组肿大淋巴结、肿瘤转移组淋巴结的rADC值、SIr值具有差异性;rADC值比钆剂增强扫描SIr值鉴别转移性淋巴结具有较高的准确性。
[Objective]:
     To establish animal modes of benign and malignant lymph nodes with New Zealand white rabbits. To compare the diagnostic accuracy of the relative apparent diffusion coefficient(rADC) with gadolinium-enhanced MR in differentiating the metastatic lymph nodes in head and neck rabbit models,by using histologic analysis as the reference standard.
     [Materials and Methods]:
     20New Zealand white rabbits,male or female, age3to4months, body weight2.0-2.5kg, were randomly divided into two groups with10rabbits in each group.
     Established model of inflammation group:Making blend of egg yolk emulsion with raw egg yolk and saline1:1volume.The emulsion was inoculated concentrically between the lateral auricle edge and the central auricular artery into the cranial section of the lower third of right auricles by injecting3ml of blend of egg yolk emulsion.The same procedure was repeated after three days.From the first day after inoculation,growth and the head and neck lymph node enlargement were observed every day.
     Established model of VX2carcinoma malignant group:Cut the Vigorous growth strong fish-like organization of tumor edge in VX2tumor-bearing rabbit, made into tumor cell suspension of1×10ml;10rabbits Were anesthetized with3%sodium pentobarbital (30mg/kg) via marginal ear vein,VX2carcinoma was inoculated concentrically between the lateral auricle edge and the central auricular artery into the cranial section of the lower third of right auricles by injecting tumor cell suspension0.5ml.Intramuscular injection (4×105U/day) of penicilin was administered for the three consecutive days to prevent infection. From the first day after inoculation,growth and the head and neck lymph node enlargement were observed every day.
     All subjects were examined with GE1.5T signal HDT MR scanner using knee coil. Rabbits were anesthetized with3%sodium pentobarbital (30mg/kg) via the marginal ear vein Straighten rabbits neck, Supine position, feet first. Scan range was from the ears roots connect to the thoracic inlet.Scanning sequences included cross sectional FSE T1-weighted image(TlWI), cross sectional FSE T2-weighted image(T2WI),and cross sectional diffusion weighted imaging (DWI) sequence scan were performed on each model, After80seconds administration of Gd-DTPA FSE T1WI were acquired. lymph nodes, the same level of muscle's ADC values were measured and lymph node/muscle rADC value were calculated.lymph nodes/the same level of muscle's standardized signal intensities (SI) values were measured before and after Gd-DTPA enhanced T1WI sequences, the SIpost/SIpre value (SIr)were calculate and analyzed statistically. Finally get the lymph nodes, measuring the size of lymph nodes, and diagnose the nature of lymph node by histopathology HE staining.
     [Results]:
     Confirmed by pathology, the number of lymph nodes from inflammation group were26, the number of lymph nodes from tumor group were14. The long diameter of metastasis lymph node is12.29±3.80mm, short diameter is7.95±2.10mm;the long diameter of inflammatory lymph nodes is9.40±1.90mm, short diameter is5.60±2.10mm. The number of the metastasis lymph nodes short diameter<10mm is9, the number of long diameter/short diameter≥2is3; inflammatory lymph nodes2short diameter>10mm, the number of long diameter/short diameter≤2is15,3lymph nodes has central necrosis.
     The rADC value of inflammation group lymph nods is1.05±0.09, the rADC value of malignant group lymph nods is0.78±0.10;the SIr value of inflammation group lymph nods is1.34±0.25, the SIr value of malignant group lymph nods is1.78±0.33.Independent-Samples T Test were conducted to compare the differences of benign and malignant lymph nodes.rADC value, Sir value,both were statistically significant (t value were-8.30、4.76respectively,all P <0.05).
     A receiver operating characteristic analysis was conducted to compare the diagnostic value of rADC value and SIr value,when using rADC value area under the ROC curve (AUC) was0.93, and the threshold value of rADC was0.88, while the sensitivity, specificity was92.3%,92.9%respectively; when using SIr value the AUC area was0.81, the threshold was1.66, the sensitivity, specificity was78.6%,88.5%respectively.
     [Conclusion]:
     The diameter of malignant lymph node and inflammatory lymph node, long diameter/short diameter values overlap larger. There is a difference of rADC value and SIr value of lymph nodes between Inflammation and neoplasms metastasis groups. rADC value can be more accurate than SIr value in differentiating benign and malignant lymph nodes in rabbit models.
引文
[1]Curtin HD, Ishwararn H,Mancuso AA, et al. Comparison of CT and MRI imaging in staging of neck metastases[J]. Radiology,1998,207(1):123-130.[2]Vanden Brekel MW, Stel HV, Castelijns JA, et al. Cervical lymph nodes metastasis: assessment of radiologic criteria [J]. Radiology,1990,177(2):379-384.[3]Steinkamp HJ, Hosten N, Richter C, et al. Enlarged cervical lymph nodes at helical CT [J].Radiology,1994,191(3):795-798.[4]苏勇,赵充,谢传淼,等.鼻咽癌咽后淋巴结转移的CT、MRI和PET-CT诊断的对比研究[J].癌症,2006,25(5):521-525.[5]Bammer R.Basic principles of diffusion weighted imaging[J].Eur Radiol,2003,45(3):169-184.[6]Stadnik TW, Demaerel P, Luypaert RR, et al.Imaging tutorial:differential diagnosis of bright lesions on diffusion-weighted MR images [J].Radiographics,2003,23(1):3-7.[7]King AD, Ahuja AT, Yeung DK, et al. Malignant cervical lymphadenopathy diagnostic accuracy of diffusion-weighted MR imaging[J]. Radiology,2007,245(3):806—813.[8]De Bondt RBJ, Hoeberigs MC, Nelemans PJ.Diagnostic accuracy and additional value of diffusion-weighted imaging for discrimination of malignant cervical lymph nodes in head and neck squamous cell carcinoma [J].Neuroradiology,2009,51:183-192.[9]Yanagisawa O, Shimao D, Maruyama K, et al. Diffusion-weighted magnetic resonance imaging of human skeletal muscles:gender-, age-and Muscle-related differences in apparent diffusion coefficient. Magn Reson Imaging,2009,27(1):69-78.[10]Xie CM, Yin SH,Li H.Diagnostic value of ADC and rADC of diffusion weighted imaging in malignant breast lisions.[J]zhonghua zhongliu zazhi.2010,32(3):17-20.[11]Park SO,Kim JK,Kim KA, et al. Relative apparent diffusion coefficient:determination of reference site and validation of benefit for detecting metastatic lymph nodes in uterine cervical cancer[J].J Magn Reson Imaging.2009,29(2):383—390.[12]Steinkamp HJ,Mueffelmann M,Bock JC, et al. Differential dignosis of lymph node lesion:a semiquantitative approach with colour Dopple ultrasound[J]. Br J Radiol,1998,71(848):828-833.[13]Wagner S.Benign lymph node hyperplasia and lymph node metastases in rabbits:Animal models for magnetic resonance lymphography[J].Invest Radiol,1994,29:364-371.[14]Choi SH, Han MH, Moon WK, et al. Cervical Lymph Node Metastases:MR Imaging of Gadofluorine M and Monocrystalline Iron Oxide Nanoparticle-47in a Rabbit Model of Head and Neck Cancer [J].Radiology2006,241(3):753-762.[15]杨炼,柳熙,徐海波等.经组织间隙注射Dextran Gd—DTPA兔胭窝淋巴结MRI一种新型MR对比剂的初步应用[J].放射学实践,2009,24(9):971-975.[16]Dunne AA,Plehn S,Schulz S,et al.Lymph node topography of the head and neck in New Zealand White rabbits [J]. Lab Anim,2003,37(1):37-43.[17]黄江琼、王安宇、朱小东等.兔鼻咽VX2移植癌模型的建立及其生长转移特性[J]。中国肿瘤临床.2009,36(4):222-226.[18]Jefferis AF,Berenbaum MC.The rabbit VX2tumor as a model for carcinomas of the tongue and larynx[J].Acta Otolaryngol,1989,108(1-2):152-160.[19]沈毅,孙坚,周晓健,等.兔舌不同部位VX-2鳞癌与颈淋巴结转移模型的生物学特性[J].上海口腔医学,2007,16(5):497-501.[20]Dunne AA,Mandic R,Ramaswamy A,et al.Lymphogenic metastatic spread of auricular VX2carcinoma in New Zealand white rabbits[J].Anticancer Res,2002,22(6A):3273-3279.[21]Lee KC,Moon Wk,Chung JW,et al. Assessment of lymph node metastases by contrast-enhanced MR imaging in a head and neck cancer model[J].Korean J Radiol,2007,2(1):9-14.[22]Vanden Brekel MW, Castelijns JA, Snow GB.The size of lymph nodes in the neck on sonograms as a radiologic criterion for metastasis:how reliable is it?[J]. AJNR,1998,19(4):695-700.[23]欧阳涛,唐石初.颈部淋巴结肿大的超声影像参数分析医学临床研究,2009,26:593-596.[24]Na DG, Lim HK, Byun HS, et al. Different Diagnosis of Cervical Lymphadenopathy: Usefulness of Color Doppler Sonography[J]. AJR,1997,168(5):1311—1316.[25]Shin LK, Fischbein NJ, Kaplan MJ,et al. Metastatic squamous cell carcinoma presenting as diffuse and punctate cervical lymph node calcifications:sonographic features and utility of sonographically guided fine-needle aspiration biopsy. Journal of Ultrasound in Medicine,2009,28:1703-1707.[26]Dangore-Khasbage S, DegwekarSS, BhowateRR, et al."Utility of color Doppler ultrasound in evaluating the status of cervical lymph nodes in oral cancer," Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology,2009,108(2):255-263.[27]Lyshchik A, Higashi T, Asato R, et al. Cervical lymph node metastases:diagnosis at sonoelastography-initial experience [J].Radiology,2007,243(1):258-267[28]罗德红石木兰.颈部转移淋巴结的CT、B超扫描与病理对照研究.中华放射学杂志,1997-09-010.[29]Yang WT, Lam WW, Yu MY, et al.Comparison of dynamic helical CT and dynamic MR imaging in the evaluation of pelvic lymph nodes in cervical carcinoma. Am J Roentgenoi,2000,175:759-766.[30]叶兆祥、肖建宇.CT灌注成像对颈部淋巴结病变的诊断价值.中国肿瘤影像学,2009,2(3):38-41.[31]梁颖,罗德红,吴宇等.颈部恶性淋巴结的多层螺旋CT灌注研究.中华放射学杂??志,2004,38(11):1193-1197.[32]Vail den Brekel MW. Lymph node metastases:CT and MRI. Eur J Radiol.2000,33(3):230-238.[33]Steinkamp HJ, Cornehl M, Hosten N et al:Cervical lymphadenopathy:ratio of long-to short-axis diameter as a predictor of malignancy. Br J Radiol1995,68:266-270.[34]Steinkamp HJ,Mueffelmann M,Bock JC, et al. Differential dignosis of lymph node lesion:a semiquantitative approach with colour Dopple ultrasound[J]. Br J Radiol,1998,71(848):828-833.[35]Adams S,Banm RP, Stuckensen T, et al. Prospective comparison of18F-FDG PET with conventional imaging modalities (CT, MRI,US) in lymph node stuging of head and neck cancer[J]. Eur J NuclMed,1998,25(9):1255-1260.[36]Abdel Razek AA, Soliman NY, Elkhamary S, et al. Role of diffusion-weighted MR imaging in cervical lymphadenopathy [J]. Eur Radiol,2006,16(7):1468-1477.[37]陈杰、邢伟、生晶等.相对表观弥散系数鉴别兔良、恶性淋巴结[J].中国医学影像技术,2010,26(10):1819-1822.[38]Vincent V, Frederik DK,Vincent VP. Head and Neck Squamous Cell Carcino-ma:Value of Diffusion weighted MR Imaging for Nodal Staging[J]. Radiology,2009,251(1):134-146.[39]Akduman EL. Momtahen A.J, Balci NC, et al. Compmson between malignant and benign abdominal lymph nodes on diffusion—weighted imaging [J]. Acid Radiol,2008,15:641-646.[40]Thoeny HC, De Keyzer F, Chen F, et al. Diffusion-weighted MR imaging in monitoring the effect of a vascular targeting agent on rhabdomyosarcoma in rats [J].Radiology2005,234:756-764.[41]Herneth AM, Guccione S, Bednarski M. Apparent diffusion coefficient:a quantitative parameter for in vivo tumor characterization[J]. Eur J Radiol2003,45:208-213.[1]Vanden Brekel MW, Castelijns JA, Snow GB.The size of lymph nodes in the neck on sonograms as a radiologic criterion for metastasis:how reliable is it?[J]. AJNR,1998,19(4):695-700.[2]欧阳涛,唐石初.颈部淋巴结肿大的超声影像参数分析医学临床研究,2009,26:593-596.[3]Moritz JD, Ludwig A, Oestmann JW. Contrast-enhenced colour Dopple Sonography for evaluation of enlarged cervical lymph nodes in head and neck tumors [J]. A JR,2000,174(5):1279-1284.[4]Na DG, Lim HK, Byun HS, et al. Different Diagnosis of Cervical Lymphadenopathy: Usefulness of Color Doppler Sonography [J]. AJR,1997,168(5):1311—1316.[5]Shin LK, Fischbein NJ, Kaplan MJ,et al. Metastatic squamous cell carcinoma presenting as diffuse and punctate cervical lymph node calcifications:sonographic features and utility of sonographically guided fine-needle aspiration biopsy. Journal of Ultrasound in Medicine,2009,28:1703-1707.[6]Dangore-Khasbage S,.DegwekarSS, BhowateRR, et al."Utility of color Doppler ultrasound in evaluating the status of cervical lymph nodes in oral cancer," Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology,2009,108(2):255-263.[7]李霞,李静.头颈部恶性肿瘤患者颈部肿大淋巴结的超声诊断,临床超声医学杂志,2010,2,12(2):127-128.[8]洪玉蓉,刘学明.超声造影定量分析在浅表淋巴结疾病鉴别诊断中的应用.中国超声医学杂志,2007,3:212-214.[9]Lyshchik A, Higashi T, Asato R, et al. Cervical lymph node metastases:diagnosis at sonoelastography-initial experience [J].Radiology,2007,243(1):258-267[10]罗德红石木兰.颈部转移淋巴结的CT、B超扫描与病理对照研究.中华放射学杂志,1997-09-010.[11]叶兆祥、肖建宇.CT灌注成像对颈部淋巴结病变的诊断价值.中国肿瘤影像学,2009,2(3):38-41.[12]于海容王振常.颈部淋巴结病变的CT灌注成像研究.医学临床研究,2009,26(3):46-49.[13]梁颖,罗德红,吴宇等.颈部恶性淋巴结的多层螺旋CT灌注研究.中华放射学杂志,2004,38(11):1193-1197.[14]Steinkamp HJ, Cornehl M, Hosten N et al:Cervical lymphadenopathy:ratio of long-to short-axis diameter as a predictor of malignancy. Br J Radiol1995,68:266-270.[15]Steinkamp HJ,Mueffelmann M,Bock JC, et al. Differential dignosis of lymph node lesion:a semiquantitative approach with colour Dopple ultrasound[J]. Br J Radiol,1998,71(848):??828-833.[16]Sugahara T, Korogi Y, Kochi M, et al. Usefulness of diffusion weighted MRI with echo-p lanner technique in the evalution of celluarity in gliomas[J]. J Magn Reson Imaging,1999,9(1):53-60.[17]Gray L, Macfall J. Overview of diffusion imaging [J]. MRI Clin NAm,1998,6(1):125-138.[18]Stadnik TW, Demaerel P, Luypaert RR, et al.Imaging tutorial:differential diagnosis of bright lesions on diffusion-weighted MR images [J]. Radiographics,2003,23(1):3-7.[19]Abdel Razek AA, Soliman NY, Elkhamary S, et al. Role of diffusion-weighted MR imaging in cervical lymphadenopathy[J]. Eur Radiol,2006,16(7):1468-1477.[20]King AD, Ahuja AT, Yeung DK, et al. Malignant cervical lymphadenopathy:diagnostic accuracy of diffusion-weighted MRimaging[J].Radiology,2007,245(3):806—813.[21]De Bondt RBJ, Hoeberigs MC, Nelemans PJ.Diagnostic accuracy and additional value of diffusion-weighted imaging for discrimination of malignant cervical lymph nodes in head and neck squamous cell carcinoma [J].Neuroradiology,2009,51:183-192.[22]Yanagisawa O, Shimao D, Maruyama K, et al. Diffusion-weighted magnetic resonance imaging of human skeletal muscles:gender-, age-and muscle-related differences in apparent diffusion coefficient. Magn Reson Imaging,2009,27(1):69-78.[23]Park SO,Kim JK,Kim KA, et al. Relative apparent diffusion co-efficient:determination of reference site and validation of benefit for detecting metastatic lymph nodes in uterine cervical cancer[J].J Magn Reson Imaging.2009,29(2):383—390.[24]Choi SH, Han MH, MoonWK, et al. Cervical lymph node metastases:MR Imaging of Gadofluorine M and Monocrystalline Iron OxideNanoparticle-47in a rabbit model of head and neck cancer[J]. Radiology,2006,24(3):753-762.[25]SumiM, Sakihama N, Sumi T, et al. Discrimination of metastatic cervical lymph nodes with diffusion-weighted MR imaging in patient with head and neck cancer[J]. AJNR,2003,24(8):1672-1634.[26]vandeeaveye V, De Keyzer F,Nuyts S,et al.Deteetion of head and neck Squamous cell carcinoma with diffusion weighted MRI after(chemo)radiotherapy:correlation between radiologic and histopathlogic findings[J].Int J Radiat Oncol Biol Phys,2007,67(4):960-971.[27]Saokar A,Braschi M,Harisinghani M.Lymphotrophic nanoparticle enhanced MR imaging(LNMRI) for lymph node imaging[J].Abdom Imaging,2006,31(6):660-667.[28]薛华丹,雷晶.超顺磁性纳米氧化铁颗粒淋巴结成像及其与病理超微结构的比较.中国医学科学院学报,2009,02:139-145.[29Baghi M, Mack MG, Wagenblast J,et al.Iron Oxide Particle-enhanced Magnetic Resonance Imaging for Detection of Benign Lymph Nodes in the Head and Neck:How Reliable are the Results?[J]ANTICANCER RESEARCH (2007)27:3571-3575.[30]Sigal R,Vogl T,Casselman J,et al. Lymph node metastases from head and neck squamous cell carcinoma:MR imaging with ultrasmall superparamagnetic iron oxide particles (Sinerem MR)-result s of a Phase-Ⅲ Multicenter clinical trial [J]. Eur Radiol,2002,12(5):1104-1113.[31]Anzai Y,Brunberg JA,Luf kin RB. Imaging of Nodal Metastases in the Head and Neck[J]. J Magn Reson Imaging,1997,7(5):774-783.[32]Jeong HS,Baek CH,Son YI,et al. Use of Integrated (18) F-FDG PET/CT to Improve t he Accuracy of Initial Cervical Nodal Evaluation in Patients with Head and Neck Squamous Cell Carcinoma [J]. Head Neck,2007,29(3):203-210.[33]Ke Z,Liu M,Liu Y,et al. Diagnostic Value of18F-FDG PET/CT in the Detection of the Cervical Lymph Nodes Metastasis[J]. Lin Chuang Er Bi Yan Hou Ke Za Zhi,2006,20(6):243-245.[34]Mehran Baghi, Marting Mack.The Efficacy of MRI with Ultrasmall Superparamagnetic Iron Oxide Particles (USPIO) in Head and Neck Cancers [J]. ANTIC ANCER RESEARCH2005,25:3665-3670.[35]Bendszus M,Warmuth M, Klein R, et al. MR spectroscopy in gliomatosis cerebri[J]. AJNR,2000,21(2):375-380.[36]King AD, Yeung DK,Ahuja AT, et al. In vivo p rotonMR spectroscopy of primary and nodal nasopharyngeal carcinoma [J]. AJNR,2004,25(3):484-490.[37]Bisdas S, Baghi M, Huebner F, et al. In vivo proton MR spectroscopy of primary tumours, nodal and recurrent disease of the extracranial head and neck [J]. Eur Radiol,2007,17(1):251-257.[38]Sumi M, Van Cauteren M, Nakamura T. MR microimaging of benign and malignant nodes in the neck [J]. AJR,2006,186(3):749-757.[39]Yen TC,Chang JT,Ng SH,et al.The value of18F-FDGPET in the detection of stage MO carcinoma of the nasopharynx [J].J Nucl Med,2005,46(3):405-410.[40]Kosky M,Paulino AC,Howell R,et al.18F-FDG PET/CT fusion in radiotherapy treatment planning for head and neck cacer.Head Neck,2005,27(6):494-499.[41]张云,杨小丰.PET/CT在头颈部肿大淋巴结定性中的临床价值.中华医学影像杂志,2010,18(1):83-85.[42]Adams S,Banm RP, Stuckensen T, et al. Prospective comparison of18F-FDG PET with conventional imaging modalities (CT, MRI,US) in lymph node stuging of head and neck cancer[J]. Eur J NuclMed,1998,25(9):1255-1260.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700