Evaluation of a rabbit rectal VX2 carcinoma model using computed tomography and magnetic resonance imaging

AIM: To establish a rabbit rectal VX2 carcinoma model for the study of rectal carcinoma. METHODS: A suspension of VX2 cells was injected into the rectum wall under the guidance of X-ray fluoroscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to observe tumor growth and metastasis at different phases. Pathological changes and spontaneous survival time of the rabbits were recorded. RESULTS: Two weeks after VX2 cell implantation, the tumor diameter ranged 4.1-5.8 mm and the success implantation rate was 81.8%. CT scanning showed low-density foci of the tumor in the rectum wall, while enhanced CT scanning demonstrated asymmetrical intensification in tumor foci. MRI scanning showed a low signal of the tumor on T1-weighted imaging and a high signal of the tumor on T2-weighted imaging. Both types of signals were intensified with enhanced MRI. Metastases to the liver and lung could be observed 6 wk after VX2 cell implantation, and a large area of necrosis appeared in the primary tumor. The spontaneous survival time of rabbits with cachexia and multiple organ failure was about 7 wk after VX2 cell implantation. CONCLUSION: The rabbit rectal VX2 carcinoma model we established has a high stability, and can be used in the study of rectal carcinoma.

MR diffusion-weighed imaging of rabbit liver

AIM: To study the techniques of MR diffusion-weighed imaging (DWI) for normal rabbit liver.METHODS: After 15 normal New Zealand white rabbits and one New Zealand white rabbit implanted with VX-2 tumor were anesthetized with 3% soluble pentobarbitone,DWI was performed respectively for different b values,repetition times (TR) or thicknesses, when other parameters were the same and magnetic resonance imaging (MRI)was performed respectively, or with different field of views (FOV) or coil when other parameters were the same. The distinction between groups was analyzed by SPSS10.0 with apparent diffusion coefficient (ADC), quality index (QI) or signal-noise ratio (SNR).RESULTS: As b value increased, liver ADC, QI and SNR of DWI became smaller and simultaneously (F= 292.87,156.1, 88.23, P＜0.01). QI of DWI was high, when bvalue was 10, 50 or 100 respectively, but the distinction between them was insignificant; when b value was 800, QI and SNR of DWI were low. QI and SNR of DWI had no significant difference between TR = 4 000, 6 000 and 8 000. QI of DWI with 2 mm thickness was bigger than that with 5 mm thickness (t = 3.04, P＜0.01), but SNR of DWI with 2 mm thickness was significantly smaller (t = -17.86, P＜0.01).SNR of MRI with knee joint coil was obviously bigger than that with cranium coil [t = -5.77 (T1WI) or -4.02 (T2WI),P＜0.01], but QI of MRI was smaller on the contrary [t = 7.10 (T1WI) or 3.97 (T2WI), P＜0.01]. When FOV was enlarged gradually, SNR of MRI increased [F= 85.81 (T1WI) or 221.96 (T2WI), P＜0.01], but QI firstly increased, then decreased [F= 68.67 (T1WI) or 69.46 (T2WI), P＜0.01] and QI of MRI was the biggest when FOV was 20 cm×15 cm.CONCLUSION: The scanning technique is very important in DWI of rabbit liver and the overall quality of DWI with b (100 s/mm2), thickness (2 mm), cranium coils and FOV (20 cm× 15 cm) was best in our study, when other parameters were the same.

MR diffusion-weighted imaging of rabbit liver VX-2 tumor

AIM: To investigate the implanting method of rabbit liver VX-2 tumor and its MR diffusion-weighted imaging (DWI) characteristics.METHODS: Thirty-five New Zealand rabbits were included in the study. VX-2 tumor was implanted subcutaneously in 14 rabbits and intrahepatically in 6 for pre-experiments. VX-2 tumor was implanted intrahepatically in 12 rabbits for experiment and three were used as the control group. DWI, T1- and T2-weighted of MR1 were performed periodically in 15 rabbits for experiment before and after implantation. The distinction of VX-2 tumors on DWI was assessed by their apparent diffusion coefficient (ADC) values. The statistical significance was calculated byanalysis of variance (ANOVA) of the randomized block design using SPSS10.0 software. RESULTS: The successful rate of subcutaneous implantation of VX-2 tumor was 29% (4/14) while that of intrahepatic implantation of it was 33% (2/6) in the preexperiment. The successful rate of intrahepatic implantation of VX-2 tumor in the experiment was 83% (10/12) and 15 tumors grew in 10 successfully implanted rabbits. The DWT signal of VX-2 tumor was high and became lower when the b value increased step by step. The signal of VX-2 tumor on the map of ADC was low. When the b value was 100 or 300 s/mm2, the ADC value of normal group and VX-2 tumor group was respectively 2.57±0.26, 1.73±0.31, 1.87±0.25 and 1.57±0.23 mm2/s. Their distinction was significant (F= 43.26, P＜0.01), the tumor ADC value between b values 100 and 300 s/mm2 wassignificant (Tukey HSP, P＜0.05) and the ADC value between VX-2 tumor and normal liver was also significant (Tukey HSP, P＜0.01). VX-2 tumor developed quickly and metastasized early to all body, especially to the lung, liver, lymph nodes of mediastinum, etc.CONCLUSION: The DWI signal of rabbit VX-2 tumor has its characteristics on MR DWI and DWI plays an important role in diagnosing and discovering VX-2 tumor.

铁沉积对非酒精性脂肪性肝炎兔模型肝脏质子密度脂肪分数的影响

目的建立兔非酒精性脂肪性肝炎(NASH)模型,观察铁沉积对肝脏质子密度脂肪分数(PDFF)的影响。方法将70只新西兰大白兔随机分为单纯高脂组(A组,n=35)及高脂联合铁剂组(B组,n=35);再将B组分为1、2、3、4、8、12及16 ml共7个亚组,每组5只。对A组以高脂饲料饲养,对B组以高脂饲料饲养并经耳缘静脉注射右旋糖酐铁溶液(含铁100 mg/ml),建立NASH模型;行MRI及病理学检查,观察基于MRI所测PDFF与基于病理所测脂肪分数(FF)的相关性。结果建模结束时A、B组兔存活率分别为91.43%和74.29%,建模用时分别为(7.27±1.01)周和(5.07±1.27)周。B组各亚组中,随注射铁含量增加,MRI显示肝脏信号逐渐减低、胆囊及大血管显示欠清,其中1及2 ml亚组拟合优度分数均<5%、其余各亚组均≥5%,且仅1及2 ml亚组PDFF与FF相关(r=0.961、0.893,P=0.039、0.041)。结论NASH模型兔肝脏铁沉积增加将影响MRI测量肝脏PDFF的准确性。

Role of MR-DWI and MR-PWI in the radiotherapy of implanted pulmonary VX-2 carcinoma in rabbits

Objective： To detect the activity of tumor cells and tumor blood flow before and after the radiotherapy of implanted pulmonary VX-2 carcinoma in rabbit models by using magnetic resonance diffusion-weighted imaging（MR-DWI） and magnetic resonance perfusion weighted imaging（MR-PWI）, and to evaluate the effectiveness and safety of the radiotherapy based on the changes in the MR-DWI and MR-PWI parameters at different treatment stages.Methods： A total of 56 rabbit models with implanted pulmonary VX-2 carcinoma were established, and then equally divided into treatment group and control group. MR-DWI and MR-PWI were separately performed using a Philips Acheiva 1.5T MRI machine（Philips, Netherland）. MRI image processing was performed using special perfusion software and the WORKSPACE advanced workstation for MRI. MRDWI was applied for the observation of tumor signals and the measurement of apparent diffusion coefficient（ADC） values; whereas MR-PWI was used for the measurement of wash in rate（WIR）, wash out rate（WOR）, and maximum enhancement rate（MER）. The radiation treatment was performed using Siemens PRIMUS linear accelerator. In the treatment group, the radiotherapy was performed 21 days later on a once weekly dosage of 1,000 c Gy to yield a total dosage of 5,000 c Gy.Results： The ADC parameters in the region of interest on DWI were as follows： on the treatment day for the implanted pulmonary VX-2 carcinoma, the t values at the center and the edge of the lesions were 1.352 and 1.461 in the treatment group and control group（P〉0.05）. During weeks 0-1 after treatment, the t values at the center and the edge of the lesions were 1.336 and 1.137（P〉0.05）. During weeks 1-2, the t values were 1.731 and 1.736（P〈0.05）. During weeks 2-3, the t values were 1.742 and 1.749（P〈0.05）. During weeks 3-4, the t values were 2.050 and 2.127（P〈0.05）. During weeks 4-5, the t values were 2.764 and 2.985（P〈0.05）. The ADC values in the treatment group were significantly higher than in the control group. After the radiotherapy（5,000 c Gy）, the tumors remarkably shrank, along with low signal on DWI, decreased signal on ADC map, and remarkably increased ADC values. As shown on PWI, on the treatment day for the implanted pulmonary VX-2 carcinoma, the t values of the WIR, WOR, and MER at the center of the lesions were 1.05, 1.31, and 1.33 in the treatment group and control group（P〉0.05）; in addition, the t values of the WIR, WOR, and MER at the edge of the lesions were 1.35, 1.07, and 1.51（P〉0.05）. During weeks 0-1 after treatment, the t values of the WIR, WOR, and MER at the center of the lesions were 1.821, 1.856, and 1.931（P〈0.05）; in addition, the t values of the WIR, WOR, and MER at the edge of the lesions were 1.799, 2.016, and 2.137（P〈0.05）. During weeks 1-1 after treatment, the t values of the WIR, WOR, and MER at the center of the lesions were 2.574, 2.156, and 2.059（P〈0.05） and the t values of the WIR, WOR, and MER at the edge of the lesions were 1.869, 2.058, and 2.057（P〈0.05）. During weeks 2-3 after treatment, the t values of the WIR, WOR, and MER at the center of the lesions were 2.461, 2.098, and 2.739（P〈0.05） and the t values of the WIR, WOR, and MER at the edge of the lesions were 2.951, 2.625, and 2.154（P〈0.05）. During weeks 3-4 after treatment, the t values of the WIR, WOR, and MER at the center of the lesions were 2.584, 2.107, and 2.869（P〈0.05） and the t values of the WIR, WOR, and MER at the edge of the lesions were 2.057, 2.637, and 2.951（P〈0.05）. During weeks 4-5 after treatment, the t values of the WIR, WOR, and MER at the center of the lesions were 2.894, 2.827, and 3.285（P〈0.05） and the t values of the WIR, WOR, andMER at the edge of the lesions were 3.45, 3.246, and 3.614（P〈0.05）. After the radiotherapy（500 c Gy）, the tumors shrank on the T1 WI, WIR, WOR, and MER; meanwhile, the PWI parameter gradually decreased and reached its minimum value.Conclusions： MR-DWI and MR-PWI can accurately and directly reflect the inactivation of tumor cells and the tumor hemodynamics in rabbit models with implanted pulmonary VX-2 carcinoma, and thus provide theoretical evidences for judging the clinical effectiveness of radiotherapy for the squamous cell carcinoma of the lung.

Comparison of two different laparotomy methods for modeling rabbit VX2 hepatocarcinoma

AIM:To compare two different laparotomy methods for modeling rabbit VX2 hepatocarcinoma.METHODS:Thirty New Zealand rabbits were randomly divided into two groups:A and B.Group A was assigned a traditional laparotomy method(embedding tumor fragments directly into the liver with tweezers).Group B was subjected to an improved laparotomy method(injection of tumor fragments into the liver through a 15 G syringe needle).The operation time, incision length, incision infection rate, and mortality rate were compared between the two groups after laparotomy.Magnetic resonance imaging(MRI) was performed to evaluate tumor formation rates and the characteristics of the tumors 2 wk after laparotomy.RESULTS:The mean operation times for the two groups(Group A vs Group B) were 23.2 ± 3.4 min vs 17.5 ± 2.9 min(P < 0.05); the incision length was 3.3 ± 0.5 cm vs 2.4 ± 0.6 cm(P < 0.05); and the mortality rate after 2 wk was 26.7% vs 0%(P < 0.05); all of these outcomes were significantly different between the two groups.The incision infection rates in the two groups were 6.7% vs 0%(P > 0.05), whichwere not significantly different.MRI performed after 2weeks showed that the tumor formation rates in the two groups were 90.9%vs 93.3%(P>0.05).These rates were not significantly different between the two groups.The celiac implantation rate and abdominal wall metastasis rate in the two groups were 36.4%vs 13.3%(P<0.05)and 27.2%vs 6.7%(P<0.05),respectively,which were significantly different between the two groups.CONCLUSION:The tumor formation rates were not significantly different between the two methods for modeling rabbit VX2 hepatocarcinoma.However,the improved method is recommended because it has certain advantages.

Magnetic resonance imaging features of vulnerable plaques in an atherosclerotic rabbit model

Background Noninvasive detection of vulnerable plaque has a significant implication for prevention and treatment of atherosclerotic disea±ses. The aim of this study is to investigate the difference between vulnerable plaques and stable plaques in magnetic resonance （MR） images. Methods Atherosclerosis was induced in twenty male New Zealand white rabbits by high cholesterol diet and balloon injury of the abdominal aorta. After baseline （pre-triggering） MR imaging （MRI） scan, the rabbits underwent pharmaceutical triggering with Russell＇s viper venom and histamine to induce atherothrombosis, followed by another MRI scan 48 hours later （post-triggering）. Rabbits were euthanized to obtain pathological and histological data. The results of MRI were compared with those of pathology and histology. Results MRI showed that abdominal aorta of the rabbits had pathological change of atherosclerosis in different degrees. Seventy-five plaques were analysed, among which 14 had vulnerable thrombi and 61 stable. Thrombosis was identified in 7 of 11 rabbits by post-triggering MRI, the sensitivity and K value of MR in detection of vulnerable plaque was 71% and 0.803 （P 〈0.05）. MRI data significantly correlated with the histopathological data in fibrous cap thickness （t=0.749） plaque area （t=0.853）, lipid core area （r=0.900）. Compared with stable plaques, vulnerable plaques had a significantly thinner fibrous cap （（0.58±0.27） mm vs. （0.95±0.22） mm）, larger lipid core area （（7.56±2.78） mm2 vs. （3.29±1.75） mm2）, and a higher ratio of lipid core area/plaque area （（55±16）% vs. （27±17）%）, but plaque area was comparable in two groups on MRI. The ratio of lipid core area/plaque area was a strong predictor of vulnerable plaques. Conclusion MRI could distinguish vulnerable plaques from stable plaques in a rabbit model of atherothrombosis and may thus be useful as a noninvasive modality for detection of vulnerable plaques in humans.

Feridex-labeled bone marrow stromal cells for analysis of sciatic nerve defects in rabbits

BACKGROUND： Traumatic approaches, such as sacrifice and perfusion sampling, have been used to evaluate efficiency of stem cell transplantation. However, these methods are not applicable to human studies. Cell tracing, in combination with non-invasive imaging technology, can be utilized to trace cell survival following transplantation to evaluate the efficacy of cell transplantation therapy. OBJECTIVE： To explore feasibility of magnetic resonance imaging （MRI） to observe in vivo repair of injured sciatic nerves following feridex and polylysine （FE-PLL） complex-labeled bone marrow stromal cell （BMSC） transplantation. DESIGN, TIME AND SE＇I-rlNG： A randomized, controlled, animal experiment was performed at the Laboratory of the Department of Neurosurgery, Zhujiang Hospital from March to December 2008. MATERIALS： Feridex was purchased from Advanced Magnetic, USA, and polylysine was purchased from Sigma, USA. METHODS： BMSCs were harvested from adult rabbit femurs and were cultured in vitro with neural stem cell culture medium, leukemia inhibitory factor, and basic fibroblast growth factor. Bone marrow stromal cell-derived neural stem cells （BMSC-D-NSCs） were obtained and labeled with FE-PLL complex. The right sciatic nerve （0.8 mm） was excised from healthy, New Zealand rabbits, aged 1.5 months, and the epineuria of distal stumps underwent turnover and were anastomosed at the proximal ends. FE-PLL labeled BMSC-D-NSC suspension or culture medium was transplanted into the epineunal lumen using a microsyringe. The left sciatic nerve was left intact and sewed as the normal control. MAIN OUTCOME MEASURES： Cellular morphology, proliferation, and differentiation, as well as expression of nestin and neuron-specific enolase （NSE）, of BMSCs-D-NSCs were observed. Efficacy of FE-PLL labeling and effects on cells were measured. In addition, neural regeneration at 2, 8, and 16 weeks following transplantation was observed by MRI. Histopathology and mean number of regenerated nerve fibers in the proximodistal-injured sciatic nerve were evaluated by hematoxylin and eosin and Bielschowsky staining. RESULTS： Results demonstrated that BMSCs expanded, proliferated, and differentiated into neural-like cells with slim, long processes. The cells expressed nestin and NSE, as detected by immunocytochemistry. BMSC-D-NSCs were effectively labeled by FE-PLL, with a labeling efficiency of 98%. In addition, cell viability was not influenced by the FE-PLL complex. MRI results revealed low signals in the FE-labeled BMSC-D-NSC-implanted region of the sciatic nerve. A low-signal region was observed at 2 weeks, which was widely spread at 8-16 weeks after cell transplantation. The regenerated nerve fibers were orderly arranged in the cell transplantation group and exhibited no significant differences compared with the normal control side （P 〉 0.05）. CONCLUSION： BMSCs were successfully cultured in vitro, and the cells proliferated and trans-differentiated into neuronal-like cells, which expressed nestin and NSE. The FE-PLL complex effectively labeled rabbit BMSC-D-NSCs in vitro and did not affect peripheral neural regeneration following cell transplantation. Results demonstrated that MRI could be used to track FE-labeled BMSC-D-NSCs transplanted in the sciatic nerve.

Bifunctional staining for ex vivo determination of area at risk in rabbits with reperfused myocardial infarction

AIM: To develop a method for studying myocardial area at risk(AAR) in ischemic heart disease in correlation with cardiac magnetic resonance imaging(c MRI). METHODS: Nine rabbits were anesthetized, intubated and subjected to occlusion and reperfusion of the left circumflex coronary artery(LCx) to induce myocardial infarction(MI). ECG-triggered c MRI with delayed en-hancement was performed at 3.0 T. After euthanasia, the heart was excised with the LCx re-ligated. Bifunctional staining was performed by perfusing the aorta with a homemade red-iodized-oil(RIO) dye. The heart was then agar-embedded for ex vivo magnetic resonance imaging and sliced into 3 mm-sections. The AAR was defined by RIO-staining and digital radiography(DR). The perfusion density rate(PDR) was derived from DR for the AAR and normal myocardium. The MI was measured by in vivo delayed enhancement(i DE) and ex vivo delayed enhancement(e DE) c MRI. The AAR and MI were compared to validate the bifunctional straining for cardiac imaging research. Linear regression with Bland-Altman agreement, one way-ANOVA with Bonferroni's multiple comparison, and paired t tests were applied for statistics.RESULTS: All rabbits tolerated well the surgical procedure and subsequent c MRI sessions. The openchest occlusion and close-chest reperfusion of the LCx, double suture method and bifunctional staining were successfully applied in all animals. The percentage MI volumes globally(n = 6) and by slice(n = 25) were 36.59% ± 13.68% and 32.88% ± 12.38% on i DE, and 35.41% ± 12.25% and 32.40% ± 12.34% on e DE. There were no significant differences for MI determination with excellent linear regression correspondence(r global = 0.89; r slice = 0.9) between i DE and e DE. The percentage AAR volumes globally(n = 6) and by slice(n = 25) were 44.82% ± 15.18% and 40.04% ± 13.64% with RIO-staining, and 44.74% ± 15.98% and 40.48% ± 13.26% by DR showing high correlation in linear regression analysis(r global = 0.99; r slice = 1.0). The mean differences of the two AAR measurements on BlandAltman were almost zero, indicating RIO-staining and DR were essentially equivalent or inter-replaceable. The AAR was significantly larger than MI both globally and slice-by-slice(P < 0.01). After correction with the background and the blank heart without bifunctional staining(n = 3), the PDR for the AAR and normal myocardium was 32% ± 15% and 35.5% ± 35%, respectively,which is significantly different(P < 0.001), suggesting that blood perfusion to the AAR probably by collateral circulation was only less than 10% of that in the normal myocardium.CONCLUSION: The myocardial area at risk in ischemic heart disease could be accurately determined postmortem by this novel bifunctional staining, which may substantially contribute to translational cardiac imaging research.

SPECT和PET评估冬眠心肌联合心脏磁共振成像测定左心室室壁厚度对缺血性心肌病患者预后的预测价值

目的:探讨门控^(99)Tc^(m)-甲氧基异丁基异腈(MIBI)单光子发射计算机断层成像(SPECT)和^(18)F-脱氧葡萄糖(FDG)正电子发射断层成像(PET)评估冬眠心肌联合心脏磁共振成像(CMR)测定左心室室壁厚度对缺血性心肌病患者预后的预测价值。方法:回顾性纳入2017年1月至2020年8月于首都医科大学附属北京安贞医院在2周内行门控SPECT、门控PET和CMR检查且诊断为缺血性心肌病的患者75例。图像分析采用17节段法和5分法来评估心肌对显像剂的摄取情况(0分为正常,1分为轻度减低,2分为中度减低,3分为重度减低,4分为缺损),分别获得心肌灌注和心肌代谢异常的总积分,计算二者差值,灌注异常分-代谢异常分≥1分,即心肌灌注-代谢“不匹配”,定义为冬眠心肌。CMR测定的左心室舒张末期室壁厚度<4 mm的心肌节段定义为极薄心肌。根据冬眠心肌范围(冬眠心肌节段占左心室面积的百分比)和极薄心肌节段数,将患者分为四组:A组(冬眠心肌范围≤10%、极薄心肌节段数<2个)、B组(冬眠心肌范围≤10%、极薄心肌节段数≥2个)、C组(冬眠心肌范围>10%、极薄心肌节段数<2个)、D组(冬眠心肌范围>10%、极薄心肌节段数≥2个)。随访终点为全因死亡。采用Cox单因素和多因素模型分析全因死亡的独立危险因素,通过Kaplan-Meier法获得生存曲线,用log-rank检验比较生存率差异。结果:75例患者的平均年龄为(57±10)岁,男性69例(92.0%)。根据冬眠心肌范围和极薄心肌节段数区分,A组、B组、C组、D组分别有13例(17.3%)、14例(18.7%)、21例(28.0%)、27例(36.0%)。中位随访31.0(22.9,37.1)个月,11例(14.7%)患者死亡,A组、B组、C组、D组的累积生存率分别为(100±0)%、(100±0)%、(84.0±8.6)%、(63.5±12.2)%,组间差异有统计学意义(log-rankχ^(2)=9.788,P=0.02)。多因素Cox回归分析显示,冬眠心肌范围联合极薄心肌节段数是预测全因死亡的独立危险因素(HR=3.578,95%CI:1.236~10.356,P=0.019)。结论:SPECT和PET评估冬眠心肌联合CMR测定左心室室壁厚度可改善对缺血性心肌病患者的危险分层。

兔VX2肝癌模型的影像学表现和栓塞技术的实验研究

目的建立兔VX2肝癌模型,探讨其影像学表现和介入栓塞技术。方法将VX2瘤组织块种植于30只新西兰大白兔肝左叶,建立兔肝癌模型。行DSA前,将种植成功的兔子进行CT、MR检查,不同剂量碘油栓塞术后CT复查并观察各组生存情况。结果经剖腹探查证实肝脏种植成功24只(成功率80%,24/30);肝种植两周后CT平扫肿瘤多呈等或低密度区,增强扫描动脉期表现为边缘环状强化;MRI上肿瘤实质部分T1WI与T2WI分别表现为均匀低信号和稍高信号,DWI上瘤灶呈明显高信号,境界清晰,坏死部分呈长T1长T2信号影。DSA肝实质期可见肿瘤染色,栓塞时可见碘油在肿瘤部位充填、沉积,术后CT均能见瘤区有高密度碘油沉积,大部分为瘤周沉积。根据体重和超选择情况确定栓塞碘油剂量效果较好。结论兔肝VX2肿瘤模型的建立与复制成功率高。CT、MR和DSA有利于荷瘤兔的监测和筛选。暴露股动脉穿刺和用微导管超选择,可对肝脏荷瘤兔进行有效的选择性肝动脉造影和栓塞。

IDEAL-IQ定量评价兔糖尿病模型椎体骨髓脂肪含量的可行性研究

目的探索定量非对称回波的最小二乘估算法迭代水脂分离序列（iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation sequence,IDEAL-IQ）定量评估兔糖尿病模型椎体骨髓脂肪含量的可行性。材料与方法12只3月龄新西兰雄性大白兔随机分为糖尿病组（n=6）和对照组（n=6）。用四氧嘧啶对糖尿病组造模,在造模成功后各时间点（0、4、8、12、16周）,对糖尿病组及对照组行腰椎矢状位T1WI、T2WI、IDEAL-IQ检查。在IDEAL-IQ脂肪分数图像测量兴趣区内脂肪含量比值;在16周处死糖尿病组和对照组的大白兔,取腰3~7椎体做HE染色脂肪细胞计数;对实验组和对照组兔各时间点的脂肪含量比值采用重复测量的方差分析;对16周实验组和对照组IDEAL-IQ测量腰椎体脂肪比参数与HE切片镜下脂肪细胞计数行Pearson相关分析。结果16周实验组兔腰椎常规矢状位T1WI和T2WI显示诸腰椎椎体信号轻度增高。常规HE染色显示,16周糖尿病组兔椎体终板下骨髓腔脂肪含量较对照组明显增多,骨髓细胞明显减少。糖尿病组各时间节点椎体骨髓的脂肪含量比值差异存在统计学意义（F=50.387,P〈0.01）,对照组各时间点脂肪含量比值差异不存在统计学意义（F=1.477,P〉0.05）;16周实验组与对照组的椎体骨髓脂肪含量比值（FF%）差异有统计学意义（t=-10.726,P〈0.01）;IDEAL-IQ测量椎体脂肪含量比与脂肪细胞计数高度正相关关系（r=0.925,P〈0.05）。结论 IDEALIQ定量评估兔糖尿病模型椎体骨髓脂肪含量是可行的。.

MR弥散加权成像在兔脊柱结核早期诊断中的应用价值

目的探讨磁共振弥散加权成像(DWI)在兔脊柱结核发病早期的应用价值。方法选择健康成年新西兰白兔25只,应用外科手术建立兔脊柱结核动物模型,在手术后4、6、8周分别采用常规MRI及DWI扫描,观察MR表现并测量正常椎体与病变椎体的ADC值,采用方差分析,进行统计学分析。结果成功建立脊柱结核动物模型。脊柱结核动物模型术后第4、6、8周椎体及椎间盘形态未见明显异常,DWI出现异常信号,且病变椎体与正常椎体ADC值差别有统计学意义,病变椎体的ADC值高于正常椎体。结论 DWI分析及ADC值测量能够为脊柱结核早期诊断提供一定信息。

替罗非班联合尿激酶超选择动脉溶栓治疗急性大脑中动脉栓塞的实验研究

目的:探讨替罗非班联合尿激酶超选择性溶栓治疗急性大脑中动脉栓塞的疗效和安全性。方法:采用兔自体血栓栓塞大脑中动脉制成急性脑梗死模型,随机分为替罗非班组(T组)、尿激酶组(UK组)、替罗非班+尿激酶组(T+UK组)和对照组。采用X线数字减影(DSA)观察动脉内超选择溶栓的血管再通率,磁共振弥散成像观察相对表观弥散系数(rADC),改良Bederson评分法观察神经功能缺损。24h后处死动物,经氯化-2,3,5-三苯基四氯唑染色,进行光镜病理形态学检查。结果:T+UK组血管再通率为80%,病理检查未见明显出血,rADC值、神经功能缺损评分、脑梗死面积均优于T组、UK组和对照组。结论:早期使用替罗非班联合尿激酶进行动脉内溶栓在兔超早期脑缺血模型中疗效优于单纯尿激酶动脉内溶栓。

MRI评价兔VX2肝癌射频消融后改变:与病理对照

目的观察兔VX2肝癌射频消融(RFA)后的MRI动态变化,并与病理所见相对照,探讨MRI评价肝癌RFA疗效的价值。方法采用生理盐水与VX2瘤块混悬液注射法复制肝肿瘤动物模型24只。开腹直视下对24只兔肝癌进行RFA,并将其随机分为4组,分别于术后即刻、术后1周、2周和4周进行MR平扫及增强扫描检查;之后处死实验兔,进行大体病理和光镜检查。结果MRI表现为病灶T1WI中央低信号,外周高信号,T2WI中央高信号,外周低信号,增强扫描病灶外周环形强化,中央无强化。光镜下消融灶呈凝固性坏死,术后即刻组外周见少许中性粒细胞、巨噬细胞浸润,肝窦扩张充血;术后1周组外周见炎性细胞浸润及少许纤维肉芽组织增生;MRI表现为病灶T1WI呈稍低信号,T2WI呈稍高信号,增强扫描病灶周边呈环状强化,中央无强化。术后2周组外周见淋巴细胞、浆细胞、多核巨细胞浸润及梭形纤维组织增生;MRI表现为病灶T1WI稍低信号,T2WI混杂信号影,向外为等低信号包膜,增强扫描病灶周边环状强化,中央无强化。术后4周组外周见大量纤维肉芽组织增生;MRI表现为病灶T1WI低信号,T2WI由内向外呈低信号-稍高信号-线状高信号环,增强扫描病灶周边环状强化,中央无强化。本组实验中17只实验兔病理学发现有肿瘤残留,MRI表现为T1WI稍低信号,T2WI高信号,增强扫描呈结节状或厚度不均的环状强化。结论MRI可全面评价RFA后病灶的变化,及时发现肝癌残存与复发。

改良兔大脑中动脉阻塞模型的建立

目的:探讨简单、实用的兔大脑中动脉阻塞(MCAO)模型建立方法。方法:20只新西兰大白兔,随机分 为实验组(16只)和对照组(4只),实验组电凝阻断右侧大脑中动脉,并于术前及术后4h、8h和12h监测动脉血 pO2、pCO2、pH、血糖和体温,对照组仅暴露右侧大脑中动脉而不予电凝。对照组动物在术后4h和12hDWI检查后 处死,实验组在术后1h、4h、8h和12h进行DWI检查后处死,取兔脑组织进行HE染色光镜观察。结果:实验组 术前及术后各时点动脉血pO2、pCO2、pH、血糖和体温差异无统计学意义(P>0.05)。对照组DWI扫描未发现异常, 实验组MCAO后1hDWI右侧基底节和顶叶皮层均显示异常高信号,随时间延长,异常高信号区逐渐增大。实验 组MCAO后1h光镜下未见明显改变,4h光镜下可见神经元细胞核固缩,8h出现间质水肿,12h可见神经细胞坏 死。结论:电凝法制备兔MCAO模型是一种较为理想的方法。

CT引导下经皮纤维环穿刺建立兔腰椎间盘退变模型

目的：在CT引导下经皮纤维环穿刺建立兔腰椎间盘退变模型，并通过影像学和病理学验证其退变过程及效果。方法：3月龄新西兰大白兔18只，体重2.7~3.3kg，雌雄不限，术前均行X线及MRI检查。每只兔在螺旋CT引导下，用18G穿刺针经侧方皮下穿刺兔L5/6椎间盘（穿刺组），确认刺入椎间盘纤维环深度约为5mm，并对L4/5椎间盘进行假性穿刺（穿刺达椎间盘边缘，但不刺入纤维环内；假穿刺组），L3/4椎间盘作为对照椎间盘（对照组）。术后4周、8周、12周随机选取6只兔行X线片及MRI检查，观察各组椎间隙高度、邻近骨质改变及椎间盘信号改变，以“术后椎间隙高度/术前椎间隙高度×100”计算椎间盘高度相对值（DHRV），并进行椎间盘改良Thompson分级法分级；X线片及MRI检查结束24h内处死动物，选取对照、假穿刺和穿刺组椎间盘进行组织形态学及免疫组织化学分析。结果：对照组及假穿刺组术后4、8、12周，X线片示椎间隙高度无降低，无终板骨质硬化与骨赘形成；MRI T2加权成像图像示各椎间盘均呈高信号；组织学检查见髓核细胞数量较多，分布均匀，纤维环排列呈同心圆层状；免疫组化分析髓核呈Ⅰ型胶原染色强阳性，Ⅱ型胶原染色阴性，在各时间点表现无明显差别。穿刺组椎间盘在术后4周X线片即可见椎间隙高度轻度降低（DHRV=70.78±4.55），MRI示椎间盘信号强度轻度下降，组织学上见纤维环结构紊乱、髓核细胞轻度减少；术后8周椎间隙高度明显降低（DHRV=50.63±4.04），开始出现终板骨质硬化，MRI示椎间盘信号强度明显下降，组织学上髓核被胶原组织分裂为含较多椭圆形细胞的细胞岛，出现纤维软骨细胞，纤维环层状结构变形、部分断裂；术后12周椎间隙高度继续下降（DHRV=44.78±2.61），骨赘形成、终板骨质硬化明显，MRI示椎间盘信号强度继续减弱，组织学上见髓核被纤维软骨组织所代替，纤维环层状组织碎裂、解体；免疫组织化学分析示术后4、8、12周髓核Ⅰ型胶原染色逐渐增强，Ⅱ型胶原染色逐渐减弱。各时间点对照组椎间盘的DHRV及改良Thompson分级与假穿刺组比较均无统计学差异（P＞0.05）；穿刺组在术后不同时间点的DHRV降低、改良Thompson分级增高与对照组及假穿刺组比较均有统计学差异（P〈0.05）；随着穿刺时间的延长，穿刺组DHRV呈进行性降低趋势，改良Thompson分级进行性升高，两者在术后4、8、12周间均有统计学差异（P〈0.05）。结论：CT引导下经皮纤维环穿刺法诱导兔椎间盘退变模型构建成功，操作方法简单、创伤小，经影像学及病理学证实其退变过程为渐进性。

兔颈动脉粥样硬化模型的建立及MR成像的实验研究

目的建立兔血管内膜损伤性颈动脉粥样硬化模型,并探讨用临床应用型MRI检测动脉粥样硬化的形成过程。方法用动脉球囊介入扩张兔一侧颈总动脉后高脂饲养12周,分别在球囊扩张前及扩张后2、4、8、12周末取外周血检测血脂水平并MRI检查;同时在球囊扩张后12h、6周、12周末取损伤血管进行病理学检查。结果高脂喂养后第2周开始,血脂水平进行性升高;球囊扩张后6周起MRI显示,患侧均出现不同程度的血管壁高信号,12周后,MRI表现为损伤血管壁高信号区增厚并管腔狭窄,对应病理学检查显示:到第6周时,血管平滑肌层增厚,内膜面有少量泡沫细胞形成,血管腔轻度狭窄;12周后,损伤侧颈总动脉明显粥样斑块形成,符合动脉粥样硬化特点。结论用介入动脉球囊扩张损伤加高脂饲养方法可成功建立兔颈动脉粥样硬化狭窄模型,临床应用型MRI可成功检测兔颈动脉粥样硬化的形成过程。

三维对比增强MRA:新型血池型对比剂USPIO与Gd-DTPA对比实验研究

目的将自行研发的USPIO用于动物行3DCE-MRA,并与Gd-DTPA增强MRA比较,评估USPIO增强MRA成像质量,为其临床应用提供实验证据。方法14只健康雄性新西兰大白兔随机分为两组分别给予USPIO和Gd-DTPA行3D-CEMRA扫描,1周后,待对比剂完全排泄,两组交换行相应对比剂增强扫描。所有扫描在1.5T磁共振扫描仪上完成,采用Cardiac线圈,行3DSPGR序列冠位扫描。使用高压注射器由耳缘静脉注入对比剂。给药前扫描1次观察扫描范围(蒙片),打药同时开始行扫描,共连续扫描9个时相,再分别于5、10、15、20、25、30min重复扫描1次。USPIO使用剂量为0.1mmol/kg体重,Gd-DTPA为0.5mmol/kg体重。结果所有动物均能顺利完成扫描,图像质量显示清楚,通常在第2个时相可得到较好动脉期时相。USPIO和Gd-DTPA均可得到明显的血管增强效果。SI主动脉(t)曲线显示USPIO在血管内信号强度达峰时间与Gd-DTPA相似,但持续时间比后者长,峰值信号强度弱于后者(P<0.05)。SNR(t)和CNR(t)曲线显示,USPIO与Gd-DTPA有交叉,但峰值相近,在后期(10min后)USPIO明显高于Gd-DTPA(P<0.05)。两种对比剂对主动脉及其一级分支显示率并无统计学差异(P>0.05)。在USPIO增强较晚时期,实验动物的静脉及门脉显示较Gd-DTPA增强同时期更加清楚。结论USPIO在安全性,采集时间窗以及可同时动静脉,门脉显影上优于Gd-DT-PA,更适于用作CE-MRA。自制USPIO作为血管对比增强剂具有良好的显像效果。

磁共振扩散加权成像在家兔肝纤维化分期的诊断价值

目的探讨磁共振扩散加权成像（MR-DWI）在家兔肝纤维化（HF）分期中的价值。材料与方法将60只健康新西兰大白兔随机分为HF组（32只）、对照组（16只）和补充组（12只）。HF组和补充组兔经颈背部皮下注射50%的CCl4油溶液建立肝纤维化模型。在造模过程中,如HF组兔出现死亡,由补充组兔随机补充。HF组按预实验结果在注射CCl4后第4、5、6、10周末分别选HF组兔8只、对照组兔4只进行肝脏MRI常规轴位T1WI、T2WI序列及轴位DWI序列扫描,扫描完成后立即处死,进行病理学分期。DWI采用SE-EPI序列（b=50 s/mm2、400 s/mm2、800 s/mm2）,在ADC图上测量表观扩散系数（ADC值）。以组织病理学分期为标准,评价第4、5、6、10周ADC值与HF病理分期的相关性,并采用ROC曲线分析ADC值的诊断准确性。结果不同HF病理分期之间ADC值存在明显差异（F=5.344,P〈0.005）。随着肝纤维化的进展,肝脏实质平均ADC值相应降低;S0组和S1~S2组的ADC值均高于S3~S4组（P〈0.05）,S0组与S1~S2组的ADC值之间均无显著差异（P〉0.05）。ADC值与HF分期存在明显的相关性（r=-0.630,P〈0.001）但是S0、S1和S2三者之间以及S3和S4之间ADC值无明显差异（P〉0.1）。但相邻各组间ADC值重叠较大。结论 MR-DWI序列作为一种安全、可靠的无创性扫描技术,可为临床随访和疗效观察提供一种重要的补充手段。