【作者】 邢伟；

【导师】 田建明； 陆建平； 左长京； 王莉； 刘崎；

【作者基本信息】 第二军医大学 ， 影像医学与核医学， 2010， 博士

【摘要】 一、研究目的1、通过比较动物模型良恶性淋巴结的ADC值、rADC值评价MRI扩散成像鉴别良恶性淋巴结的能力。2、通过比较DWI及PET两者对良恶性淋巴结鉴别能力,评价扩散成像在临床应用的价值。3、通过测量动物淋巴结模型放疗前后ADC值的变化,结合病理学结果,评价扩散成像在评价淋巴结放疗疗效中的价值。4、通过测量临床鼻咽癌转移性淋巴结放疗前后ADC值,验证扩散成像对放疗疗效评价的能力。二、研究内容第一部分良恶性淋巴结MRI扩散成像的动物研究建立转移性淋巴结及炎性淋巴结动物模型,通过MRI常规检查测量两组淋巴结的形态学指标,包括淋巴结的最短径,淋巴结的边界(光滑、分叶或模糊)及淋巴结内坏死情况；MRI DWI检查测量淋巴结的ADC值,并以肌肉的ADC值为参照计算rADC值,比较两者鉴别良恶性淋巴结的价值。第二部分良恶性淋巴结鉴别的比较影像学研究建立转移性淋巴结及炎性淋巴结动物模型,分别行MRI扩散成像及双期PET检查,分别测量良恶性淋巴结的ADC值、rADC值、早期SUV值及延迟SUV值。ROC曲线分析四组数据鉴别良恶性淋巴结的能力。第三部分扩散成像对转移性淋巴结放疗疗效评价的价值研究建立转移性淋巴结动物模型,将其分为治疗组及对照组,治疗组接受放射治疗。分别于放疗前、放疗后第1、3、7天行MRI常规及DWI检查,测量淋巴结的大小、ADC值,比较两组之间的差异,评价放疗后淋巴结ADC值变化规律与对照组之间的差异。治疗组兔子分别于放疗后第1、3天每天各处死一只兔子,剩余兔子在第7天全部处死,取被测淋巴结行病理学检查,探讨放疗后ADC值变化与淋巴结病理改变之间的相关性。第四部分扩散成像评价颈部转移性淋巴结放疗疗效的临床研究通过随访鼻咽癌治疗后淋巴结大小的改变,将其分为有效组及无效组。所有患者行MRI及扩散成像检查,测量颈部转移淋巴结治疗前、治疗后第7天、第14天扩散成像ADC值的变化。利用重复测量分析评价各时间点ADC值的变化,探讨扩散成像评价疗效的可能性。三、研究结果第一部分16枚转移淋巴结最短径8.96±1.67mm,10枚炎性淋巴结最短径7.23±0.66mm,两者没有明显的统计学差异(P=0.005)。两组淋巴结均境界清楚,T1WI等信号,T2WI稍高信号。8枚转移性淋巴结内可见坏死,其中1枚完全囊变；10枚炎性淋巴结内未见明显坏死高信号。两组淋巴结实质部分DWI上均呈高信号,ADC图呈低信号；坏死区在DWI呈低信号,ADC图上为高信号。低b值条件下(0～500 s/mm2)良恶性淋巴结的ADC值及rADC没有明显统计学差异；高b值条件下(0～1000 s/mm2)良恶性淋巴结的ADC值及rADC值均有统计学差异。ROC曲线分析高b值组良恶性淋巴结ADC值ROC曲线下面积(AUC)为0.817,阈值0.88×10-3mm2/s,敏感性86.67%,特异性为80%；rADC值AUC为0.973,阈值为0.640,敏感性93.33%,特异性90%。第二部分两组淋巴结均境界清楚,T1WI等信号,T2WI稍高信号。3枚转移性淋巴结内可见坏死；9枚炎性淋巴结内信号均匀。淋巴结实质部分DWI上均呈高信号,ADC图呈低信号；坏死区在DWI呈低信号,ADC图上为高信号。良恶性淋巴结的ADC值及rADC值之间均有统计学差异。恶性淋巴结的SUVearly值及SUVdelay值明显大于良恶性淋巴结,良恶性淋巴结之间存在统计学差异。四者进行ROC曲线下分析,ADC值与rADC值之间存在差异,其余均未见明显统计学差异。第三部分放疗前1天,淋巴结体积在56.12～103.22mm2。淋巴结T1WI等信号、T2WI高信号。10枚淋巴结内可见坏死,其中治疗组8枚,对照组2枚。治疗组4枚淋巴结第7天信号开始不均匀,在淋巴结实质内出现小斑片状长T1长T2信号；对照组淋巴结信号未见明显改变。两组放疗前后各对应时间点淋巴结体积未见明显差异。放疗前、放疗后第1、3天两组淋巴结ADC值未见明显差异,放疗后第7天两组淋巴结的ADC值之间存在统计学差异。重复测量分析显示两组重复测量的结果之间存在明显差异(P=0.000)。放疗后第1天,治疗组淋巴ADC值轻度降低,与放疗前没有明显统计学差异。放疗后第3天开始,治疗组淋巴结ADC值明显升高,与放疗前及放疗后第1天ADC值有统计学差异。对照组放疗前后各时间点ADC值未见明显统计学差异。第四部分放疗前24例患者共发现75枚淋巴结。放疗结束后第4周,有效组共68枚淋巴结,其中51枚淋巴结完全消失,7枚淋巴结达到部分有效,7枚淋巴结病灶稳定。无效组共10枚淋巴结。24例患者中12例为左侧淋巴结转移,6例为右侧淋巴结转移,6例为双侧颈部淋巴结转移。治疗前及治疗后第7天两组淋巴结T1WI呈等信号,T2WI稍高信号,增强后淋巴结可见强化。治疗后第14天7枚淋巴结内可见少许坏死灶。两组淋巴结DWI呈高信号,ADC呈低信号。有效组及无效组放疗前及放疗第7、14天淋巴结体积存在明显差异。放疗前有效组及无效组淋巴结的ADC值未见明显差异(t=0.582,P=0.562)；放疗第7天及第14天两组淋巴结ADC值存在统计学差异(t=-2.219,P=0.30；t=-2.597,P=0.011)。重复测量分析显示重复测量的结果之间存在高度相关性(P=0.000),测量指标有随时间变化的趋势并且时间因素的作用随着分组不同而不同。有效组各时间点ADC值逐渐升高,彼此之间有明显的差异；无效组第14天ADC值与治疗前及治疗后第7天有明显差异(P=0.004,P=0.013)。四、研究结论1、高b值较低b值能更好的区分良恶性淋巴结。恶性淋巴结的ADC值及rADC值明显高于良性淋巴结。rADC值能较ADC值更好的区分良恶性。2、扩散成像能够有效的区分良恶性淋巴结,与PET成像效果相似。其中rADC值诊断能力优于ADC值。扩散成像是诊断良恶性淋巴结的有效方法,在临床有重要的应用价值。3、扩散成像能够早期间接反应组织放疗后的改变,对于监测淋巴结的疗效有一定帮助。4、鼻咽癌颈部转移性淋巴结治疗后,扩散成像能反应早期各时间点有效组及无效组之间的差异,对于疗效的监测有一定帮助。更多还原

【Abstract】 1. BackgroundLymph node metastasis is a most common malignant tumor migration path, through the imaging evaluation of the nature of lymph node lesions is conducive to the development and prognosis of treatment options. MRI technology, with its excellent soft tissue resolution, can identify the quality of lymph nodes diseases more accurately than CT and ultrasound. But the signal intensity on Tl-weighted imaging and T2-weighted imaging of benign and malignant lymph nodes have some overlaps in conventional MRI, and can not determine the nature of the lymph nodes based on them. Up to now, conventional imaging techniques play important roles in assessment of the lymph node status, which rely on lymph node morphology such as shape, size, necrosis and extracapsular spread. The shortest axis of malignant lesions is larger than 1cm and the shape is similarly round. Conversely, the shortest axis of benign lesions is smaller than 1 cm and the shape is oval, in which the ratio of large and short axis is approximately 2. Necrosis of malignant lymph nodes is more common, and often shows extracapsular spread. However, many studies have found that these criteria can not completely distinguish benign from malignant lymph nodes, especially for small lymph node lesions, in which may already exist micro-metastases, meanwhile morphological diagnosis becomes lagging.With the development of radiological imaging technology, the functional imaging technologies are used to reveal the functional changes in different way. MRI diffusion-weighted imaging can reveal micro-movement of water molecules in vivo, and is used to detecte early physiological and functional changes related to tissue water content. A few researches are mainly concentrated in cervical lymph nodes. Razek et al. found that diffusion-weighted imaging can found lesions with the smallest diameter of 0.9cm, while the malignant nodules ADC value are lower than benign nodules. Sumi etc al. found that ADC values of cervical lymph node metastasis were significantly higher than benign lymph node lesions. Although DWI can be more sensitive and more accurate to diagnosis, the results between different studies had some differences. DWI imaging is a potent technology with short examination time, non-invasive, no radiation, and no injection of contrast agents, so a comprehensive and systematic evaluation of DWI in the diagnosis and treatment of benign and malignant lymph nodes plays an important role in its clinical practice.2. Objectives1. To evaluate the value of ADC values and relative ADC values in the differentiation of benign and malignant lymph nodes in animal models with MRI diffusion-weighted. imaging, and estimate its clinical application value by comparison with PET imaging.2. To analysis of the value of diffusion-weighted imaging and PET in discrimination of benign and malignant lymph nodes by compared of the ADC values, relative values, early SUV and delayed SUV.3. To evaluate the value of DWI in assessment of radiation effect by comparison with pre-and pro-radiation ADC values of lymph nodes, combined with pathological results.4. To collect ADC values of metastatic lymph node in patients before and after irradiation, and verify the value of DWI in assessment of radiation effect.3. Material and methodsPart I Value of MRI diffusion-weighted imaging in the differential diagnosis of benign and malignant lymph nodesTwo groups of animal models, including metastatic lymph node and inflammatory lymph nodes, were established. Some morphological indicators of lymph nodes were measured in conventional MRI, including shortest diameter, border (smooth, lobulated or indistinct), and necrosis. ADC values of lymph nodes also were measured in MRI DWI. The contralateral quadriceps femoris was selected as the reference site for rADC values. rADC was calculated by ADCiesion/ADCreference site.The benefit of rADC over ADC was validated for identifying metastatic lymph nodes. SUVs of benign and malignant lymph nodes of PET were measured. By comparing the values between ADC values and SUVs in identifying the nature of lymph nodes, the clinical value of DWI was evaluated.PartⅡStudy of different imaging methods in discrimination of benign and malignant lymph nodesThe animal models of metastatic lymph node and inflammatory lymph nodes were established respectively. MRI diffusion-weighted imaging and dual-phase PET examination were both made. All ADC values, rADC values and the value of early and delayed SUV of benign and malignant lymph nodes were measured. ROC curve analysis was made to evaluate the ability of four sets of data to identify benign and malignant lymph nodes.PartⅢValue of DWI in evaluation of metastatic lymph nodes response to radiation therapyThe animal models of metastatic lymph nodes were established. Then they were divided into control group and therapy group. And the therapy group received radiotherapy. MRI and DWI were performed respectively pretreatment,1,3,7 days after radiotherapy. The volumns of lymph nodes and ADC values were measured. The difference between the two groups was compared. In 1 day and 3days, one rabbit were sacrificed every day. The remaining rabbits in 7 days all were killed. Correlation between pathological changes and ADC values of lymph nodes after radiotherapy was explored.PartⅣMR diffusion-weighted imaging for evaluation of therapeutic responds in neck metastastic lymph nodesBy follow-up of nasopharyngeal carcinoma, according to the size of lymph nodes, all patients were divided into an effective group and an ineffective group. All patients were examined with MRI and diffusion imaging. The ADC values of cervical metastastic lymph nodes were measured before treatment and the 7th and 14th days after treatment. Repeated measures analysis was made to evaluate ADC values at different time points, and to explore the possibility of diffusion-weighted imaging in predicting therapeutic effect. 4. ResultsPart I The mean shortest diameter of 16 metastatic lymph nodes was 8.96±1.67mm, and of inflammatory lymph nodes was 7.23±0.66mm, that there is no statistically significant difference (P= 0.005). Two groups of lymph nodes were clear boundary, and iso-intensity on T1WI and slight hyperintensity on T2WI. Necrosis was observed in eight metastatic lymph nodes, in which one is an entirely cysti. There was no necrosis in the ten inflammatory lymph nodes. All lymph nodes were hyperintensity in DWIs, hypointensity in ADC maps; necrotic areas in DWI showed low signal, hyperintensity in ADC maps. Under the conditions of the low b values (0～500s/mm2), the ADC and rADC value between benign and malignant lymph nodes had no significant statistical difference; under conditions of high b values (0～1000s/mm2), the ADC and rADC value between benign and malignant lymph nodes had statistically difference. ROC curve analysis of benign and malignant lymph nodes was made. The area under the ROC curve (AUC) of ADC value was 0.817. When the threshold was 0.88×10-3mm2/s, the sensitivity was 86.67%and the specificity was 80%. The AUC of rADC value was 0.973. When the threshold value was 0.640, the sensitivity was 93.33%and the specificity was 90%.Part II The boundaries of all lymph nodes were clear. They are iso-intensity on T1WI and slightly hyperintensity on T2WI. Necrosis was seen in three metastatic lymph nodes. The signals of all inflammatory lymph nodes were homogenous. Parechymal parts of all lymph nodes revealed hyperintensity on DWI, and hypointensity on ADC maps. Necrotic areas showed hypointensity on DWI and hyperintensity on ADC maps. The ADC and rADC values were significant differences between two groups. SUVearly value and SUVdelay of malignant lymph nodes were significantly greater than those of benign nodes, and there was statistical difference. ROC curve analysis was done, and only ADC values and rADC values revealed statistical difference.PartⅢBefore treatment, the sizes of lymph node were from 56.12-103.22mm2. Lymph nodes were iso-intenstiy on TiWI and hyperintensity on T2WI. Necrosis was seen in ten lymph nodes, in which eight was belong to therapy group and two lay in control group. In 7 days after treatment, signals of four lymph nodes begun uneven. In control group, signals had no significant change. There were no significant differences between the two groups at each time point before and after radiotherapy in lymph node size. There were significant difference of ADC values between the third and seventh day after treatment and pretreatment and once day after treatment. Repeated measurements indicated significantly difference between the two groups. In the third day after radiotherapy, ADC values of the treatment group were significantly higher than before and the first day after treatment. The control group at all time points before and after radiotherapy revealed no significant difference in ADC values.PartIV Seventy-five lymph nodes were found in 24 patients before radiotherapy. After 4 weeks of the end of radiotherapy,51 lymph nodes in effective group completely disappeared, seven lymph nodes were partial response and seven lymph nodes were stable. A total of 10 lymph nodes were no response. Metastastic lymph nodes in 12 cases located in left necks,6 cases located in right necks, and 6 cases located in bilateral necks. All lymph nodes were iso-intensity on T1WI and hyperintensity on T2WI. After enhancement, all lymph nodes can be enhanced. The 14th days after treatment, within seven lymph nodes necrotic foci can be seen. Two groups of lymph nodes showed high signals on DWI,and low signals on ADC maps. There were significant difference between effective group and ineffective group before and after radiotherapy in lymph node sizes. There was no significant difference of ADC values between the effective group and ineffective group before (t=0.582, P=0.562), the 7th and 14th days after treatment(t=-2.219, P=0.30; t=-2.597, P=0.011). Effective group at each time point ADC values gradually increased, there were obvious differences between them; in ineffective group, ADC values in the 14th day after treatment revealed significant difference between before treatment and the 7th day after treatment (P=0.004, P=0.013).5. Conclusion1. DWI with high b value can better distinguish between benign and malignant lymph nodes than those with a low b values. The ADC values and rADC values of malignant lymph nodes were significantly higher than benign lymph nodes. rADC values can better distinguish between benign and malignant lymph nodes than the ADC value.2. DWI can effectively distinguish between benign and malignant lymph nodes, and is similar to PET imaging. rADC values are better than ADC values in diagnostic capabilities. DWI is an effective method and has important clinical value.3. DWI can reflect response indirectly of foci early after radiotherapy, and help to monitor radiation efficacy of lymph nodes.4. After treatment in nasopharyngeal carcinoma metastatic cervical lymph nodes, diffusion imaging can reflect differences between effective and ineffective group at different time points of early response. And it is useful to monitor the treatment responds.更多还原