【作者】 徐贤；

【导师】 张金山； 马林；

【作者基本信息】 中国人民解放军军医进修学院 ， 影像医学与核医学， 2009， 博士

【摘要】 第一部分健康成人骨髓的全身磁共振弥散加权成像研究目的:探讨健康成人骨髓全身磁共振弥散加权成像（Whole Body DiffusionWeighted Imaging,WB-DWI）定量参数与性别、年龄、身高、体重、体重指数及性激素水平的相关性,为建立不同性别各年龄组的正常WB-DWI定量指标提供参考范围。材料和方法:纳入108例不同年龄组的健康志愿者,其中男性53例,女性55例,年龄范围20～80岁,平均年龄49.45岁。用GE1.5T磁共振扫描仪对受试者进行WB-DWI扫描,对其中60例健康受试者在接受扫描的前/后48小时内测量雌二醇及孕酮水平。测量受试者颈7、胸8、腰4及双侧髂骨的ADC值和SNR值,取平均值。将108例健康志愿者按年龄分为青年组（18～39岁）、中年组（40～59岁）、老年组（60～80岁）,比较不同性别、不同年龄组受试者骨骼系统ADC值和SNR值的差异。采用偏相关分析评估60例受试者骨骼系统ADC值和SNR值与性别、年龄、身高、体重、体重指数、雌二醇及孕酮水平的相关性。结果:女性受试者骨骼系统的ADC值和SNR值显著高于男性（P＜0.01）;不同年龄组骨骼系统的ADC值和SNR值存在显著性差异（P＜0.01）。骨骼系统ADC值与身高、体重、体重指数无显著相关性（P＞0.05）,与年龄呈显著负相关（r=-0.642,P＜0.01）,与雌二醇、孕酮水平呈轻度正相关（r=0.278,P=0.04;r=0.271,P=0.045）。骨骼系统SNR值与身高、体重、体重指数、孕酮无显著相关性（P＞0.05）,与年龄呈显著负相关（r=-0.709,P＜0.01）,与雌二醇水平呈轻度正相关（r=0.293,P=0.03）。孕酮与雌二醇在对骨骼系统ADC值和SNR值的影响上具有协同作用（r=0.65,P＜0.01;r=0.573,P＜0.01）。结论:骨骼系统的ADC值和SNR值受到性别、年龄和性激素水平的影响,不同性别、年龄组骨骼系统的WB-DWI表现存在差异。了解健康成人骨骼系统正常WB-DWI表现对于准确判断骨骼系统疾病有着重要的意义。第二部分全身磁共振弥散加权成像在探测及鉴别骨恶性肿瘤的研究目的:通过与骨扫描对比,探讨全身弥散加权成像（WB-DWI）探测骨转移灶的效能;比较骨骼系统恶性肿瘤和感染性病变在DWI的差异。材料和方法:将45例有明确恶性肿瘤病史且怀疑合并骨转移的患者（男25例,女20例,年龄17～74岁,平均年龄52.7岁）行WB-DWI扫描及SPECT骨扫描,WB-DWI扫描采用GE3.0 T磁共振扫描仪。分别记录WB-DWI扫描及SPECT骨扫描探测病灶的数目,并比较两种检查手段探测病灶的敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）。对23例椎体转移患者和14例脊柱感染患者采用1.5T磁共振扫描仪进行WB-DWI检查,比较32处转移灶和19处感染灶的ADC值和对比噪声比（CNR）。结果45例患者中,WB-DWI共检出35例阳性患者,77处“受累”区域共181处病灶,而骨扫描阳性34例,有76处“受累”区域共167处病灶。两种方法检出阳性病例的敏感性和阳性预测值相似（89.5%vs.81.6%,97.1%vs.91.2%）,但WB-DWI的特异性和阴性预测值要高于骨扫描（85.7%vs.57.1%,60%vs.36.4%）。此外,WB-DWI的“区域”敏感性和特异性要稍高于骨扫描（89.5%vs.88.4%,95.6%vs.87.6%）。32处骨转移灶的平均ADC值和CNR值分别为0.963±0.150(×10^-3mm²/s)和27.417±4.819;19处骨感染灶的平均ADC值和CNR值分别为1.412±0.211(×10^-3mm²/s)和13.127±3.604。转移组的ADC值显著低于感染组,CNR值显著高于感染组（P＜0.01）。ADC值小于1.17×10^-3mm²/s时,诊断恶性病变的敏感性、特异性、阳性预测值、阴性预测值和准确度分别为93.8%,84.2%,90.9%,88.9%和90.2%。结论:WB-DWI与骨扫描在检测骨转移病灶中有很好的一致性,且两者可互相补充。DWI在鉴别骨骼良、恶性病灶中有着较重要的作用。第三部分全身磁共振弥散加权成像与PET-CT在淋巴瘤的初步对比研究目的:通过与PET-CT对比,探讨WB-DWI技术在淋巴瘤临床分期的应用价值。材料和方法:将12例初治或治疗后复发淋巴瘤患者进行全身DWI-FIESTA和PET-CT检查,其中男9例,女3例,年龄24～85岁,平均46.67岁。两种检查间隔时间小于10天,期间均未行正规临床治疗。采用思创（CREALIFE）公司的ST-PACS型GVCM软件V3.1版本对WB-DWI图像和FIESTA图像进行融合,形成DWI-FIESTA图像,比较PET-CT和DWI-FIESTA对12例淋巴瘤患者的临床分期,并分别记录全身DWI-FIESTA及PET-CT探测病灶的数目。对75个区域的病灶分别测量SUV值和ADC值,采用Spearsman等级相关分析淋巴瘤病变的SUV值和ADC值的相关性。结果:PET-CT和WB-DWI对12例患者的临床分期均一致,两种检测方法的一致性为100%。PET-CT共检出12例患者的87处病灶,WB-DWI检出了85处病灶,有两处假阴性病灶。以PET-CT为金标准,WB-DWI检出病灶的敏感性和特异性分别为97.7%和100%;统计学分析提示两种检查方法对病灶检出无显著性差异（P＞0.05）。75个区域病灶的SUV值为5.156±4.452,ADC值为0.884±0.214(×10^-3mm²/s),经统计学检验,淋巴瘤病灶的SUV值和ADC值无显著相关性（r=-0.120,P=0.306）。结论:WB-DWI与PET-CT对淋巴瘤的临床分期和病灶检出率相仿,对指导和监测临床治疗有着重要的价值;PET与DWI检出淋巴瘤病灶的原理不同,SUV值与ADC值无明确相关性。第四部分全身磁共振弥散加权成像对淋巴瘤的增殖活性、恶性程度和预后的评估目的:通过分析淋巴瘤ADC值与Ki-67指数、侵袭性和国际预后指数的关系,探讨WB-DWI评估淋巴瘤的增殖活性、恶性程度和预后的价值。材料和方法:对30例初治或复发淋巴瘤患者行WB-DWI检查,其中男17例,女13例,年龄19～85岁,平均45.73岁,测量手术或活检标本区病灶的ADC值。采用通用型SP-9000免疫组化试剂盒测量肿瘤Ki-67指数,将阳性细胞百分率＜25%定为低表达组,25-75%为中表达组,＞75%为高表达组,采用方差分析比较Ki-67高表达、中表达和低表达组ADC值的差异。按照2000年WHO淋巴瘤分类将患者分为霍奇金组、惰性非霍奇金组、侵袭性非霍奇金组和高侵袭非霍奇金组,采用方差分析比较各组ADC值的差别。根据NHL的国际预后指数（IPI）将患者分为低危组（0～1分）、低中危组（2分）、中高危组（3分）和高危组（4～5分）,比较各组间ADC值的差别。结果:30例淋巴瘤患者中,Ki-67低表达组9例,ADC值为1.019±0.149(×10^-3mm²/s);中表达组13例,ADC值为0.828±0.164(×10^-3mm²/s);高表达组8例,ADC值为0.625±0.105(×10^-3mm²/s),。低表达组的ADC值显著高于中表达组（P＜0.01）;中表达组的ADC值显著高于高表达组（P＜0.01）。本研究中霍奇金淋巴瘤6例,惰性淋巴瘤4例,侵袭性淋巴瘤16例,高侵袭性淋巴瘤4例。霍奇金淋巴瘤的ADC值显著高于侵袭性淋巴瘤和高侵袭性淋巴瘤（P＜0.01）,与惰性淋巴瘤的ADC值无显著差异（P＞0.05）;惰性淋巴瘤的ADC值显著高于侵袭性淋巴瘤和高侵袭性淋巴瘤（P＜0.01）;侵袭性淋巴瘤的ADC值稍高于高侵袭性淋巴瘤（P＜0.05）。按照国际预后指数分类,低危组10例,低中危组6例,中高危组9例,高危组5例,各组间的ADC值无显著差异（P=0.1436）。结论:淋巴瘤的ADC值在一定程度上可以反映肿瘤的增殖活性,肿瘤增殖活性越强,ADC值越低;淋巴瘤的ADC值与其侵袭性相关,即肿瘤侵袭性越强,ADC值越低;淋巴瘤ADC值与IPI指数之间无明确相关性。更多还原

【Abstract】 PartⅠ:Whole Body Diffusion Weighted Imaging on Normal Bone MarrowObjective:To evaluate the correlation between quantitive parameters of bone marrow DWI and gender,age,height,weight,BMI index and serum sex hormone levels and to estabalish the normal reference range.Methods:108 healthy volunteers（53 males and 55 female,age range 20～80 years, mean age 49.454 years） were enrolled in study.The whole body DWI examination was performed on GE Signa 1.5T MR scanner using embedded body coil.The serum estradiol（E2） and corporin were measured in 60 healthy subjects within 48h of MR examination.The ADC values and SNR values of the 7^th cervical spine,8^th thoracic spine,4^th lumbar spine and bilateral ilium were measured,and the average values were used.The 108 volunteers were classified as young-aged group（age range 18～39 years）,middle-aged group（age range 40～59 years） and old-aged group（age range 60～80 years）,the ADC and SNR values between genders and different age groups were compared.The partial correlation analysis was performed between ADC and SNR values and gender, age,height,weight,BMI index and serum sex hormone levels.Results:ADCs and SNRs of female subjects were significantly higher than those of male（P＜0.01）,and there were significant difference of ADCs and SNRs between different age groups（P＜0.01）.ADCs of bone marrow showed no statistical correlation with height,weight and BMI index（P＞0.05）,but had significant negative-correlation with age（r= -0.642,P＜0.01） and slightly statistical positive-correlation with serum E2 and corporin levels（r= 0.278,P =0.04;r=0.271,P=0.045）.SNRs of bone marrow showed no statistical correlation with height,weight,BMI index and corporin levels（P＞0.05）,but showed significant negative-correlation with age（r= -0.709,P＜0.01） and slightly statistical positive-correlation with serum E2 levels（r= 0.293,P=0.03）.Serum E2 and corporin showed synergistic effect on ADCs and SNRs of bone marrow（r= 0.65,P＜0.01;r=0.573,P＜0.01）.Conclusion:The ADCs and SNRs of bone marrow were influenced by gender, age and sex hormone levels,the variances of bone marrow DWI in different genders and age groups were observed.To understand the normal appearance of bone marrow DWI was valuable on confirming bone abnormality.PartⅡ:Efficacy of Whole Body Diffusion Weighted Imaging in Detecting and Differentiating Skeletal MaligancyObjective:To evaluate the efficacy of WB-DWI in bone metastasis detection using bone scintigraphy as comparison and to differentiate spinal infection and malignancy with DWI.Methods:Forty-five patients with malignancy history（20 males and 25 females, age range 17～74 years,mean age 52.7 years） were enrolled in our study.All the patients received WB-DWI on GE Signa 3.0T MR scanner and bone scintigraphy scan within 1 week.The images were reviewed separately by two radiologists and two nuclear medicine physicians,who were blinded to the results of the other imaging modality.The sensitivity,specificity,positive predictive value（PPV） and negative predictive value（NPV） were analyzed.Twenty-three patients with veterbral metastases and fourteen patients with spinal infection received WB-DWI on GE Signa 1.5T MR scanner.The ADC values and CNR values of the 32 metastastic lesions and 19 infectious lesions were compared.Results:A total of 181 metastatic lesions in 77 regions of 35 patients were detected by WB-DWI,and 167 metastatic lesions in 76 regions of 34 patients were identified by bone scintigraphy.The patient-based sensitivity and PPV of the WB-DWI and bone scintigraphy were similar（89.5%vs.81.6%,97.1%vs. 91.2%）,whereas,the patient-based specificity and NPV of WB-DWI were obviously higher than those of bone scintigraphy（85.7%vs.57.1%,60%vs. 36.4%）.The region-based sensitivity and specificity of WB-DWI were slightly higher than those of bone scintigraphy（89.5%vs.88.4%,95.6%vs.87.6%）.The mean ADCs and CNRs of metastasis were 0.963±0.150(×10^-3mm²/s) and 27.417±4.819,and those of infectious diseases were 1.412±0.211(×10^-3mm²/s) and 13.127±3.604 respectively.The ADCs of metastasis were significantly lower than those of infectious diseases,while CNRs of metastasis were significantly higher than those of infectious diseases（P＜0.01）.Using the threshold ADC value as 1.17×10^-3mm²/s,the sensitivity,specificity,PPV,NPV and accuracy were 93.8%,84.2%,90.9%,88.9%and 90.2%respectively.Conclusion:WB-DWI revealed excellent concordance with bone scintigraphy regarding detection of bone metastasis.DWI had important value for differentiating spinal infection and malignancy.PartⅢ:Comparison of Whole Body Diffusion Weighted Imaging and PET-CT on LymphomaObjective:To evaluate the application of WB-DWI on lymphoma using PET-CT as reference.Methods:12 patients（9 males and 3 females;age range 24～85 years,mean age 46.67 years） who suffered from initial or recurrent lymphoma were received whole body DWI-FIESTA and PET-CT examinations within 10 days and without clinical therapy between them.DWI and FIESTA images were confused as whole body DWI-FIESTA images using GVCM V3.1 software（CREALIFE Company）. The images were reviewed separately by two radiologists and two nuclear medicine physicians.The tumor stagings and "affected regions" of 12 patients by two methods were compared.SUV values and ADC values of 75 regions were measured,and correlation between them was analyzed using Spearsman rank test.Results:The consistency of WB-DWI and PET-CT on tumor staging was 100%. A total of 87 "affected regions" were detected by PET-CT while 85 regions by WB-DWI,the sensitivity and specificity of WB-DWI were 97.7%and 100% respectively when using PET-CT as reference.The two modalities showed no significant difference in detecting lesions（P＞0.05）.Mean SUVs of 75 regions was 5.156±4.452 and mean ADCs was 0.884±0.214(×10^-3mm²/s),there was no significant correlation between SUVs and ADCs（r= -0.120,P=0.306）.Conclusion:WB-DWI had important clinical value on tumor staging and lesion detection of lymphoma.There was no significant correlation between SUVs and ADCs because of different principles of the two methods. PartⅣ:The Study of Diffusion Weighted Imaging on Evaluating Proliferation,Invasion and Prognosis of LymphomaObjective:To study the value of DWI on evaluating the proliferation,invasion and prognosis of lymphoma.Methods:30 patients（17 males and 13 females,age range 19～85 years,mean age 45.73 years） with initial or recurrent lymphoma were performed WB-DWI examination.ADC values of surgery or biopsy regions were measured. Immunohistochemistry staining of Ki-67 was carried out to indicate tumor proliferation,and was classified as low expression group（＜25%）,middle expression group（25～75%） and high expression group（＞75%）.ADCs of different groups were compared.Patients were divided into Hodgkin’s lymphoma（HD）, inert non-hodgkin’s lymphoma（NHL）,aggressive NHL and highly aggressive NHL according to 2000 WHO classification and ADCs of these groups were compared.Patients were classified as low risk group（0～1 scores）,low-middle risk group（2 scores）,middle-high risk group（3 scores） and high risk group（4～5 scores） according to international prognosis index（IPI）,and the ADCs were compared between them.Results:There were significant difference between different expression groups of Ki-67（F=15.46,P＜0.01）.The ADC values of high expression group were significantly lower than those of middle expression group（0.625±0.105 vs 0.828±0.164,P＜0.01）,and the ADC values of middle expression group were significantly lower than those of low expression group（0.828±0.164 vs 1.019±0.149,P＜0.01）.The ADC values of four groups with different aggressiveness were significantly different（F=14.81,P＜0.01）,however,there was no significant difference between HD and inert NHL.There was no significant difference of ADC values between four groups with different IPI index（F=1.97,P=0.14）.Conclusion:The ADC values could reflect the proliferation and invasive potention of lymphoma to some extent,but had no statistical relationship with international Prognosis index.更多还原