本文選題：淋巴水腫 + 磁共振成像��； 參考：《上海交通大學(xué)》2014年博士論文

【摘要】：第一部分常規(guī)磁共振成像在淋巴系統(tǒng)相關(guān)疾病診斷中的應(yīng)用 目的：（1）探討常規(guī)磁共振成像在繼發(fā)性淋巴水腫診斷中的價值并評估其參數(shù)在淋巴水腫早期診斷以及分期中的應(yīng)用價值。 （2）探討DWI和FDG-PET（CT）在評估和預(yù)測直腸患者接受NCRT治療后病理反應(yīng)診斷的準(zhǔn)確性。 方法：（1）對72名婦科術(shù)后繼發(fā)單側(cè)下肢淋巴水腫患者以及22名婦科術(shù)后無明顯肢體水腫出現(xiàn)的患者進(jìn)行T1WI、T2WI、T2脂肪抑制序列以及磁共振水成像序列掃描，分析下肢淋巴水腫分期與患側(cè)大、小腿的直徑（TT）、相應(yīng)肌肉直徑（MT）、皮下軟組織厚度（STT）、患側(cè)與正常側(cè)大小腿直徑差值（DTT）、肌肉直徑差值（DMT）、皮下軟組織厚度差值（DSTT）間的相關(guān)性。 （2）通過數(shù)據(jù)庫文件檢索和篩選，最終入組33文獻(xiàn)并進(jìn)行meta-analysis，評價指標(biāo)包括敏感性、特異性、PPV以及NPV等。 結(jié)果：（1）淋巴水腫在常規(guī)磁共振圖像上表現(xiàn)有：真皮增厚；皮下組織增厚；網(wǎng)格狀改變；蜂窩狀改變；淋巴水腫基本不引起肌肉組織信號的改變。T2脂肪抑制序列可以消除脂肪信號干擾，因此T2脂肪抑制序列更有利于顯示淋巴水腫。磁共振水成像可以顯示呈囊樣、串珠樣擴(kuò)張的淋巴管、皮下積液程度和范圍以及水腫肢體的皮下網(wǎng)格狀改變。T2脂肪抑制序列參數(shù)中，患側(cè)大、小腿的TT、STT以及DTT、SDTT與淋巴水腫分期相關(guān)，但是MT則沒有相關(guān)性，其中小腿DSTT以及大腿DTT與淋巴水腫分期的相關(guān)性最好�；紓�(cè)小腿STT、DTT、DSTT以及大腿DTT在淋巴水腫不同分期間比較具有統(tǒng)計學(xué)差異（p值均小于0.05），其他參數(shù)沒有統(tǒng)計學(xué)差異。根據(jù)ROC曲線分析，小腿皮下軟組織厚度差值DSTT是評價淋巴水腫分期的最佳參數(shù)指標(biāo)。 （2）研究發(fā)現(xiàn)DWI敏感性和NPV高于PET或FDG PET-CT(p＜0.05)，而二者的特異性和PPV沒有差異（p＞0.05）。本研究沒有發(fā)現(xiàn)閾值效應(yīng)。元回歸分析表明DW-MRI及FDG PET (CT)盲法研究是診斷準(zhǔn)確性最重要的影響因素。 結(jié)論：本次研究表明常規(guī)磁共振成像可以用于輔助淋巴水腫的臨床診斷；小腿皮下軟組織厚度差值可以作為淋巴水腫患者早期診斷和水腫分期的指標(biāo)，幫助臨床選擇最佳的治療時機(jī)和治療方案。DWI在評估直腸癌患者接受NCRT治療的病理反應(yīng)方面優(yōu)于FDG PET (CT)。 第二部分磁共振淋巴造影在淋巴水腫相關(guān)疾病診斷中應(yīng)用價值 目的：探討磁共振淋巴造影成像在婦科腫瘤術(shù)后繼發(fā)下肢淋巴水腫以及腹股溝區(qū)淋巴管瘺診斷中的應(yīng)用價值。 方法：（1）對80名婦科腫瘤術(shù)后繼發(fā)下肢淋巴水腫患者進(jìn)行磁共振淋巴造影成像，，計數(shù)和測量患側(cè)大、小腿淋巴管數(shù)目、淋巴管最大徑并與正常側(cè)進(jìn)行比較，同時統(tǒng)計分析不同淋巴水腫分期間淋巴管數(shù)目及最大徑有無差別。 （2）對23名腹股溝區(qū)淋巴管瘺患者行磁共振淋巴造影成像檢查，評估其顯示淋巴管瘺成功率以及與淋巴結(jié)顯像差別，同時以瘺持續(xù)時間為據(jù)將病人分成2組后比較分析冠狀面淋巴管瘺的最大截面積、引流淋巴管的數(shù)目及最大徑間的差異。 結(jié)果：（1）婦科腫瘤術(shù)后繼發(fā)淋巴水腫患側(cè)小腿淋巴管數(shù)目多于正常側(cè)（p＜0.01）；而大腿患側(cè)、正常側(cè)淋巴管數(shù)目比較無顯著性差異（p＞0.05）；患側(cè)小腿淋巴管數(shù)目以及最大徑與患側(cè)大腿比較，均有顯著性差異（p＜0.01）�；紓�(cè)小腿淋巴管最大徑于淋巴水腫各分期組間比較發(fā)現(xiàn)，1期VS.2期以及2期VS.3期均無統(tǒng)計學(xué)差異，1期VS.3期有統(tǒng)計學(xué)差異。患側(cè)大腿各分期內(nèi)淋巴管最大徑比較無統(tǒng)計學(xué)差異（p＞0.05）�；紓�(cè)小腿淋巴管數(shù)目淋巴水腫各分期組間比較發(fā)現(xiàn)，1期VS.2期無統(tǒng)計學(xué)差異，2期VS.3期以及1期VS.3期有統(tǒng)計學(xué)差異（p值均小于0.05）�；紓�(cè)大腿各分期內(nèi)淋巴管數(shù)目中位數(shù)比較無統(tǒng)計學(xué)差異（p＞0.05）。所有水腫側(cè)下肢一共發(fā)現(xiàn)淋巴反流56處。 （2）淋巴管瘺患者M(jìn)RL圖像表現(xiàn)為造影劑外溢呈高信號，顯示成功率為22/23；18名淋巴瘺患者所在位置較表淺，另4名患者瘺位于深筋膜-肌間隙；淋巴管瘺SNR較腹股溝區(qū)淋巴結(jié)高，兩者有統(tǒng)計學(xué)差異（p＜0.05），淋巴管瘺信號強(qiáng)度SI上升速度較腹股溝區(qū)淋巴結(jié)慢，二者間有統(tǒng)計學(xué)差異（p＜0.05）；瘺持續(xù)時間≤8周的患者瘺冠狀面最大截面積、引流淋巴管數(shù)目以及最大徑均小于瘺持續(xù)時間＞8周的患者，以上比較均有統(tǒng)計差異（p＜0.05）。22名患者于磁共振檢查后完成手術(shù)治療，隨訪未見瘺復(fù)發(fā)。 結(jié)論：（1）磁共振淋巴造影MRL可以顯示婦科腫瘤術(shù)后繼發(fā)下肢淋巴水腫患者的外周淋巴系統(tǒng)的解剖學(xué)和形態(tài)學(xué)特征，為臨床診斷和水腫分期提供幫助，此外本研究還發(fā)現(xiàn)繼發(fā)性淋巴水腫患側(cè)小腿的形態(tài)學(xué)改變較大腿更明顯。 （2）磁共振淋巴造影MRL可以成為臨床診斷淋巴管瘺的可靠的影像學(xué)檢查方法，幫助臨床診斷、術(shù)前評估以及手術(shù)方案的制定；此外淋巴管瘺可能隨時間推移加重病情，保守治療無效時應(yīng)盡快手術(shù)治療。 第三部分新型淋巴特異性造影劑HA-Gd-DTPA復(fù)合物的研究 目的：通過適當(dāng)?shù)姆椒�，制備出新型淋巴特異性磁共振大分子陽性造影劑HA-Gd-DTPA復(fù)合物，通過磁共振淋巴造影顯像探索和評估其顯示正常淋巴系統(tǒng)以及良惡性淋巴結(jié)鑒別診斷方面的能力。 方法：（1）以透明質(zhì)酸納、二乙三胺五乙酸以及硝酸釓為主要原料通過化學(xué)橋接、螯合等制備出HA-Gd-DTPA復(fù)合物，并對該造影劑的理化性質(zhì)進(jìn)行檢測，通過MMT法考察其細(xì)胞毒性，用小鼠實驗考察其活體毒性并得到其半數(shù)致死量。 （2）以小分子造影劑馬根維顯作為對照，通過對正常新西蘭大白兔進(jìn)行磁共振淋巴造影，評估HA-Gd-DTPA復(fù)合物顯示正常淋巴系統(tǒng)的能力。 （3）用完全福氏佐劑和VX-2腫瘤瘤株分別制備淋巴結(jié)炎癥和腫瘤轉(zhuǎn)移模型，以馬根維顯為對照，考察HA-Gd-DTPA復(fù)合物鑒別良惡性淋巴結(jié)的能力。 結(jié)果：（1）新制備的HA-Gd-DPTA復(fù)合物結(jié)構(gòu)穩(wěn)定；水合粒徑平均為350納米，分子量為100000道爾頓；釓離子濃度為0.02±0.005mol/L；其弛豫性強(qiáng)于等濃度的馬根維顯，并且具有良好的生物安全性。 （2）正常動物磁共振淋巴造影成像顯示，HA-Gd-DTPA復(fù)合物組（A組）乆窩淋巴結(jié)信號強(qiáng)度達(dá)到峰值的時間（6.27±0.82）較馬根維顯組即B組（4.19±0.27）更長，兩者間有顯著性差異（p＜0.01）；A組乆窩淋巴結(jié)增強(qiáng)后到達(dá)峰值時，SNRmax=41.14±5.52，CNRmax=33.22±5.34，E%max=（375.55±55.72）%；B組乆窩淋巴結(jié)增強(qiáng)后到達(dá)峰值時，SNRmax=37.78±6.21，CNRmax=29.48±5.78，E%max=（345.50±42.80）%；A組乆窩淋巴結(jié)增強(qiáng)后信號下降斜率L=0.85±0.20，B組乆窩淋巴結(jié)增強(qiáng)后信號下降斜率L=1.02±0.15；A、B組間SNR、CNR、E%以及下降斜率比較均有統(tǒng)計學(xué)差異。 （3）在HA-Gd-DTPA磁共振增強(qiáng)造影圖像上，腫瘤轉(zhuǎn)移性淋巴結(jié)表現(xiàn)為斑片狀、斑點(diǎn)狀高信號，而炎性淋巴結(jié)呈均勻高信號且隨時間變化不大，二者強(qiáng)化形態(tài)存在明顯差異；腫瘤轉(zhuǎn)移性淋巴結(jié)強(qiáng)化到達(dá)峰值的時間較炎癥淋巴結(jié)長（p＜0.05），而且峰值信噪比SNR也低于炎癥淋巴結(jié)（p＜0.05）。對照病理，HA-Gd-DTPA復(fù)合物檢出炎性和腫瘤轉(zhuǎn)移性淋巴結(jié)多于馬根維顯，而且其敏感性和特異性更高。 結(jié)論：成功制備出新型親淋巴大分子磁共振陽性造影劑HA-Gd-DTPA復(fù)合物，該造影劑安全性好、分子結(jié)構(gòu)穩(wěn)定，弛豫性好，磁共振淋巴造影顯像表明其顯示正常淋巴系統(tǒng)優(yōu)于小分子磁共振造影劑馬根維顯，并可用于炎癥和腫瘤轉(zhuǎn)移性淋巴結(jié)的鑒別。
[Abstract]:The first part is the application of conventional magnetic resonance imaging in the diagnosis of lymphatic system related diseases.
Objective: (1) to evaluate the value of conventional magnetic resonance imaging (MRI) in the diagnosis of secondary lymphedema and to evaluate the value of its parameters in the early diagnosis and staging of lymphedema.
(2) to explore the accuracy of DWI and FDG-PET (CT) in evaluating and predicting the pathological response of rectal patients receiving NCRT treatment.
Methods: (1) 72 patients with secondary unilateral lower extremity lymphedema after gynecologic surgery and 22 patients with no apparent edema after gynecologic operation were scanned by T1WI, T2WI, T2 fat suppression sequence and magnetic resonance water imaging sequence, and the lower extremity lymphedema staging, the diameter of the leg (TT), the corresponding muscle diameter (MT), and subcutaneous soft group were analyzed. The correlation between thickness (STT), diameter difference between the affected side and the normal side (DTT), the difference of muscle diameter (DMT), and the difference of subcutaneous soft tissue thickness (DSTT).
(2) through the search and screening of database files, we finally entered into 33 documents and carried out meta-analysis. The evaluation indexes included sensitivity, specificity, PPV and NPV.
Results: (1) lymphedema was shown in conventional MRI images: the thickening of the dermis, the thickening of the subcutaneous tissue, the change of the meshes, the changes in the honeycomb shape, and the changes in the signal of the muscle tissue in the lymphedema. The.T2 fat suppression sequence could eliminate the interference of the fat signal, so the T2 fat suppression sequence was more beneficial to the display of lymphedema. Magnetic resonance hydrography can show cystic, bead like dilated lymphatics, subcutaneous fluid degree and scope, and subcutaneous meshes of the edema limb changes in the.T2 fat suppression sequence parameters, large affected side, TT, STT, DTT, SDTT of the calf, and lymphedema staging, but MT has no correlation, including the leg DSTT and thigh DTT and drenching. The correlation of the STT, DTT, DSTT and thigh DTT in the affected leg was statistically different (P value was less than 0.05), and the other parameters were not statistically different. According to the ROC curve, the difference of subcutaneous soft tissue thickness of the calf DSTT was the best parameter for evaluating the stage of lymphedema.
(2) the study found that the sensitivity of DWI and NPV were higher than that of PET or FDG PET-CT (P < 0.05), but the specificity and PPV of the two were not different (P > 0.05). The threshold effect was not found in this study. The regression analysis of the DW-MRI and FDG PET (CT) was the most important factor in the accuracy of diagnosis.
Conclusion: This study shows that conventional MRI can be used to assist the clinical diagnosis of lymphedema, and the difference of subcutaneous soft tissue thickness can be used as an indicator of early diagnosis and edema staging of patients with lymphedema, and helps to select the best time for treatment and treatment of.DWI in the evaluation of NCRT treatment for patients with rectal cancer. The pathological reaction is better than FDG PET (CT).
The second part is the value of magnetic resonance lymphography in the diagnosis of lymphedema related diseases.
Objective: To evaluate the diagnostic value of magnetic resonance lymphography (MRI) in the diagnosis of lymphedema secondary to lower extremity lymphedema after gynecological tumor operation.
Methods: (1) magnetic resonance lymphography was performed on 80 patients with secondary lower extremity lymphedema after gynecologic tumor surgery. The number of the affected side, the number of the calf lymphatics, the maximum diameter of the lymphatics were compared with the normal side, and the number and the maximum diameter of the lymphedema in the different stages of the lymphedema were statistically analyzed.
(2) 23 patients with inguinal lymphangitic fistula were examined by magnetic resonance imaging (MRI) to assess the success rate of Lymphangio fistula and the difference between lymph node imaging and lymph node imaging. At the same time, the patients were divided into 2 groups according to the duration of fistula. The maximum cross section of the coronary Lymphangio fistula, the number of drainage lymphatics and the difference between the maximum diameter were compared.
Results: (1) the number of calf lymphatics in secondary lymphedema after gynecologic tumor was more than that of normal side (P < 0.01), while there was no significant difference in the number of normal lateral lymphatic vessels in the affected side of the thigh (P > 0.05), and the number of calf lymphatics and the maximum diameter of the affected side were significantly different from that of the affected side (P < 0.01). There was no statistical difference between the 1 stage VS.2 stage and the 2 phase VS.3 stage, and there was no statistical difference between the 1 stage VS.3 stages and the maximum diameter of the lymphatic vessels in the affected side thighs (P > 0.05). There was no statistical difference between the 1 stages of the 1 stage of the lymphoid swelling of the affected leg. The difference, the 2 phase VS.3 and the 1 phase VS.3 period were statistically different (P values were all less than 0.05). The median number of lymphatic vessels in the affected side thighs was not statistically significant (P > 0.05). All the lower extremities were found to be 56 of the lymphatic reflux.
(2) the MRL image of the Lymphangio fistula patients showed that the contrast agent was high signal and the success rate was 22/23; the location of the 18 lympho fistula patients was shallow, and the other 4 patients were located in the deep fascia muscle space; the lymphatic fistula SNR was higher than the inguinal lymph node, and the two were statistically different (P < 0.05), and the signal intensity of lymphatic fistula was higher than that of SI. The lymph nodes in the inguinal region were slow, and there was a statistical difference between the two (P < 0.05); the maximum section area of the coronary artery in patients with fistula duration less than 8 weeks, the number of drainage lymphatics and the maximum diameter were less than the duration of the fistula duration > 8 weeks. The above comparison had statistical differences (P < 0.05).22 patients completed the surgical treatment after magnetic resonance examination, followed up. There was no recurrence of fistula.
Conclusions: (1) magnetic resonance lymphography MRL can show the anatomical and morphological features of the peripheral lymphatic system of the patients with secondary lower extremities after gynecologic tumor surgery, providing help for clinical diagnosis and edema staging. Furthermore, this study also found that the morphological changes of the side leg of secondary lymphedema are more obvious than those of the thighs.
(2) magnetic resonance lymphography MRL can be a reliable imaging method for clinical diagnosis of Lymphangio fistula. It helps clinical diagnosis, preoperative assessment and the formulation of surgical procedures; in addition, Lymphangio fistula may aggravate the condition with time, and the treatment should be done quickly when the conservative treatment is invalid.
The third part is the study of a novel lymphatic specific contrast agent HA-Gd-DTPA complex.
Objective: to prepare a new type of lymphoid magnetic resonance macromolecule positive contrast agent HA-Gd-DTPA complex by means of appropriate methods, and to explore and evaluate its ability to display the normal lymphatic system and the differential diagnosis of benign and malignant lymph nodes through magnetic resonance lymphography.
Methods: (1) the HA-Gd-DTPA complex was prepared by chemical bridging and chelating with hyaluronic acid, two B, three amine five acetic acid and gadolinium nitrate. The physicochemical properties of the contrast agent were detected, the cytotoxicity was examined by MMT, and the living toxicity was investigated in mice and half of the lethal dose was obtained.
(2) the ability of HA-Gd-DTPA complex to display normal lymphatic system was evaluated by magnetic resonance lymphography of normal New Zealand white rabbits by using a small molecular contrast agent, Ma root.
(3) the model of lymphadenitis and tumor metastasis was prepared by full Fu's adjuvant and VX-2 tumor tumor strain respectively. The ability of the HA-Gd-DTPA complex to identify the benign and malignant lymph nodes was investigated by the contrast of the HA-Gd-DTPA complex.
Results: (1) the structure of the newly prepared HA-Gd-DPTA complex is stable, the average diameter of the hydrated particles is 350 nanometers, the molecular weight is 100000 Dalton, the gadolinium ion concentration is 0.02 + 0.005mol/L, and the relaxation is stronger than the equal concentration of Ma gage, and it has good biological safety.
(2) the magnetic resonance lymphography of normal animals showed that the time of the signal intensity of the lymph node in the HA-Gd-DTPA complex group (A group) reached the peak value (6.27 + 0.82), which was longer than that in group B (4.19 + 0.27), which was significantly different (P < 0.01). When the lymph nodes in the A group reached the peak, SNRmax=41.14 + 5.52, CNRmax=33.22 + 5 .34, E%max= (375.55 + 55.72)%, SNRmax=37.78 + 6.21, CNRmax=29.48 5.78, E%max= (345.50 + 42.80)%, A in group A and L=0.85 + 0.20 after enhanced lymph node enhancement in A group, and L=1.02 + 0.15 in B group. There were statistical differences.
(3) on the HA-Gd-DTPA MRI enhanced imaging, the metastatic lymph nodes were flaky and high signal, while the inflammatory lymph nodes were homogeneous high signal and changed little with time, and the enhanced morphology of the two groups was significantly different, and the time of tumor metastatic lymph node to peak was longer than that of the inflammatory lymph nodes (P < 0.05). The peak signal to noise ratio (SNR) was also lower than that of the inflammatory lymph nodes (P < 0.05). The HA-Gd-DTPA complex detected inflammatory and metastatic lymph nodes more than that of Ma, and had higher sensitivity and specificity than that of the inflammatory lymph nodes (P < 0.05).
Conclusion: a new type of lymphoid macromolecule magnetic resonance positive contrast agent HA-Gd-DTPA complex is successfully prepared. The contrast agent has good safety, stable molecular structure and good relaxation. Magnetic resonance lymphography shows that the normal lymphatic lymphography shows that the normal lymphatic system is superior to the small molecular magnetic resonance contrast agent MA root, and can be used in inflammation and metastatic lymph nodes. The identification of the knot.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R445.2;R551.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 吳元魁;方挺松;陳大朝;劉國清;許乙凱;;Gd-DTPA和HSA-Gd-DTPA應(yīng)用于MR淋巴造影的對比研究[J];南方醫(yī)科大學(xué)學(xué)報;2007年10期

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3 彭孝蓮;吳宜林;孟杰;丁暉;;血管內(nèi)皮生長因子受體-3表達(dá)及D2-40標(biāo)記的微淋巴管密度與宮頸鱗癌淋巴轉(zhuǎn)移的關(guān)系[J];實用婦產(chǎn)科雜志;2010年12期

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