The Application Of Magnetic Resonance Imaging In Diseases Of The Lymphatic System And The Research Of A New Lymphatic Specificity Contrast Agent

PART1Conventional magnetic resonance imaging (MRI) in theapplication of lymphedema diagnosis and stagingPurpose:（1）To explore the value of conventional MRI in the application oflymphedema diagnosis and staging.（2）The aim is to evaluate the diagnostic accuracy of DW-MRI relative toFDG PET (CT) in the evaluation and prediction of pathological response in patientswith rectal cancer receiving NCRT.Methods:（1）Seventy-two females with unilateral lower extremity lymphedema(LEL) and twenty-two participants without LEL underwent lower extremities MRIafter treatment of uterine malignancies. The sequences included T1WI, T2WI, T2fat-suppression and magnetic resonance hydrography. On fat-suppressed T2-weightedmid-axial images of calves and thighs, total thickness of soft tissue (TT), musclethickness (MT) and subcutaneous tissue thickness (STT) as well as the differencesinTT, MT and STT from the contralateral lower extremity (expressed as DTT, DMTand DSTT respectively) were obtained, and analyzed statistically for staging LEL.（2）Through the database file retrieval and filtering,33literatures wereenrolled and meta–analysis was made. The evaluation index included sensitivity,specificity, PPV and NPV.Results:(1) The findings of Lymphedema in conventional MRI included dermalthickening, thickening of subcutaneous tissue, grid change, and honeycombing.Lymphedema did not cause signal change of muscle tissue. T2fat suppressionsequence can eliminate fat signal interference, so it is conducive to observationlymphedema. MR hydrography can show the saccate and beaded lymphatic vessel,the degree and range of subcutaneous hydrops, and subcutaneous grid. An increasing trend was found in TT and STT of the affected calf and thigh with increasing stages ofLEL on fat-suppressed T2-weighted images. Both parameters were strongly andmoderately correlated with LEL stages, respectively. Both DTT and DSTT of calvesor thighs were strongly correlated with LEL stages (all p <0.05). Among parameters,DSTT of calves could best stage LEL with an area under receiver operating curve ofmore than0.89.（2）In this meta-analysis, we found DW-MRI had higher pooled sensitivityand NPV estimates than those for FDG PET (CT)(p＜0.05). No differences wereseen between the pooled specificity, PPV estimate for DW-MRI and those for FDGPET (CT)(p>0.05). No threshold effect was found. The results of meta-regressionanalysis indicate that whether the evaluation of DW-MRI, FDG PET (CT) results wasperformed blinded to the reference standard is the most important (significant)characteristic influencing diagnostic accuracy.Conclusions: The study shows that conventional MRI can be used for clinicaldiagnosis of secondary lymphedema. The difference of subcutaneous tissue thicknesscan be used as index of diagnosis and staging for early lymphedema, and help clinicaldocter choose the best treatment time and treatment plan. DW-MRI has goodperformance in the evaluation and prediction of pathological response to neoadjuvanttherapy in rectal cancer patients and is superior to FDG PET (CT). PART2The value of Magnetic resonance lymphography in thelymphedema related diseasesPurpose: To explore the feasibility of using3.0T high-resolution MR lymphographyto characterize inguinal lymphatic vessel leakage (LVL) and lymphatic vesselmorphology in lower extremity lymphedema secondary to gynecologic carcinomatreatment.Methods:(1) Eighty females with lower extremity lymphedema secondary togynecologic carcinoma treatment underwent MR lymphography (MRL) at3T. Lymphatic vessel morphology in normal and affected limbs was compared.(2) Twenty-three patients with known inguinal LVL underwent MRlymphangiography and T2-weighted imaging. The presence or absence of inguinalLVL and the responsible lymphatic vessels were determined using the above imagingmodalities and confirmed by surgical procedure. Divide patients into two groupsaccording to duration time of fistula, and then to comparative analysis of fistula area,the number of lymphatic drainage and the largest size of lymphatic drainage betweenthe two groups.Results:(1) The median number of lymphatic vessels visualized in normal calf wasless than that in the lymphedematous calf (p＜0.01), while no significant differencewas found between the normal thigh and swollen thigh. The median diameter of thelymphatic vessels in swollen calf and thigh were significantly larger than that in thecontralateral calf and thigh, respectively (p＜0.05). Lymphatic vessel number in theaffected calf was significantly greater than that in affected thigh and the meandiameter of affected calf was also significantly wider than that of affected thigh (p＜0.01). Mean diameter of lymphatic vessels in the affected calf was significantlydifferent between stage I and stage III (p＜0.05), but not significantly differentbetween stages I and II, and between stages II and III (p＞0.05). The median numberof lymphatic vessels for affected calf showed significant difference between stage Iand stage III, and between stage II and stage III (p＜0.05), but no significantdifference between stage I and stage II (p＜0.05). There was no significant differencein mean diameter or median number of lymphatic vessels in the affected thigh foundbetween different stages (p＞0.05). Dermal back flow was identified in56(63.6%) ofthe88affected extremities.(2) Specific inguinal LVL enhancement patterns and leaking lymphaticvessels were detected in22of23patients. Compared to the SNR of enhanced lymphnodes, that of the enhanced LVL was significantly greater (p <0.01), thereby makingit possible to differentiate between LVL sites and enhancing inguinal lymph nodes.Furthermore, the steepest contrast enhancement curve slope of enhanced LVL was lower than that of enhanced lymph nodes (p＜0.05). Fistula duration of eight weeksor less had a less coronal maximum area, numbers and diameter of lymphatic drainagethan patients with fistula duration more than8weeks (all p＜0.05). After MRdiagnosis,22patients successfully underwent open exploration and ligation of theleaking lymphatic vessel. Clinical follow-up did not demonstrate recurrence oflymphatic fluid in the groin.Conclusions:(1) MR lymphography can be helpful in diagnosis or clinical staging forlower extremity with gynecologic oncology-related lymphedema, and the studyshowed that morphological changes of crus with secondary lymphedema is moreobvious than thigh relatively.(2) High-resolution MR lymphangiography is a promising approach toidentifying specific features of lymphatic vessel leakage in the groin, moreoverlymphatic vessel leakage may aggravate over time, when conservative treatment isinvalid surgical treatment as soon as possible. PART3Research of a new Lymphatic Specificity Contrast Agent：HA-Gd-DTPAPurpose: To develop a new type of macromolecular positive lymph specificity of mricontrast agent HA-Gd-DTPA complexes in an appropriate method for targetinglymphatic system, exploring and the evaluating of the the contrast agents in benignand malignant lymph nodes diagnosis.Methods:(1) With hyaluronic acid, DTPA and gadolinium nitrate as the main rawmaterial was prepared by chemical bridging and chelating to develop HA-Gd-DTPAcomplexes, and test its physical and chemical properties. To investigate thecytotoxicity by the MMT method; Using mice to investigate the toxicity of living andto get the half lethal dose.(2) With Magnevist as control, to evaluate the HA-Gd-DTPA compounds showed normal lymphatic system by MR lymphangiography on rabbit.(3) Preparation of lymph node inflammation and tumor metastasis modelwith complete adjuvant and VX-2cancer tumor strains, respectively. Investigate itsability to differentiate benign and malignant lymph nodes on MR lymphangiography.Results:(1) The HA-Gd-DPTA complex structure is stable, safe, its hydrate particlesize of an average of350nm, its molecular weight is100000Dalton, and itsGadolinium concentration is0.02±0.005mol/L, with a higher relaxation thanmagnevist.(2) Findings of MR lymphangiography on normal rabbit：Popliteal fossalymph node signal intensity reach the peak of HA-Gd-DPTA complex group (Group A)is slower than magnevist group (Group B)(p＜0.05). In Group A, SNRmax=41.14±5.52, CNRmax=33.22±5.34, E%max=（375.55±55.72）%, L=0.85±0.20; InGroup B, SNRmax=37.78±6.21, CNRmax=29.48±5.78, E%max=（345.50±42.80）%, L=1.02±0.15, respectively. These comparisons are statistically significant(p＜0.05).(3) The metastatic tumor lymph nodes showed patchy or punctate high signalin MR lymphangiography with HA-Gd-DPTA complex, but the inflammatory lymphnode displayed homogeneously high signal and little change over time. The tumormetastatic lymph nodes’ peak time was longer than inflammatory lymph nodes (p＜0.05), and its’ peak SNR was also lower than inflammatory lymph nodes (p＜0.05).For differentiation benign and malignant lymph nodes on MR lymphangiography,HA-Gd-DPTA complex had a higher sensitivity and specificity than magnevist.Conclusions: HA-Gd-DPTA complex as a new type of macromolecular MR contrastagent`is safe, stable, and have good relaxation. MR lymphangiography imagingshowed that its display normal lymphatic system is better than magnevist, which is asmall molecular MR contrast agents, and can be used in differential diagnosis ofbenign and malignant lymph nodes.