Experimental Study On The Differential Diagnosis Of Metastatic And Inflammatory Hyperplasia Lymphnodes With The Use Of SPIO-Enhanced MRI

PartⅠAnimal Model Experiment On Optimal Injection Approach To Manifest The Rabbits'Popliteal Lymph Node with The Use Of SPIO-enhanced MRI:A Initial StudyObjectiveTo investigate the optimal injection approach to show the rabbits'popliteal lymph node with enhanced MRI using SPIO.Materials And MethodsEquipments and reagents:①GE SIGNA EXCITE 1.5T MRI scanner.②Rabbit scan dedicated coils.③Eggs,normal saline.④sodium pentobarbital(3%).⑤Superparamagnetic iron oxide particles (SPIO).⑥12 New Zealand white rabbits:male or female,2～2.5kg. Experiment steps:(1) To establish model of popliteal lymph node with reactive hyperplasia: 12 rabbits underwent intramuscular injection of liquid egg yolk (1:1) in hind leg muscle; after a repeated injection 3 days later, and the model was successfully created 7-8 days later. (2) 12 white rabbits were divided into two groups randomly. (3)MR protocol:T1WI, T2WI, GRE T2* WI. Pre-enhanced scan was obtained before the injection of SPIO. After that,20μmolFe per limb was injected through the ear vein for group 1;10μmolFe per limb were injected by the hind toe web for group 2. MRI scan was repeated 12 hours after the injection. (4) After all scans were finished, lymph nodes were sent for pathological examination which included HE staining and Prussian blue staining.(5)Analyzing MRI and pathological images. Data were statistically analyzed. Measuring the size the signal intensity of the lymph nodes in all series in two groups and calculating the signal to noise ratio (SNR).ResultsThe size of lymph node in two groups (x±s) were (9.81±0.62) and (9.84±0.70) mm, respectively. There was no statistical difference with T-test in the two groups (p= 0.936,> 0.05) of lymph nodes in the size. In unenhanced scan, the two groups of lymphnodes showed the same signal intensity. Compared with the muscle, in T1WI sequence lymphnodes showed slightly lower signal intensity; in T2WI sequence lymphnodes showed equal signal intensity or high signal intensity; in GRE T2*WI sequence lymphnodes showed equal signal or higher signal intensity. After administration of SPIO, there were no signal intensity changes in any sequence. In group 2, most of lymph nodes showed low signal intensity in all sequences, even in the GRE T2*WI overdosing artifact appeared. Before and after administrated SPIO, in group 1, the SNR of the T1WI image were 85.51±15.13; 82.00±12.74 respectively, the SNR of the T2WI were151.01±22.34 and 147.19±20.14 respectively, the SNR of the GRE T2* WI were149.77±24.67 and 155.09±19.97 respectively. In group 2, the SNR of the T1WI were 92.48±4.98 and 24.68±2.2 respectively; the SNR of the T2WI were 154.48±16.21and 26.59±3.69 respectively; the SNR of the GRE T2*WI were 152.22±10.74 and 3.75±0.68 respectively. Repeated measures analysis of variance was P<0.01.ConclusionThe optimal approach of administrating SPIO to show rabbits popliteal lymphnodes is the intradermal injection in toe web.Part II SPIO And Gd-DTPA Enhanced MRI For The Diagnosis Of Metastatic And Inflammatory Hyperplasia Lymphnodes Lesions:A Experimental StudyObjectiveTo compare the ability of differential diagnosis with SPIO and Gd-DTPA respectively in lymph nodes in benign and malignant diseases using in MRI enhanced examinationMaterials and methodsEquipments and reagents:①GE SIGNA EXCITE 1.5T MRI scanner.②Rabbit scan dedicated coils.③Eggs, normal saline.④sodium pentobarbital (3%).⑤Superparamagnetic iron oxide particles (SPIO).⑥12 New Zealand white rabbits:male or female,2～2.5kg. Experiment steps:(1)To Establish animal models:①3-4 weeks after administration of VX2 tumor cell in the hind leg muscles of rabbits, metastasis of popliteal lymph node could be detected. A total of 12 rabbits were enrolled in this group.②A popliteal lymph node reactive hyperplasia model was established one week after administration of the liquid egg yolk in the rabbit hind leg muscle twice. A total of 12 rabbits were enrolled in this group. (2)Gd-DTPA and SPIO enhanced MRI scan were performed in all rabbits respectively. (3)pre-enhanced MRI scan Sequences:T1WI, T2WI, PDWI, GRE T2*WI. After pre-enhanced scanning, enhanced MR scan using Gd-DTPA of T1WI was applied.2 days later,we injected SPIO through the lower limb toe web.12 hours after that, enhanced MRI scan was applied. MRI sequences included T1WI, T2WI, PDWI, GRE T2* WI. (3)After scanning, lymph nodes specimens were sent for pathological examination, including HE staining and Prussian blue staining. (4)Diagnosis with two experts of MRI imaging(over 10 years of experience) was performed ignorant of pathological results. (5)Statistical analysis and image analysis were performed. Diagnostic results were compared with pathologic diagnosis, for Kappa test and ROC curve analysisResultsThe size of lymph node in two groups (x±s) were (9.50±0.57) and (9.65±0.59) mm, respectively. There was no statistical difference with T-test in the two groups (p= 0.651,> 0.05) of lymph nodes in the size. The signal intensities of lymph nodes in the two groups were similar in pre-enhanced MR scan. Compared with muscle signal intensity, in T1WI sequence lymphnodes showed slightly lower signal intensity; in T2WI sequences lymphnodes showed higher signal intensity; in PDWI sequence lymph nodes showed slightly higher signal intensity; in GRE T2*WI sequences lymph nodes showed higher signal intensity. Using Gd-DTPA contrast agent, lymph nodes in two groups appeared homogeneous or heterogeneous enhancement; Using SPIO contrast agent, there was no significant signal change in lymph nodes of the most tumor group. Reactive hyperplasia lymphnodes in T1WI, T2WI, PDWI and GRE T2* WI sequence showed low signal intensity, artifacts could be seen in the GRE T2*WI sequence. The two experts diagnosed imaging ignorant of pathologic findings. Using SPIO contrast agent.the sensitivity and specificity were both 83.3%; Using Gd-DTPA contrast agent, the sensitivity and specificity were 58.3% and 66.7% respectively. Youden index (YI) were 67% and 25%, respectively. Using SPIO contrast agent positive predictive value and negative predictive value were both 83.3%; Using Gd-DTPA contrast agent,the positive predictive value and negative predictive value were 63.6% and 61.5% respectively. For comparison of SPIO enhanced MRI and pathological examination, Kappa= 0.667, P= 0.01<0.05. For comparison of Gd-DTPA enhanced MRI and pathological examination, Kappa= 0.25, P= 0.219> 0.05. For comparison of SPIO enhanced MRI with Gd-DTPA enhanced MRI, Kappa= 0.250, P = 0.219> 0.05. Areas under the curve of ROC of the two methods were 0.833,0.625, and P values were 0.006 and 0.299 respectively.ConclusionSPIO is a new MRI contrast agent and has been proved high specificity and sensitivity in discriminating lymph nodes in benign and malignant lesions.