MRI With SPIO-carbon Dye Mixture For Detection Of Metastatic Lymph Nodes In VX2 Tumor Rabbits: Experimental Study

This study was divided into two parts: Part One, to evaluate the feasibility of interstitial MR lymphography (MRL) with SPIO-carbon dye mixture (SPIO-C) as a contrast agent in rabbits, and to explore the optimized examination time after administration; Part Two, to assess the value of the differential diagnosis and biopsy guidance for malignant and benign lymph nodes with SPIO-C as a contrast agent of MRL.Part One: The feasibility study of SPIO-C as an interstitial contrast agent of MRL in rabbits0bjective To evaluate the feasibility of SPIO-C-enhanced interstitial MRL in rabbits, as well as the optimized examination time after administration.Materials and methods 12 healthy adult New Zealand rabbits were randomly divided into two groups (Group 1, the contrast agent was SPIO; Group 2, SPIO-C was used; both dilute strength were 10μmol Fe/mL). TlWI, T2WI and T2*WI of bilateral popliteal areas were obtained before and enhanced scan were performed at 3, 6, 9, 12 and 24 hours, respectively, after interstitial administration of SPIO or SPIO-C (dose, 1 mL). The signal intensity and axial size of all lymph nodes were measured on different sequences before and after contrast enhancement.The signal to noise ratio (SNR) and Enhancing rate (E%) were also calculated and compared, then the signal intensity-time curve was drew. The differences in SNR between the two groups of nodes were evaluated for statistical significance with a completely random design t-test by using a P value at the 0.05 significance level.Results 15 popliteal lymph nodes were observed on MRI in Group 1, and 14 nodes in Group 2, respectively. The lymph nodes SNR of two groups in the three MRI sequences and different scan time had no significant difference (P>0.05). The lymph nodes T2WI-E% reduced by 60.03%, 69.10%, 70.36%, 60.36% on 3h, 9h, 12h and 24h respectively. There were pronounced overdose effects in 2 lymph nodes on 9h, but 9 nodes on 12h. Only on 9h, the difference of the lymph nodes'axial diameters in between all the three MRI sequence and postmortem measurements did not prove statistically significant(P>0.05, Dunnett test). Conclusion (1) The signal changes in normal lymph nodes caused by SPIO and SPIO-C is consistent. (2) SPIO-C as contrast agent on interstitial MRL, the optimized examination time after administration is at 9h.Part Two:Detection and differentiation of malignant from benign lymph nodes with SPIO-C-enhanced interstitial MRL0bjective To assess the value of the differential diagnosis and biopsy guidance for malignant and benign lymph nodes with SPIO-C as a contrast agent of MRL.Materials and Methods 36 healthy adult New Zealand rabbits were randomly divided into three groups. Reactively hyperplastic lymph node model was established in 12 animals by intramuscular injection of 0.5 ml egg yolk emulsion into the bilateral hindleg, and tumor-bearing lymph node model was established by intramuscular injection of 0.5 ml VX2 tumor tissue mass suspension in another 12 rabbits, and the other 12 rabbits were chosen as normal control group. Tl, T2 and T2*-weighted MR images of bilateral popliteal areas were obtained before and 9 hours after subcutaneous injection of SPIO-carbon dye mixture (SPIO-C, dose, 10μmol Fe/extrimity) into the dorsal footpads of all rabbits. The signal intensity and axial size of all lymph nodes were measured on different sequences of images before and after contrast enhancement, and SNR and E% of enhancing lymph nodes were calculated. Axial size, enhancement patterns, 6-point scale, and E% were compared among normal, inflammatory, and metastatic nodes according to the pathology. Results were evaluated by using receiver operating characteristic (ROC) analysis.Results 79 popliteal lymph nodes were observed on MRI, divided into three groups: normal lymph nodes (n=35), reactive lymph nodes (n=25), and metastatic lymph nodes (n=19), according to the pathology. The lymph nodes SNR of the three groups on MRI before contrast had no significant difference (P>0.05). The efficacy of T2WI-E% for diagnosis of metastatic lymph nodes showed a significantly bigger area under the ROC curve (Az=0.956±0.025, 95% confidence interval: 0.907-1.000) than those of axial diameter (Az=0.776±0.051, 95% confidence interval: 0.677-0.875), enhancement patterns (Az=0.883±0.052, 95% confidence interval: 0.781-0.986), and 6-point scale (Az=0.814±0.064, 95% confidence interval: 0.688-0.939). According to T2WI-E%, all the 79 lymph nodes then divided into two new groups: certain diagnosis group(including metastatic (n=14) and benign (n=48) lymph nodes), uncertain diagnosis group(n=17). Black carbon dye depositing in the lymph nodes'surface were observed in all postmortem lymph nodes.Conclusion (1) Enhancement performance and signal intensity quantitative measurement before and after SPIO-C enhanced interstitial MRL were effectively able to distinguish benign lymph nodes from malignant ones; (2) The efficacy of T2WI-E% for diagnosis of metastatic lymph nodes showed significantly greater than that of others, and according to T2WI-E%, lymph nodes could divide into certain diagnosis group (biopsy non-required) and uncertain diagnosis group (biopsy required). (3) Lymph nodes in uncertain diagnosis group could be biopsed under the guidance of MRI and carbon dye marker.