Gd-DTPA Based Interstitial Magnetic Resonance Lymphography

Objectives:Breast cancer is a serious health hazard for women of all the world. Lymph nodemetastasis is the main transfer method of breast cancer and accurate diagnosis of them isimportant for tumor staging, surgery planning, and prognosis determining. Sentinel lymphynode (SLN) is the first lymph node draining the tumor and, if negative, to predict the statusof the remaining distant nodes. SLNB are the standard procedure to detect axillary lymphnodes metastasis. To identify SLN, g-probe-guided method has the problem of radioactivetracer using and technical difficulties for external r-probe counting. On the other hand, thismethod must be performed in a hospital that can handle radioactive materials. Dye-guidedmethod is intraoperative and lack of accurate anatomical landmarks and geometry. Theanatomical relation between tumor, lymph-vessels, and SLN could not be recognized.Hence, there is urgent need for a safe and simple technique to detect SLN.Gadolinium based interstitial magnetic resonance lymphography (Gd-IMRL) is amethod that can display lymphatic vessels and lymph nodes in MRI after interstitialinjection of Gadolinium contrast agent. This technology has been proven to be a goodmethod in the lower extremities and neck lymph system imaging. We hypothesis that thistechnology would also be able to image axillary lymph system and help identify the SLN ofbreast cancer.In this study we first establish the Gd-IMRL technology of axillary system imaging inbreast cancer, and then investigate its clinical value in SLN identification and metastasisdetection.The main purpose including:1. To investigate the feasibility of axillary lymph system imaging usingGadolinium-diethylene triamine pentaacetic acids (Gd-DTPA) based interstitial magneticresonance lymphography (IMRL) in patients with breast cancer. 2. To evaluate the value of Gd-DTPA based IMRL to identify and diagnose sentinellymph node metastasis of breast cancer.3. To investigate the feasibility of internal mammary lymph system imaging usingGd-DTPA based IMRL in patients with breast cancer.Methods:1. From January2012to June201224patients with breast cancer were consecutivecollected and divided into three groups.15ml Gd-DTPA and2ml2%lidocaine were mixedand0.3ml,0.5ml,1.0ml of them were subcutaneously injected into the outside of themammary areola for the three groups separately. MRI were performed with Siemens3.0TMagnetom Trio MRI instrument using volumetric interpolated breath-hold examination(VIBE) sequence. The enhanced number, enhanced degree and enhanced time in axillaryregions I-III of different group were analyzed and compared.2. From April2012to January2014,58patients with breast cancer were consecutivecollected.15ml of Gd-DTPA and2ml of mepivacain hydrochloride2%were mixed and0.5ml of them was injected into the outside of the subareolar breast tissue. MRI wereperformed with Siemens3.0T Magnetom Trio MRI instrument using volumetricinterpolated breath-hold examination (VIBE) sequence. Axillary lymph flow was trackedand sentinel lymph nodes were identified by Gd-IMRL as M-SLN. All M-SLN were markedby a method of surface capsule localization. During surgery, methylene blue was used astracer and SLNs stained by it were detected and excised by following the blue lymphaticvessels. These were designated as D-SLN. The numbers of SLNs detected by Gd-MRL andstained by methylene blue during operation were compared by paired test. After pathology,using the diagnostic criteria for pelvic lymph nodes reported in the literature, the accuracyof SLN metastasis detection of Gd-MRL imaging were examined.3. From March2013to June2014,12patients with breast cancer were consecutivecollected.15ml of Gd-DTPA and2ml of mepivacain hydrochloride2%were mixed and1ml of them was injected into the inside of the subareolar breast tissue. MRI wereperformed with Siemens3.0T Magnetom Trio MRI instrument using volumetricinterpolated breath-hold examination (VIBE) sequence. The number of enhanced internalmammary lymph nodes and their enhancing time were observed and analyzed.Results:1. All of the24patients completed their examinations successfully without anyunexpected adverse events. The enhanced lymph node number of axillary I-III regions showed significant difference among three groups（F=7.8, F=15.51, F=17.34, P<0.001). Inpairwise comparison1ml group=0.5ml group>0.3ml group were found for axillary I-IIregions and1ml group>0.5ml group>0.3ml group were found for axillary III regions(Post Hoc (SNK) test, P<0.001). The maximum enhancing time were14.9±3.3min,14.8±3.5min and14.9±3.1min for the0.3ml,0.5ml and1ml group respectively, whichshowed no significant difference. The biggest enhancement value of each group were187±11.3，205±10.8and223±13.2for the0.3ml,0.5ml and1ml group respectively, whichshowed significant differences (F=26.41, P<0.001). In pairwise comparison,1ml group﹥0.5ml group﹥0.3group were found (Post Hoc (SNK) test, P<0.001).2. A total of75M-SLNs (average1.60±0.52) were identified by MRL (Magneticresonance lymphography). The enhancing time was12.3±3.5min, range from10min to16min. During operation, all M-SLNs were easily resected under the guidance of skinmarker and3D MR imaging. The distance between the skin markers and the SLNs were1.18±0.56cm. Totally91D-SLNs (average1.94±0.63) were stained by methylene blue,which was significant more than those of the M-SLNs. There is a strong correlation(Spearman’s rank correlation coefficient0.69, P <0.001) between the SLNs identified bythis two methods. After obtaining pathological findings, interstitial magnetic resonancelymphography gave a sensitivity of96.8%, a specificity of95.5%and an accuracy96.0%for benign and malignant axillary lymph SLNs discrimination.3. All of the12patients completed their examinations successfully without anyunexpected adverse events. Totally10internal mammary lymph nodes were enhanced. Theenhancing time was13.2min, range from14.2min to9.2min. In one case one axillary andone mammary sentinel lymph nodes were enhanced together.Conclusions:1. Gd-DTPA based IMRL can imaging axillary lymph system effectively in patientswith breast cancer.2. Gd-DTPA based IMRL can accurately identify the axillary sentinel lymph node andguide the biopsy. It may has great clinical value in the future.3. Gd-DTPA based IMRL can imaging internal mammary lymph system effectively inpatients with breast cancer.