Assessment Of Radiofrequency Ablation Margin By MRI-MRI .

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World J Gastroenterol 2015 May 7; 21(17): 5345-5351ISSN 1007-9327 (print) ISSN 2219-2840 (online)Submit a Manuscript: http://www.wjgnet.com/esps/Help Desk: http://www.wjgnet.com/esps/helpdesk.aspxDOI: 10.3748/wjg.v21.i17.5345 2015 Baishideng Publishing Group Inc. All rights reserved.ORIGINAL ARTICLEProspective StudyAssessment of radiofrequency ablation margin by MRI-MRIimage fusion in hepatocellular carcinomaXiao-Li Wang, Kai Li, Zhong-Zhen Su, Ze-Ping Huang, Ping Wang, Rong-Qin ZhengAbstractXiao-Li Wang, Kai Li, Zhong-Zhen Su, Ze-Ping Huang,Ping Wang, Rong-Qin Zheng, Department of Ultrasound, theThird Affiliated Hospital of Sun Yat-sen University, Guangzhou510630, Guangdong Province, ChinaAuthor contributions: Wang XL and Li K contributed equallyto this work; Wang XL, Li K, Su ZZ, Huang ZP, Wang P andZheng RQ designed the study; Wang XL, Li K, Su ZZ, Huang ZPand Wang P performed the research and analyzed the data; WangXL and Li K wrote the paper; and Zheng RQ supervised thestudy.Supported by National Natural Science Foundation of China,No. 81271669, No. 81430038 and No. 81301931.Ethics approval: The study was reviewed and approved by theThird Affiliated Hospital of Sun Yat-sen University InstitutionalReview Board.Informed consent: All study participants, or their legal guardian,provided informed written consent prior to study enrollment.Conflict-of-interest: No conflict of interest.Data sharing: No additional data are available.Open-Access: This article is an open-access article which wasselected by an in-house editor and fully peer-reviewed by externalreviewers. It is distributed in accordance with the CreativeCommons Attribution Non Commercial (CC BY-NC 4.0) license,which permits others to distribute, remix, adapt, build upon thiswork non-commercially, and license their derivative works ondifferent terms, provided the original work is properly cited andthe use is non-commercial. See: espondence to: Rong-Qin Zheng, PhD, Departmentof Ultrasound, the Third Affiliated Hospital of Sun Yatsen University, No. 600 Tianhe Road, Guangzhou 510630,Guangdong Province, China. mysonoworld@163.comTelephone: 86-20-85252416Fax: 86-20-85252416Received: October 26, 2014Peer-review started: October 29, 2014First decision: November 14, 2014Revised: December 6, 2014Accepted: February 11, 2015Article in press: February 11, 2015Published online: May 7, 2015WJG www.wjgnet.comAIM: To investigate the feasibility and clinical value ofmagnetic resonance imaging (MRI)-MRI image fusionin assessing the ablative margin (AM) for hepatocellularcarcinoma (HCC).METHODS: A newly developed ultrasound workstationfor MRI-MRI image fusion was used to evaluate the AMof 62 tumors in 52 HCC patients after radiofrequencyablation (RFA). The lesions were divided into twogroups: group A, in which the tumor was completelyablated and 5 mm AM was achieved (n 32); andgroup B, in which the tumor was completely ablated but5 mm AM was not achieved (n 29). To detect localtumor progression (LTP), all patients were followedevery two months by contrast-enhanced ultrasound,contrast-enhanced MRI or computed tomography (CT)in the first year after RFA. Then, the follow-up intervalwas prolonged to every three months after the firstyear.RESULTS: Of the 62 tumors, MRI-MRI image fusionwas successful in 61 (98.4%); the remaining case hadsignificant deformation of the liver and massive ascitesafter RFA. The time required for creating image fusionand AM evaluation was 15.5 5.5 min (range: 8-22min) and 9.6 3.2 min (range: 6-14 min), respectively.The follow-up period ranged from 1-23 mo (14.2 5.4 mo). In group A, no LTP was detected in 32lesions, whereas in group B, LTP was detected in 4 of29 tumors, which occurred at 2, 7, 9, and 15 mo afterRFA. The frequency of LTP in group B (13.8%; 4/29)was significantly higher than that in group A (0/32, P 0.046). All of the LTPs occurred in the area in which the5 mm AM was not achieved.CONCLUSION: The MRI-MRI image fusion using5345May 7, 2015 Volume 21 Issue 17

Wang XL et al . Ablative margin assessed by image fusionan ultrasound workstation is feasible and useful forevaluating the AM after RFA for HCC.index tumor from the surrounding hepatic parenchymain the ablative area. In addition, the original position ofthe index tumor in the ablative area cannot be clearlydetermined after RFA. Thus, accurately determiningwhether the ablative area overlaps with the entire AMrange using routine imaging methods is difficult.The recent development of new image fusiontechniques has made it possible to accurately assess[21,22]the AM and therapeutic responses to RFA for HCC.[21]Kim et alquantitatively assessed the ablative areaand margins using 3D CT image fusion before andafter RFA for HCC. Their study demonstrated that theminimal AM should be 3 mm for preventing LTP.[22]Fujioka et alevaluated the therapeutic response toRFA for HCC using image registration of preoperativeand postoperative CT. They found that this imagingtechnique can facilitate illustrating the relationshipbetween tumor and ablation zone. More recently,[23]Su et alassessed the HCC AM after ablation using3DCEUS-CT/MRI image fusion with encouraging resultsthat also indicated the promising value of imagefusion in determining the AM. Compared with CT andCEUS, MRI is more sensitive and frequently used inthe evaluation of liver lesions and tumor treatmentresponse. To the best of our knowledge, the use ofMRI-MRI image fusion for evaluating the AM after RFAhas not been reported.This study aimed to explore the feasibility andclinical value of a newly developed MRI-MRI imagefusion method in assessing AM after RFA for HCC.Key words: Hepatocellular carcinoma; Radiofrequencyablation; Image fusion; Magnetic resonance image;Ablative margin The Author(s) 2015. Published by Baishideng PublishingGroup Inc. All rights reserved.Core tip: One of the major factors that impact thetherapeutic effectiveness of radiofrequency ablation(RFA) for hepatocellular carcinoma (HCC) is local tumorprogression (LTP), which is primarily attributed toinsufficient ablative margins (AMs). Traditional imageevaluation methods, including contrast-enhancedultrasound and side-by-side comparison with computedtomography/magnetic resonance imaging (MRI)images, cannot quantitatively determine the AM inthree dimensions. Our study was the first to report thefeasibility of MRI-MRI image fusion using a commercialultrasound workstation to assess the RFA AM for HCC.The results demonstrated that this method specificallydescribes the direction of the insufficient ablative zoneand would be helpful for the early detection of LTP.Wang XL, Li K, Su ZZ, Huang ZP, Wang P, Zheng RQ.Assessment of radiofrequency ablation margin by MRI-MRIimage fusion in hepatocellular carcinoma. World J Gastroenterol2015; 21(17): 5345-5351 Available from: URL: htm DOI: S AND METHODSPatients and tumorsThe study was approved by the Institutional ReviewBoard, and written informed consent was obtainedfrom all patients. Between October 2009 andSeptember 2011, 52 patients (46 men and 6 women,aged 50.2 17.5 years, range: 27-74 years) with62 HCC tumors who underwent RFA with confirmedcomplete ablation by MRI in the first month after RFAwere enrolled into this study. All of the 62 liver lesions[24]were pathologically or clinically diagnosed as HCC .The baseline characteristics of the patients are shownin Table 1.INTRODUCTIONHepatocellular carcinoma (HCC) is the fifth mostcommon cancer and the third most common cause ofcancer deaths in the world. Radiofrequency ablation(RFA) has been widely performed as a minimallyinvasive treatment modality for HCC with a highsuccess rate of complete tumor ablation. However,recent studies reported high incidences (1.7%-41%)[1-10]of local tumor progression (LTP) after RFA for HCC.The main risk factors for LTP include large tumorsize, insufficient ablative margins (AMs) and poor[11-17]histological grade. In previous studies, the AMwas assessed by comparing the axial images ofcomputed tomography (CT)-magnetic resonanceimaging (MRI) or contrast-enhanced ultrasound(CEUS) obtained before and after RFA using a side-by[18-20]side approach. These approaches are somewhatsubjective and have limited ability to accuratelyassess the AM. Commonly, the index tumor and itssurrounding hepatic parenchyma are mixed afterablation and appear on routine CT/MRI or CEUS, anarea that lacks contrast enhancement. No conventionalimaging methods can be used to differentiate theWJG www.wjgnet.comRFA procedureAll RFA procedures were performed by using a CoolTip radiofrequency system (Radionics Inc, Burlington,MA) under ultrasound guidance (My Lab Twice,Esoate, Genoa, Italy). A total of 59 lesions in 49patients underwent percutaneous RFA, whereas 3cases underwent laparotomy RFA. RFA combinedwith percutaneous ethanol injection treatment (PEIT)was performed in 3 cases, and transcatheter hepaticarterial chemoembolization (TACE) 3 wk beforeRFA was performed in 6 cases. All procedures wereperformed by 2 experienced ultrasound physicians5346May 7, 2015 Volume 21 Issue 17

Wang XL et al . Ablative margin assessed by image fusionacquired. For the gadolinium enhanced dynamic study,a multiphase dynamic study including arterial, portal,and delayed phases was performed before unenhancedMR imaging. The parameters of enhanced studywere as follow: repetition time/echo time, 3.89/1.51ms; number of sections, 52; field of view, 420 mm;matrix, 144 384; flip angle, 25 ; gap, 20%; sectionthickness, 3 mm; one signal acquired. Gadolinium(Primovist; Bayer, Shanghai, China) at 8 mol/kg (0.016mL/kg) was injected through the antecubital vein usinga power injector, followed by a bolus administration of20 ml saline at the same injection rate. An axial T2*weighted image was performed by using the threedimensional (3D) sensitivity-encoding water-excitationmultishot echo-planar (SWEEP) sequence 10 mn later.A commercially available image fusion system (MyLab Twice, Esoate, Genoa, Italy) was used to performMRI-MRI image fusion. One series of MRI imagesbefore RFA with clearly demonstrated hepatic vessels,as well as HCC lesions in the portal vein phase orlate phase, were selected, and the images in DICOMformat were imported into the image fusion system.Another series of MRI images one month after RFAwith clearly demonstrated hepatic vessel and ablativearea in DICOM format were also imported into theimage fusion system. Then, the system automaticallydisplayed 6 pictures in 2 rows; the upper row includedthe transaction, coronal and vertical plane MRI imagesbefore RFA, and the lower row demonstrated thecorresponding MRI images after RFA. The HCC lesionin the MRI before RFA was outlined manually, andthen, a 5 mm AM was set automatically. The systemmarked the HCC lesion and AM using different colors(Figures 1 and 2).Image registration was performed by aligning 2overlaid MRI images with 6 parameters; translationand rotation were performed in 3 reformed planesto maximize image similarity around the HCC lesionand ablation area. The hepatic vein, hepatic arteryportal complex and hepatic contour near the lesionwere used as landmarks for fine adjustments to obtainsatisfactory registration. The pre- and post-RFA MRIimages were then overlapped to assess whether theablative area could cover the HCC lesion and 5 mmAM. If multiple tumors were present in the samepatient, the above image processing of the registrationwas repeated for each tumor. The standards ofcomplete registration include that three correspondinganatomic landmarks adjacent to the tumor were fullymatched, and the offset was less than 5 mm in eachplane. Failure of registration was assigned if the abovestandard was not met after three attempts. The timespent on registration for each lesion was recorded.After image registration, post-RFA image wasfused to the pre-RFA one in three different planes,then the relationship between the tumor/AM andablation zone in three dimensions was clearly observed(Figure 3). Based on the results of the evaluation ofthe RFA procedure by image fusion, the lesions wereTable 1 Clinical characteristic of the study subjects n (%)VariableValueHepatocellular carcinomaAge (mean SD)SexMaleFemaleAFP 200 μg/L 200 μg/LHbsAgPositiveNegativeChild-Pugh classificationABTumor size cm (mean SD)Multiple tumorsYesNoTumor locationLiver segment ⅠLiver segment ⅡLiver segment ⅢLiver segment ⅣLiver segment ⅤLiver segment ⅥLiver segment ⅦLiver segment ⅧBackground liver cirrhosisPresentAbsentn 5250.2 17.546 (88.5)6 (11.5)32 (61.5)20 (38.5)52 (100)0 (0)35 (67.3)17 (32.7)2.0 1.0 (1.0-3.1)10 (19.2)42 (80.8)0 (0)3 (4.8)7 (11.3)7 (11.3)9 (14.5)11 (17.7)12 (19.4)13 (21.0)46 (88.5)6 (11.5)who had at least 5 years of experience with theRFA procedure. For early evaluation of the possiblecomplications, ultrasound examination was performedwithin 24 h after ablation.Image fusion procedureBefore and one month after RFA, contrast-enhancedMRI was performed for all the patients using a 1.5-TMR imaging unit (Gyroscan Intera; Philips MedicalSystems, Best, The Netherlands). If MRI at one monthafter RFA showed that the lesion had been completelyablated, AM was further evaluated using MRI-MRIimage fusion.All MR imaging was performed by using a 1.5T MR scanner (Signa Excite; GE Medical Systems,United States) with an 8-channel torso phased-arraycoil. Imaging included an axial T1-weighted fast fieldecho (FFE), axial T2-weighted single-shot turbo spinecho (SSTSE), axial in-phase and out-phase chemicalshift GRE T1-weighted images, and a gadoliniumenhanced dynamic study. The parameters of FFEwere as follow: repetition time/echo time, 129/238and 476 ms; number of sections, 60; field of view,380 mm; matrix, 158 256; flip angle, 70 ; gap,15%; section thickness, 3 mm; two signals acquired.The parameters of SSTSE were as follow: repetitiontime/echo time, 2100/84 ms; number of sections, 60;field of view, 350 mm; matrix, 207 384; flip angle,150 ; gap, 10%; section thickness, 3 mm; one signalWJG www.wjgnet.com5347May 7, 2015 Volume 21 Issue 17

Wang XL et al . Ablative margin assessed by image fusionABCFigure 1 Outlined tumor (blue line) in the magnetic resonance imaging images is displayed in different planes. A, B, C: The coronal, transaction and verticalplanes.ABCFigure 2 Ablative margin (yellow line) of 5 mm around the tumor is displayed automatically in the image fusion system. A, B, C: The coronal, transaction andvertical planes.ABCFigure 3 Ablation zone completely covering the tumor and the ablative margin is displayed on the three distinct dimensions in the image fusion system. A,B, C: The coronal, transaction and vertical planes.divided into two groups: (1) the tumor and AM werecompletely covered by the ablation zone (group A);and (2) the tumor was completely covered by theablation zone but an AM was not ensured (group B). Todescribe the position of the unachieved AM, the tumorwas divided into 8 quadrants by three orthogonalplanes (axial, coronal and vertical planes) crossing atthe center of the tumor. The 4 cephaled quadrants ofthe 8 total quadrants were numbered 1-4, and the4 caudal quadrants were numbered 5-8, both in aclockwise direction. The time spent on evaluating theAM for each lesion was recorded.3 mo after the first year. LTP was diagnosed whena follow-up MRI or CT revealed the developmentof the tumor adjacent to the ablative area witharterial hypervascularity and wash-out in the early ordelayed venous phase. The LTP position was recordedaccording to the 1-8 quadrants mentioned above. Theunachieved AM and LTP were considered consistentwhen they were observed in the same quadrant.Statistical analysisThe patient data were exported into Microsoft Excel,where the mean SD was calculated. Statisticalanalyses were performed using the commerciallyavailable SPSS software package version 13.0 (SPSS,Inc, Chicago, IL). Categorical variables were compared2using χ test. All P-values were two sided. Thedifference was considered significant at P 0.05.Follow-up procedureThe patients were followed every 2 mo in the firstyear after RFA by CEUS, contrast-enhanced MRI or CT.Then, the follow-up interval was extended to everyWJG www.wjgnet.com5348May 7, 2015 Volume 21 Issue 17

Wang XL et al . Ablative margin assessed by image fusionOne of the major impacting factors on the thera peutic effectiveness of ablation for HCC is LTP, whichis primarily ascribed to insufficient AM. Therefore,the assessment of AM plays an important role in RFA[16-18]scheduling. If tumors with insufficient AM aredetected in a timely manner using precise imageevaluation, an effective method could be implementedto improve the therapeutic effectiveness or determinewhether closer follow-up is required. Traditional imageevaluation methods, including CEUS and side-by-sidecomparison with CT/MRI images, cannot quantitatively[19,20]determine the AM in three dimensions.In previous studies, the results of CT image fusionwith a CT workstation demonstrated the feasibility ofthe image fusion technique in the assessment of the[21,22]RFA procedure for HCC. In this study, we used acommercially available ultrasound workstation for theMRI-MRI image fusion before and after RFA. Of the62 lesions in 52 HCC patients, the image fusion failedin only one case due to the significant deformation ofthe liver and massive ascites after RFA. The successrate of MRI-MRI image fusion was 98.4% (61/62). Thetotal time required for the creation of fusion imageswas approximately 15 min in 40 all cases. The successrate of the MRI-MRI image fusion was similar to those[21,22]based on other image fusion methods.In the new image fusion system, an AM aroundthe tumor and the performed image fusion after theimage registration could be determined. The systemautomatically and simultaneously displays the ablativezone and AM in the same fusion image. Thus, whetherthe AM was achieved in all directions could be directlyand easily assessed.Similar to the other image fusion techniques,the accuracy of the MRI-MRI image fusion in thisworkstation was also dependent on the quality ofthe MRI volume data. To reduce the influence of liverdeformation, the interval between RFA and subsequentcollection of follow-up image data should be limited.To enhance the consistency of consecutive MRIlocalization, respiratory gating and image matchingtechniques can be adopted to reduce the influence ofrelative movement of the abdominal organs.Our study demonstrated that the frequency of LTPin patients without a 5 mm AM was significantly higherthan that in those with a 5 mm AM. All LTPs occurredin the section in which the AM was not confirmed. Inone case, the fusion image showed that the tumorwas not included within the ablation zone after the firstRFA intervention, and this case exhibited incompleteablation. A second RFA session combined with TACEwas performed in this patients. In this second session,the tumor was completely ablated, however still, thethAM could not be ensured at the 5 district. Therefore,we closely followed the patient and detected LTP in theunachieved AM area 4 mo later. Another session of RFAcombined with TACE was performed on the patient.Our results demonstrated that the MRI-MRI imagefusion technique could precisely describe the directionRESULTSMRI-MRI image fusion was accurately achieved in 61of the 62 tumors; the case without fusion was dueto significant deformation of the liver and massiveascites after RFA. The success rate of MRI-MRI imagefusion was 98.4% (61/62). Examples of the imageregistration and MRI-MRI image fusion before andafter RFA are shown in Figures 1, 2 and 3. The totaltime required for the creation of image fusion was 15.5 5.5 min (range: 8-22 min) in all cases.At one month after RFA, MRI revealed that 61 ofthe 62 tumors had been completely ablated. Anotherses

magnetic resonance imaging (MRI)-MRI image fusion in assessing the ablative margin (AM) for hepatocellular carcinoma (HCC). METHODS: A newly developed ultrasound workstation for MRI-MRI image fusion was used to evaluate the AM of 62 tumors in 52 HCC patients after radiofrequency ablation (RFA). The lesions were divided into two

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