Diffusion-weighted whole-body imaging with background body signal suppression/t2-weighted image fusion of gastrointestinal cancers

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1 44 Diffusion-weighted whole-body imging with bckground body signl suppression/t2-weighted imge fusion of gstrointestinl cncers MINORU TOMIZAWA 1, FUMINOBU SHINOZAKI 2, KAZUNORI FUGO 3, TAKAFUMI SUNAOSHI 2, DAISUKE KANO 2, SATOMI TANAKA 2, AIKA OZAKI 2, ERIKO SUGIYAMA 2, MISAKI SHITE 2, RYOUTA HAGA 2, AKIRA BABA 2, YOSHIYA FUKAMIZU 2, TOSHIYUKI FUJITA 2, SATOSHI KAGAYAMA 2, RUMIKO HASEGAWA 4, AKIRA TOGAWA 4, YOSHINORI SHIRAI 4, NOBORU ICHIKI 4, YASUFUMI MOTOYOSHI 5, TAKAO SUGIYAMA 6, SHIGENORI YAMAMOTO 7, TAKASHI KISHIMOTO 3 nd NAOKI ISHIGE 8 Deprtments of 1 Gstroenterology nd 2 Rdiology, Ntionl Hospitl Orgniztion Shimoshizu Hospitl, Yotsukido, Chib ; 3 Deprtment of Moleculr Pthology, Chib University Grdute School of Medicine, Chib, Chib ; Deprtments of 4 Surgery, 5 Neurology, 6 Rheumtology, 7 Peditrics nd 8 Neurosurgery, Ntionl Hospitl Orgniztion Shimoshizu Hospitl, Yotsukido, Chib , Jpn Received Jnury 11, 2016; Accepted April 27, 2016 DOI: /mco Abstrct. Diffusion weighted whole-body imging with bckground body signl suppression (DWIBS) yields positive results for cncer ginst the surrounding tissues. The combintion of DWIBS nd T2-weighted imges (DWIBS/T2) in the dignosis of gstrointestinl trct cncers ws retrospectively nlyzed in the present study. Ptients were subjected to mgnetic resonnce imging fter cncer ws dignosed through specimens obtined vi biopsy or endoscopic mucosl resection. Sixteen ptients were ssessed between July, 2012 nd June, 2013 nd the correltion between detection with DWIBS/T2 nd T stging ws nlyzed. Regrding ptients who underwent surgery, the correltion between detection with DWIBS/T2 nd the dimeter or depth of invsion ws nlyzed. All cncers tht hd dvnced to >T2 stge were detectble by DWIBS/T2, wheres ll cncers stged s <T1 were not (P<0.0001). Tumors tht were undetected by DWIBS/T2 hd men dimeter of 1.53±0.25 cm, wheres those detected hd men dimeter of 3.63±1.88 cm; however, the difference ws not sttisticlly significnt (P=0.1053). Cncers invding beyond the musculris propri were detectble by DWIBS/T2, while those which hd not invded the mucos were not (P=0.0476). In conclusion, DWIBS/T2 ws ble to positively identify gstrointestinl trct Correspondence to: Dr Minoru Tomizw, Deprtment of Gstroenterology, Ntionl Hospitl Orgniztion Shimoshizu Hospitl, Shikwtshi, Yotsukido, Chib , Jpn E mil: nihminor cib@umin.c.jp Key words: diffusion weighted whole-body imging with bckground body signl suppression, T2-weighted imge, dimeter, depth of invsion cncers t n dvnced stge (>T2) or invding beyond the musculris propri. Introduction Endoscopy is the gold stndrd for dignosing cncers of the gstrointestinl trct, including the esophgus, stomch, colon nd rectum (1,2). However, endoscopy is not suitble for evluting the depth of invsion nd extent of cncer, s it only llows observtion of the lumen. Endoscopic ultrsonogrphy (EUS) nd contrst enhnced computed tomogrphy (CE-CT) re performed to ssess the structure of the primry lesion, the depth of invsion into the surrounding tissues nd distnt metstsis (3,4). Assessing the depth of invsion my occsionlly be difficult due to the wek contrst of the cncer ginst the surrounding tissues. Therefore, n imging modlity with strong signl nd contrst would fcilitte the ssessment of the depth of tumor invsion. Mgnetic resonnce imging (MRI) is not s populr s CT due to blurring nd low sptil resolution (5). However, MRI my be promising method if strong soft tissue contrst in the bdomen cn be chieved. Diffusion weighted wholebody imging with bckground body signl suppression (DWIBS) imges re cquired using multiple signl verging, pre pulse ft suppression nd hevy diffusion weighting during free brething (6). DWIBS is bsed on diffusion weighted imging (DWI) tht visulizes nd ssesses the rndom movement of wter t the moleculr level (Brownin motion) (7,8). An dvntge of DWIBS is tht it provides strong contrst of cncerous ginst surrounding non cncerous tissues, which is useful for the detection, stging nd monitoring of the response to therpy (9). A mjor limittion of DWIBS is tht ntomicl nlysis my be difficult t times (10,11). Fusion imges of DWIBS nd T2-weighted imges (T2WI (DWIBS/T2) re creted by overlpping DWIBS

2 TOMIZAWA et l: DWIBS/T2 IMAGING OF GASTROINTESTINAL TRACT CANCER 45 Tble I. Pulse sequences used in the present study. Prmeters T1-weighted imge T2-weighted imge DWI (DWIBS/T2) Echo GRE Single shot SE EPI SE TR (msec) Shortest 1,000 11,250 TE (msec) First: 2.3 (out phse), second, 4.6 (in phse) Flip ngle ( ) NSA Slice thickness (mm) Slice gp Ft sturtion None None SPAIR Phse encoding direction Posterior nterior Posterior nterior Posterior nterior DWI, diffusion weighted imge; DWIBS/T2, diffusion weighted whole-body imging with bckground body signl suppression/t2-weighted imge fusion; GRE, grdient echo; SE, spin echo; EPI, echo plnr imging; SPAIR, spectrl ttenuted inversion recovery; TR, repetition time; TE, echo time; NSA, number of signl verges. with T2WI using worksttion (9,12,13). DWIBS/T2 therefore clerly illustrtes functionl informtion in ntomicl imges. In the present study, the performnce of DWIBS/T2 in the dignosis of gstrointestinl cncers ws retrospectively nlyzed. Ptients nd methods Ethicl sttement. The present study ws pproved by the Ethics Committee of the Ntionl Hospitl Orgniztion Shimoshizu Hospitl (Yotsukido, Jpn). This ws not considered clinicl tril, s the procedures were performed s prt of routine clinicl prctice. Written informed consent ws obtined from ll ptients who were subjected to MRI, upper gstrointestinl endoscopy, colonoscopy nd CE-CT. Consent ws obtined from ptients who were subjected to bdominl ultrsonogrphy, but written form ws wived. Written informed consent for inclusion into the study ws lso wived, s ptient records were nonymized nd retrospectively nlyzed. Study design. Ptient records, including imging, from July, 2012 until June, 2013 were retrospectively nlyzed. The ptients were subjected to upper gstrointestinl endoscopy to investigte bdominl pin, nemi, hemtemesis nd other symptoms suggesting diseses of the esophgus, stomch or duodenum. The ptients were subjected to colonoscopy for the investigtion of bdominl pin, melen nd other symptoms suggesting diseses of the colon or rectum. A proportion of the ptients hd been subjected to upper gstrointestinl endoscopy nd colonoscopy s prt of screening. The ptient inclusion criteri were s follows: i) Pthologicl dignosis of esophgel, gstric or colon cncer bsed on bioptic or endoscopic mucosl resection specimens; ii) vilble DWIBS/T2 imges. A totl of 8 men (men ge, 71.6±12.5 yers; rnge 67-77) nd 8 women (men ge, 71.6±4.0 yers; rnge, 46-82) were enrolled in the present study. The depth of invsion nd tumor dimeter were ssessed bsed on specimens obtined through surgery or endoscopic mucosl resection. T stging ws performed using CE-CT, bdominl ultrsonogrphy or EUS, ccording to the 7th edition of the Americn Joint Committee on Cncer clssifiction (14). MRI. All MRI studies were performed using 1.5 Tesl scnner (Achiev, softwre version 3.2.2, Philips Medicl Systems, Best, The Netherlnds). T1-weighted imge (T1WI), T2WI nd DWI were obtined with pulse sequences, s depicted in Tble I. DWIBS/T2 imges were constructed with Extended MR WorkSpce (Philips, Best, The Netherlnds). The DWI grdients were pplied long the X, Y nd Z xes before nd fter 180 inversion pre pulse to obtin ft sturted, isotropic imges with DWI sensitivity using the following prmeters for single stck: b vlue, 0 mm 2 /sec nd 800 mm 2 /sec; repetition time/echo time/inversion recovery, 6,960/79/150 msec; cquisition mtrix, 176x115; nd reconstruction mtrix, 256; field of view: Right/left, 530 mm; nterior/posterior, 349 mm; nd feet/hed, 226 mm; slice thickness, 6 mm; size of reconstructed voxel, 2.07x2.08x6 mm 3 ; 4 verges. One rdiologist nd one gstroenterologist nlyzed the DWIBS/T2 imges. To rule out T2 shine-through or differentite mlignnt lesions from non mlignnt cuses of restricted diffusion, positive pprent diffusion (ADC) mp ws determined s decresed signl on the ADC coefficient with ADC reduction (15). Upper gstrointestinl trct endoscopy, EUS nd colonoscopy. The endoscopic devices used in the upper trct were the GIF N260H, GIF XP260NS, GIF PG260, GIF XQ260 nd GIF Q260 (Olympus, Tokyo, Jpn). EUS ws performed using GF UCT260 (Olympus). The devices used for colonoscopy were the CF Q260 nd PCF Q260AI (Olympus). Sttisticl nlysis. One wy nlysis of vrince or the Chi squred test were pplied using JMP softwre (SAS Institute, Cry, NC, USA). Vlues re expressed s the men ± stndrd devition. Results Ptient chrcteristics. The ptient detils nd dignoses re summrized in Tble II. Gstrointestinl trct cncers were

3 46 Tble II. List of ptients dignosed with cncer. Ptient Depth of Dimeter number Dignosis T stge invsion (cm) T1W T2W DWI DWIBS/T2 1 Esophgel cncer 3 NA NA ( ) ( ) (+) (+) 2 Gstric cncer 1 M 1.5 ( ) ( ) ( ) ( ) 3 Gstric cncer 1 M 1.3 ( ) ( ) ( ) ( ) 4 Gstric cncer 1 M 1.8 ( ) ( ) ( ) ( ) 5 Gstric cncer 2 MP 4 ( ) ( ) (+) (+) 6 Gstric cncer 3 SS 1.3 ( ) ( ) (+) (+) 7 Gstric cncer 4 NA NA ( ) ( ) (+) (+) 8 Gstric cncer 3 NA NA ( ) ( ) (+) (+) 9 Gstric cncer 3 NA NA ( ) (+) (+) (+) 10 Gstric cncer 3 NA NA ( ) ( ) (+) (+) 11 Gstric cncer 3 NA NA ( ) ( ) (+) (+) 12 Gstric cncer 4b SS 5 ( ) ( ) (+) (+) 13 Gstric cncer 3 MP 6 ( ) ( ) (+) (+) 14 Duodenl cncer is NA NA ( ) ( ) ( ) ( ) 15 Duodenl cncer 2 NA NA ( ) ( ) (+) (+) 16 Colon cncer b is M 1.5 (+) (+) (+) (+) Determined ccording to Americn Joint Committee on Cncer clssifiction (7th edition). b Colon polyp subjected to endoscopic mucosl resection. T1W, T1-weighted imge; T2W, T2-weighted imge; DWI, diffusion-weighted imge; DWIBS/T2, diffusion weighted whole-body imging with bckground body signl suppression/t2-weighted imge fusion; NA, not nlyzed; M, mucos; MP, musculris propri; SS, subseros; (+), positive result; ( ), negtive result; is, in situ. initilly dignosed by endoscopy (Fig. 1A). T stging ws performed bsed on CE-CT nd other dignostic imging techniques (Fig. 1B). Colon cncer ws detected by T1WI s it ws polyp protruding into the lumen. T2WI ws positive in one ptient with gstric cncer nd one ptient with colon cncer. A thickened wll ws identified by T1WI nd T2WI in some cses; however, it ws difficult to dignose the other lesions s cncerous, s their intensities were identicl to tht of the surrounding tissues. A totl of 12 ptients were detected with DWI or DWIBS/T2. DWI nd DWIBS/T2 were more sensitive compred with T2WI lone (Fig. 1C nd D). DWI nd DWIBS/T2 exhibited significnt contrst nd hd the sme sensitivity. With DWIBS/T2 it ws esier to nlyze the strong positive signl in n ntomicl context (Fig. 1E). Three ptients with gstric cncer who were negtive on DWIBS/T2, were found to be stge T1 nd 1 ptient with duodenl cncer who ws negtive on DWIBS/T2, ws stged s Tis. The mechnism underlying the negtive results on DWIBS/T2 is intriguing. The shpe of the positive signl on DWIBS/T2 ws consistent with tht of the surgicl specimen (Fig. 1F). Assocition of detectbility with T stge. Subsequently, we focused on T stging nd the ssocition between tumor detectbility with DWIBS/T2 nd T stge ws nlyzed (Tble III). All cncers stged >T2 were detectble by DWIBS/T2 nd ll cncers stged <T1 were not, clerly indicting tht dvnced cncer stge is significntly ssocited with its detectbility with DWIBS/T2 (P<0.0001). Assocition of detectbility with depth of invsion. The ssocition between the tumor dimeter nd detectbility ws next nlyzed. Dimeters were plotted ginst detection with DWIBS/T2 (Fig. 2). The men dimeter of tumors not detected by DWIBS/T2 ws 1.53±0.25 cm, while tht of detected tumors ws 3.63±1.88 cm; however, the difference ws not sttisticlly significnt (P=0.1053). Furthermore, the ssocition of depth of invsion of the tumors with their detectbility by DWIBS/T2 ws ssessed (Tble IV). All 5 cncers tht hd invded beyond the musculris propri were detected by DWIBS/T2, wheres 3 cses tht hd not invded the mucos were not detected. The depth of invsion ws significntly ssocited with detectbility by DWIBS/T2 (P=0.0476). Colon cncer ws positive on DWIBS/T2, lthough ws confined in the mucos; the cncer ws originlly colon polyp with dimeter of 1.5 cm. Discussion Until recently, DWI or DWIBS with 1.5-Tesl scnner ws considered to be unsuitble for imging of bdominl orgns due to respirtory movement (16 18). However, the protocol of cquiring imges hs improved with the use of respirtory trigger (6). In the present study, ll gstric nd duodenl cncers stged >T2 were detectble by DWI nd DWIBS/T2 (19). DWI nd DWIBS/T2 exhibited strong signl nd contrst ginst the surrounding tissues. For this reson, DWI nd DWIBS/T2 hd better sensitivity when compred with T2WI lone. Unlike endoscopy, DWIBS/T2 my be useful for evluting the extent

4 TOMIZAWA et l: DWIBS/T2 IMAGING OF GASTROINTESTINAL TRACT CANCER 47 Tble III. Correltion between tumor detectbility by DWIBS T2 nd T stge. T stge Detection >T2 <T1 Totl (+) ( ) Totl Determined ccording to the Americn Joint Committee on Cncer clssifiction (7th edition); (+), positive results; ( ), negtive results. P< (Chi-squred test). DWIBS T2, diffusion weighted wholebody imging bckground body signl suppression/t2-weighted fusion imge. Tble IV. Assocition between tumor detectbility by DWIBS T2 nd depth of invsion. Depth of invsion Detection >MP M Totl Figure 1. Representtive imges from ptient with gstric cncer. A 74 yer old womn with significnt vomiting ws subjected to (A) upper gstrointestinl endoscopy, reveling n irregulrly shped ulcer obstructing the pylorus. The ptient's stomch ws filled with fluid nd (B) the wll ner the pylorus ws found to be thickened on contrst enhnced computed tomogrphy. (C) T2-weighted imging nd (D) diffusion weighted whole body imging with bckground body signl suppression (DWIBS) were fused to crete (E) DWIBS/T2 fusion imge showing strong signl in the thickened prt of the gstric wll (rrow). (F) Gstric cncer ws dignosed in the hemtoxylin nd eosin-stined sections from the thickened gstric wll (rrowheds). Scle br, 5 mm. (+) ( ) Totl Colon polyp subjected to endoscopic mucosl resection. >MP, invsion beyond musculris propri; M, invsion confined to mucos; (+), positive results; ( ), negtive results; P= (Chi-squred test). DWIBS T2, diffusion weighted whole-body imging bckground body signl suppression/t2-weighted fusion imge. Figure 2. Plots showing the dimeters of gstric or colorectl cncer in ssocition with detectbility by diffusion weighted whole-body imging bckground body signl suppression/t2-weighted fusion imge (DWIBS/T2). (+), detected by DWIBS/T2; ( ), not detected by DWIBS/T2. nd depth of invsion of gstric cncer (20 22). By contrst, ll gstric nd duodenl cncers exhibiting invsion of <T1 were not detected by DWIBS/T2, indicting tht T stge ffected tumor detectbility by DWIBS/T2. In prticulr, Borrmnn 4 gstric cncer exhibits thickened wll, referred to s sndwich sign (23). Our findings suggested tht DWIBS/T2 my dd dignostic informtion to the process of T-stging (20 22,24). T stging is performed bsed on the depth of invsion regrding gstrointestinl trct cncers. The present study reveled tht cncers confined within the mucos were not detected by DWIBS/T2. One exception ws cse of colon cncer; the ptient presented with colon polyp nd underwent endoscopic mucosl resection. The polyp ws 1.5 cm in dimeter nd protruded into the lumen. It ws hypothesized tht the polyp ws of sufficient size to be detectble by DWIBS/T2, even though the cncer hd only invded the mucos. Of note, ll other cncers tht were not detectble by DWIBS/T2 were flt. Cncers confined within the mucos my be positive on DWIBS/T2 upon reching certin volume. High sptil resolution MRI is ble to detect gstric cncer within the mucos (22). However, this technique is currently not pplied. One limittion of the present study ws the smll number of ptients. Further studies including more colon nd duodenl cncer ptients re required to confirm our findings. Another limittion ws tht tumor invsion of the musculris propri (PM), subseros (SS) nd serosl exposure (SE) ws not nlyzed. In future studies, the possibility to differentite

5 48 between PM, SS nd SE invsion with DWIBS/T2 compred with endoscopic ultrsound should be ddressed (25). In conclusion, DWIBS/T2 ws ble to identify gstrointestinl cncers stged s >T2 or invding beyond the musculris propri. References 1. Allum WH, Blzeby JM, Griffin SM, Cunninghm D, Jnkowski JA nd Wong R; Assocition of Upper Gstrointestinl Surgeons of Gret Britin nd Irelnd, the British Society of Gstroenterology nd the British Assocition of Surgicl Oncology: Guidelines for the mngement of oesophgel nd gstric cncer. Gut 60: , Lbinc R, Nordlinger B, Berett GD, Mosconi S, Mndlà M, Cervntes A nd Arnold D; ESMO Guidelines Working Group: Erly colon cncer: ESMO clinicl prctice guidelines for dignosis, tretment nd follow up. Ann Oncol 24 (Suppl 6): vi64 vi72, Didden P, Spnder MC, Wijnhoven BP, Kuipers EJ nd Bruno MJ: Improving the qulity of pretretment stging in ptients with esophgel crcinom fst trck study. 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