Upsala Journal of Medical Sciences. 2013; 118: 91–97 ORIGINAL ARTICLE Whole-body MRI including diffusion-weighted imaging compared to CT for staging of malignant melanoma FIRAS MOSAVI1, GUSTAV ULLENHAG2 & HÅKAN AHLSTRÖM1 1Department of Radiology, Uppsala University Hospital, Uppsala, Sweden, and 2Department of Oncology, Uppsala University Hospital, Uppsala, Sweden Abstract Background.Whole-body(WB)magneticresonanceimaging(MRI),includingdiffusion-weightedimaging(DWI),hasbeen increasingly used for the detection of metastatic disease. Purpose.ToassessthevalueofWBMRIincludingDWIcomparedtocomputedtomography(CT)forstagingofmalignant melanoma.AsecondaimwastoassessthevalueofDWIinadditiontoconventionalMRsequencesforthedetectionoflesions. Materialandmethods.WBMRIwithDWIandCTchest,abdomen,andpelviswereperformedin23patientswithhistologically confirmed malignant melanoma. CT before and after the MRI examinations and the clinical follow-up was utilized as the standard of reference. Results.WBMRIandWBDWIdetected345and302lesions,respectively,comparedto397lesionswithCT.Thesensitivityof WBMRIandWBDWIvariedconsiderablyindifferentregionsofthebody.Inthelungs,WBMRIandWBDWIshowed63% and 47% true-positive lesions, respectively. WB MRI and WB DWI detected 56 bone lesions in 12 patients compared to 42lesionsin8patientswithCT.Inaddition,WBMRIandWBDWIcoulddetect68lesionsoutsidethefieldofviewofCTin six patients. Conclusion. WB MRI is still not ready to replace CT for staging of malignant melanoma, especially in the thorax region. However, WB MRI is advantageous for detection of bone lesions and lesions outside the investigated volume of the conventional CT. When WB MRI is evaluated, both DWI and conventional MRI sequences must be scrutinized. Key words: DWI, malignant melanoma, whole-body MRI Introduction Recent breakthroughs in DWI technology and especially the development of parallel imaging tech- Whole-body (WB) magnetic resonance imaging niques have facilitated WB diffusion scanning. In (MRI) with diffusion-weighted imaging (DWI) has 2004, Takahara et al. reported a new WB DWI recently been introduced for the evaluation of multi- technique, called ‘diffusion-weighted whole-body focal metastases in oncology patients. DWI reflects imaging with background body signal suppression’ themovementofwatermoleculesinbodytissuesdue (DWIBS). This method deliberately uses scanning totheirrandomthermalmotion.Restrictionofwater during free breathing to detect lesions in (moving) diffusion is inversely associated with the integrity of visceral organs (3). These advances in DWI offer a cell membranes and tissue cellularity (1). DWI pro- wide range of potential applications in whole- vides functional information and can be utilized for body oncology imaging. The combination of the detection and characterization of pathologic pro- functional data from DWI and detailed anatomic cesses,notonlyforacutecerebralinfarction,butalso information given by conventional MR sequences for malignant tumors (2). such as T1, T2, and short-tau inversion recovery Correspondence:FirasMosavi,DepartmentofRadiology,UppsalaUniversityHospital,SE-75185Uppsala,Sweden.Fax:+46-18-6114806. E-mail:fi[email protected] (Received20December2012;accepted14February2013) ISSN0300-9734print/ISSN2000-1967online(cid:1)2013InformaHealthcare DOI:10.3109/03009734.2013.778375 92 F. Mosavi et al. (STIR)isbelievedtoprovidefurtherimprovementin Netherlands). The whole body (from head to toe) tumor staging. was covered with an in-built whole-body coil. Seven Imaging plays a critical role in staging of patients stations were included, with three sequences in each with malignant melanoma (4). The prognosis of station: 1) Coronal T1-weighted spin echo (T1W) malignant melanoma is strongly associated with the sequencewithbreath-holdinginabdomenandthorax; stagingatthetimeofdetection(5).Sofar,thestaging 2) Coronal fat-suppressed T2-weighted STIR (T2W- evaluations of metastatic malignant melanoma STIR) sequence with respiratory triggering in thorax demandvariousmodalitiessuchascomputedtomog- and abdomen; and 3) DW imaging performed in raphy(CT),MRI,andpositronemissiontomography/ transversal plane during free breathing using b-value computedtomography(PET/CT)(4).Thisapproach of 1000 and 0 mm2/s. High-resolution 3D-maximum is excessive and time-consuming. Whole-body, i.e. intensity projection images (MIP) of the whole body head to toe, techniques like WB MRI and PET/CT were reconstructed from the transversal diffusion can be optimal procedures to evaluate the tumor images. spread in a single examination. The benefits of WB In addition to the sequences above, transversal MRI,suchasitslackofionizingradiationandwhole- T2-weighted turbo spin echo (T2W-TSE) and T1- bodycoverage,makeitaveryattractivecandidatefor weighted gradient echo (T1W-GE) in- and out-of- evaluationofdistantmetastasesincancerpatients.To phase sequences of the abdomen and thorax were date there are few data assessing WB MRI including performed for further evaluation of suspected DWI for staging of malignant melanoma (6). It is lesions. The investigations were performed without unclear whether DWI can detect all the lesions that intravenous contrast agent administration. are detected in conventional MR sequences. Totalexaminationtimewasapproximately50min- Themainaimofthisstudywastoassessthevalueof utes. The imaging parameters are summarized whole-body, i.e. head to toe, MRI including DWI, in Table I. comparedtoclinicalroutineCTforstagingofmalig- nantmelanoma.Asecondaimwastoassessthevalue CT chest, abdomen, and pelvis of WB DWI in addition to conventional MR images for the detection of malignant melanoma lesions. The CT examinations were performed with conven- tionalspiraltechnologyand3mmslicethicknessfrom Material and methods the root of the neck to the upper part of the thighs as partofroutineclinicalcarebydifferentscanners.Except Patients foronepatientwhowasallergictointravenouscontrast, the other patients underwent examination after in- Between March 2008 and April 2011, 23 patients jection of intravenous contrast in chest, abdomen, (14menand9women)withameanageof57.6years and pelvis. (range18–87years)wereincludedinthisprospective study.Bothpreviouslytreatedanduntreatedpatients were included. Evaluation of MR and CT imaging The patients were referred from the oncology WB DWI and WB MRI were first evaluated by two department after being informed about the study experienced radiologists in consensus, blinded from procedures. The study was approved by the ethics theCTexaminations.Then,CTimages(chest,abdo- committee.ThepatientsunderwentWBMRIinclud- men, and pelvis) were evaluated by one of the ing DWI and CT chest, abdomen and pelvis. The radiologists with access to the clinical report. interval time between WB MRI and CT was Finally, the MR and CT images were reviewed 1–13 days (mean 3.5 days). Follow-up CT examina- together on a lesion-by-lesion basis, and correlating tions were also performed in each patient. and non-correlating lesions between the modalities Inclusion criteria consisted of histologically con- were noted. Additional lesions in MRI outside the firmed malignant melanoma with evidence of distant investigated CT volume were also reported. These metastasesinpreviousstudies.Exclusioncriteriawere comparative analyses were performed by the two the usual contraindications for performing of MRI radiologists in consensus. suchasclaustrophobia,metaldevicesinthebody,and The WB MRI examinations were analyzed by two pacemaker. differentapproaches.Inthefirstapproach,calledWB DWI,diffusion-weightedimageswereevaluatedstart- Whole-body MRI ing with review of maximum intensity projection All WB MRI examinations were performed on a (MIP)imagestogetanoverviewofsuspectedlesions. 1.5 T system (Gyroscan Intera, Philips, Best, The The lesion was then verified by analyzing transversal Whole-body MRI and CT for staging of malignant melanoma 93 Table1. MRimagingsequenceprotocol. Imagingparameters T1Wimaging T2-STIRimaging DWI Sequencetype Turbospinecho Turbospinecho Echoplanarimaging TR/TE/TI 324/17.5/0 2758/64/165 3257/70/180 Slicethickness/gap(mm) 6/1 6/1 6/0 No.ofslicesperstation 33–45 33–45 44 Fieldofview(mm) 265(cid:1)530 265(cid:1)530 374(cid:1)530 Matrix 208(cid:1)287 120(cid:1)336 112(cid:1)74 Bandwidth/pixel(hertz) 485.6 496 20.4 Scan/station(s) 60 50 142 No.ofsignalaverages 1 2 2 B-values/mm2 0and1000 TR=repetitiontime;TE=echotime;TI=timeinversion. WBDWIsusingb-valueof1000mm2/s.Ab-valueof Results 0 mm2/s was also used to rule out T2-shine-through effectandtoacquireanatomicaldetails.IntheDWI,a CT examinations were able to identify 397 lesions, lesionwasdefinedasafocalareawithequalorhigher whereas WB MRI and WB DWI detected 345 and signal intensity than the organ with highest signal 302 lesions, respectively (Table II). In patient-based intensity in each investigated region, e.g. the brain analysis, lung lesions were found in 13/16 (81%) in the neck region and the bone-marrow in other patients with WB MRI and in 11/16 (68%) patients regions (7). Positive findings on DWIs had to be with WB DWI. In liver, WB MRI and WB DWI confirmedonwhole-bodyT1-andT2-STIR-weighted detectedlesionsin12/12(100%)patients(TableIII). imaging. Two patients showed lesions in the spleen which In the second approach, called WB MRI, T1- could not be detected with WB DWI but could be weightedandT2-STIRimageswereevaluatedtogether identified both with CT and conventional MRI. with DWI. In lesion-based analysis, WB MRI and WB DWI The presence of malignancy on CT and MRI was showed63%and47%true-positivefindingsinlungs, based on conventional morphological and contrast respectively (Figure 1). WB MRI and WB DWI enhancement criteria. A lymph node was considered showed 90% and 81% true-positive lesions in the asmetastasisifitsshortaxisdiameterwasgreaterthan liver (Table III). An equal number of abdominal 1 cm and its shape was round (8). andaxillary lymphnodes andsubcutaneous metasta- The long axis diameter of each lesion, except for ses were detected with WB MRI, WB MRI, and CT lymphnodes,wasmeasuredonCTandconventional (Table III).WB DWI showed similar results as WB MR images. The lesions were sorted into three MRIindetectionoflesionsoutsideoftheCTfieldof groups: 1) 0.5 cm and less; 2) 0.6–0.9 cm; and 3) view. 1 cm and above. WB MRI and WB DWI detected a significantly Standard of reference: Each patient underwent highernumberofbonelesionscomparedtoCT.WB several CT examinations both before and after the MRI and WB DWI detected equally 56 bone lesions MRIexaminations,andtheseexaminationswereused in 12 patients, while CT showed 42 bone lesions in as the standard of reference. 8 patients (Figure 2). CTandWBMRIdetected14versus4lesionswith Statistics size 0.5 cm and less, 84 versus 38 lesions with size 0.6–0.9 cm, and 299 versus 303 with size 1 cm and Pathological findings in each patient were analyzed above. separately in WB MRI and WB DWI compared to In addition, WB MRI and WB DWI could both the standard of reference. Patient- and lesion- detect68lesionsoutsidethefieldofviewofCTinsix based analyses were performed, and the results patientsasfollows:5brainmetastasesintwopatients, were reported as true-positive, false-positive, and 27 bone lesions in six patients, 19 subcutaneous false-negative; true-negative findings could not be lesions in four patients, 16 lymph node metastases analyzed due to the constraining definition of posi- inthreepatients,and1lesionintheparotidglandsin tive lesions in this study. one patient (Figure 3). 94 F. Mosavi et al. Table2. Assessmentofmalignantmelanomametastasesin23patientswithDWI,allWBMRsequences,aandCTthorax,abdomenand pelvis. DWI AllMRsequencesa CT Siteofmetastasis Lesions Patients Lesions Patients Lesions Patients Liver 53 12 59 12 65 12 Spleen 0 0 11 2 11 2 Lung 60 11 81 13 127 16 Bone 56 12 56 12 42 8 Lymphnodesinabdomen 71 14 71 14 71 14 Lymphnodesinthoraxb 18 10 23 12 37 13 Axillarylymphnodes 11 5 11 5 11 5 Subcutaneousmetastases 33 6 33 6 33 6 aT1W,T2-STIR,andDWI. bDefinedasmediastinumandhilarregions. Discussion positive findings in MRI compared to CT images. MRI is known to have a very high sensitivity and Our prospective study shows that the sensitivity of specificity in detection of bone metastases (10-13). WBMRIandWBDWIvariesconsiderablyindiffer- Müller-Horvatetal.showedthesuperiorityofWB ent regions of the body. WB MRI and WB DWI MRI,withoutDWI,overCT(exceptforlunglesions) detected fewer lesions in the thorax region, i.e. lung indetectionofmetastasesfrommalignantmelanoma. lesionsandenlargedlymphnodesinthemediastinum MRI could change the treatment decision in 24% of and hila, compared to CT. The difficulties in evalu- patients(14).Furthermore,MRIwasfoundtodetect ation of thorax by WB MRI may be due to the morelesionsinliver,spleen,subcutaneoustissue,and presence of cardiac and respiratory motion artifacts muscle, while in our study we had rather similar in this region. Respiratory-triggered or breath-hold results from CT and WB MRI including DWI in techniquesmayimprovetheresultsofWBDWIinthe these regions. The reason for the better results in thorax region (9). that study compared to our study is probably the WBMRIandWBDWIprovedtohaveapotential use of intravenous MR contrast agent. Liver-specific inthedetectionofmetastasesintheabdominalregion MR contrast is especially important for detection of and especially in the skeleton. Bone lesions were liver metastases. excluded from the analysis in Table III because the Laurentetal.comparedWBMRI,includingDWI results would falsely show a high rate of false- and PET/CT, showing higher sensitivity and Table3. Lesion-andpatient-basedanalysisofallMRIsequencesandDWIinevaluationofmetastasesfrommalignantmelanoma,compared toCTimages. Lesion-basedanalysis Patient-basedanalysis DWI AllMRIsequencesa DWI AllMRIsequencesa Siteofmetastases TP FP FN TP FP FN TP FP FN TP FP FN Liver 81% 0 19% 90% 0 10% 100% 0 0 100% 0 0 Spleen 0 0 100% 100% 0 0 0 0 100% 100% 0 0 Lung 47% 0 53% 63% 0 37% 68% 0 32% 81% 0 19% Lymphnodesinthorax 48% 0 52% 62% 0 38% 77% 0 23% 92% 0 8% Lymphnodesinabdomen 100% 0 0 100% 0 0 100% 0 0 100% 0 0 Axillarylymphnodes 100% 0 0 100% 0 0 100% 0 0 100% 0 0 Subcutaneousmetastases 100% 0 0 100% 0 0 100% 0 0 100% 0 0 aT1W,T2-STIR,andDWI. DWI=Diffusion-weightedimaging;TP=True-positive;FP=False-positive;FN=False-negative. Whole-body MRI and CT for staging of malignant melanoma 95 WBMRIgeneratesalotofdataandimages,anda simplifiedapproachforanalysisisneeded.Therefore, we wanted to assess whether all lesions were seen in the DWI MIP images. DWI using MIP images can highlight the metastatic lesions, which facilitates the overall evaluation of tumor spread (Figure 3). Each lesion should then be verified with axial DWI and conventional MR images. According to our study results, the evaluation ofWB MRI must also include a b the scrutiny of conventional MRI such as T1 and STIR images for detection of additional lesions. It must be emphasized that our whole-body protocol, due to time limitation, differs considerably from a dedicated regional MRI examination which has sig- nificantly higher accuracy in the detection of lesions. However, there was no difference between WB MRI and CT in grade of staging of malignant melanoma. There were some limitations in our study. Firstly, we could not verify the pathologic findings by biopsy forpracticalandethicalreasons.Secondly,wedidnot evaluate DWI completely separated from other MR ccc d sequences.Wechosethiswayofinterpretationsince, Figure 1. A 66-year-old man with multiple malignant melanoma apart from malignant tumors, artifacts and anumber metastases.TheCTimage,coronalreconstruction,showedalesion of benign lesions and normal anatomical structures intherightlung(arrow)measuringapproximately7mminlongest likespleenandprostatealsoshowhighsignalintensity diameter(a).ThelesionwasnotdetectableonSTIRandT1images (bandc).Thelesioncouldnotbedetectedoncoronalmaximum intensity projection (MIP) DWI image (d). The lesion was not detectedonaxialDWI(notshown). specificity for WB MRI in detection of metastases from malignant melanoma (6). In that study, DWI enabled the detection of an additional 20% lesions compared to conventional MRI protocol and also proved to be the most accurate sequence for detec- tion of metastases in the liver, bone, subcutaneous, and intraperitoneal region. The better results of DWIinthatstudycomparedtoourstudycanpartly dependonthedifferentdiffusionfactorsofb=0and 600 compared to b = 0 and 1000 in our study. Another difference in DWI was that in the Laurent et al. study phased-array surface coil was used with Siemens equipment, while we used Philips equip- ment with in-built whole-body coil and the DWIBS technique. a b c We used CT thorax, abdomen, and pelvis as the comparison modality since PET/CT has a limited availability. CT is at present the most widely applied imaging modality in tumor staging, follow-up, and d evaluation of therapeutic response in patients with malignant melanoma (15). However, malignant mel- Figure2. A64-year-oldmanwithmalignantmelanomaandmul- anoma metastases can be located anywhere in the tiple metastases. A bone lesion (arrow) measuring approximately body. 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