BJR 2015 TheAuthors.Publishedby the BritishInstituteof RadiologyReceived:7 January 2014Revised:29 December 2014Accepted:20 January 2015doi: 10.1259/bjr.20140040Citethis article as:ShimSS, Oh Y-W, Kong KA, Ryu YJ, KimY, Jang DH. Pulmonary nodule size evaluation with chest tomosynthesis and CT: a phantomstudy. Br JRadiol2015;88:20140040.FULL PAPERPulmonary nodule size evaluation with chest tomosynthesisand CT: a phantom study1S S SHIM,2Y-W OH,3K A KONG,4Y J RYU,1Y KIM and1D H JANG1Department of Radiology, Mokdong Hospital, Ewha WomansUniversity School of Medicine, Seoul, Republicof Korea2Department of Radiology, Korea University AnamHospitalandKoreaUniversityCollegeof Medicine,Seoul, Republic of Korea3Clinical TrialCenter, Ewha WomansUniversity Medical Center, Seoul, Republic of Korea4Departmentof Internal Medicine, Mokdong Hospital,Ewha WomansUniversity School of Medicine, Seoul, Republic of KoreaAddresscorrespondence to: Yu-Whan OhE-mail:yuwhan@kumc.or.krObjective: We compared digital tomosynthesis (TOMO) andchest CT in terms of assessing the sizes of nodules located inzones where evaluation by simple radiography is limited.Methods: Atotal of 48 images comprising phantomnodules of four sizes in six different locations were used.Nodule size measurement errors for measurements usingTOMOand CT images compared with the actual size fromeach observer were calculated. The inter- and intra-observer repeatabilityof themeasuredvaluesandtheagreement betweenthetwotechniqueswereassessedusing the method described by Bland and Altman.Results: The mean measurement errors for all of thenodules andfour observers were20.84mm[standarddeviation(SD), 0.60mm]onTOMOand20.18mm(SD,0.71 mm)onCTimages. Themeanmeasurementerrorsfor the different observers ranged from21.11 to 20.55mmfor TOMO andfrom20.39 to 0.08mm for CT.Assessingthe agreement between nodule size measurements usingTOMOandCTresultedinmeanmeasurementerrorsof20.65mm, witha95%limit of agreement of 22.53to1.22mm for comparison of TOMO with CT.Conclusion: Our results suggest that nodule sizes obtainedusing TOMOand chest CT are comparable, even fornoduleslocatedinareaswherethesizemeasurementislimited on simple radiography.Advances in knowledge: TOMOandCTcan be usedinterchangeably, even for nodules located in a blind areaon simple radiography.Solitarylungnoduledetectionhasincreasedowingtothewidespread use of CTimaging. Nevertheless, the mostcommonly used routine examination for lung nodulescontinuestobechestradiography,becauseituseslowra-diationdoses, is economical andis easytouse. Becausechest radiographic images are two-dimensional projectionsof three-dimensional structures, early lung cancer detectionon chest radiographs is often challenging. The projection ofpulmonary vessels, bones and part of the mediastinum onlungeldsoftenpartiallyorcompletelyobscuresthepul-monarynodules, resultinginfailurebytheradiologisttodetectlungnodules.1,2Digital tomosynthesis(TOMO)hasrecentlybeenappliedtochest imagingfor the detectionof subtlenodules onsimpleradiography, withpromisingresults.3,4Ithasbeenintroducedas a modality withthe potential toprovideimages similar to CT but at a comparably reduced cost andradiation exposure.4James et al5reported that 74% of lungnodules$4 mmindiameterthatcanbeidentiedonCTcanalso be detected using TOMO. Vikgrenet al6alsoreported that 92%of nodules $4 mmindiameter aredetectable using TOMO. In 2012, Johnsson et al7comparedthe ability of TOMOand CTto detect nodule size in20patients andfoundthat bothmethods couldbeusedinterchangeablyforthesemeasurements. Thisresult callsfor caution, however, because the limit of agreement (LOA)between the modalities is wider than for the intraobservervariabilityofeachmodality.Basedonthese studies, we hypothesizedthat TOMOiscomparabletoCTimagingfor thedetectionof noduleslocatedinareaswheresizemeasurement islimitedusingsimple chest radiography because of overlapping structures.The purpose of this study was to assess the size de-terminationof noduleslocatedinthesezonesbyTOMOandchestCT.METHODS AND MATERIALSThorax phantom and model nodule preparationThe thorax phantomN1 (Kyoto Kagaku Co., Ltd,Kyoto, Japan) was constructed fromsynthetic materials(i.e. polyurethane, epoxy resin, calciumcarbonate). Modelnodules witha homogeneous compositionof solid-type ure-thane foam nodules of four sizes (3, 5, 8 and 10 mm) were used.Nodules were placed in six lung zones: the right apex, middle ofthe right subpleural lungparenchyma, rightupper hilum, rightlowerhilum, rightdiaphragmaticangleoftheheart(rightcar-diophrenicangle)andtherightlowerretrohepaticlungparen-chyma(Figure1).Chest CTAtotal of48phantomsets, comprising4nodulesizes, 6loca-tions and2imagingmodalities, wereincludedinthepresentstudy. We used a 64-channel CT scanner (Somatom Denitionscanner; Siemens Healthcare, Forchheim, Germany) for chestCT. The scanning parameters were as follows: individual de-tector width, 0.625 mm; gantry rotation time, 0.5 s; tube voltage,120 kVp; tubecurrent, 30 mA; andpitch, 1. Axial imageswerereconstructedusing a sectionof 2 mminthickness, the B70kernel(SiemensHealthcare) anda345-mmeldofview.Digital tomosynthesisTOMOexaminations were performed using a commerciallyavailable unit (Sonialvision Sare II; Shimadzu Co., Kyoto,Japan)withaat-panel detectorsystem. WealteredthedigitalTOMO parameters to establish a lower radiation dose conditionthat was suitable for chest imaging. 74 low-dose projectionimages were acquired within 4.85 s using a tube voltage of120 kVpand0.04 mA. The detector was xedintoposition,whereas the X-ray tube was subjectedtovertical continuousmovement, from220 to 120, around the standard orthogonalposteroanterior position, and image data were acquired. A totalof 74 projection images were obtained from 1 examination andwereusedtoreconstruct 84coronal images witha2-mmre-constructioninterval.Radiation doseFor the radiation dose assessment in TOMO, a dosemeter(UnforsThinXIntra; Unfors Instruments AB, Billdal, Sweden)that was attached to the centre and surface of the chest phantom(N1)recordedtheabsorptiondose. Theabsorbeddoseat thephantomsurface for TOMOwas 0.7 mGy, andthe absorbeddoseatthephantomcentre was0.2 mGy.Pulmonary nodule measurementFour radiologists with 15, 4, 3 and 1 years experience in chestimage interpretation participated in the study. Atotal of48images, comprisingnodulesof4sizesin6differentloca-tions andarrangedinrandomorder bytheViewDEXsoft-ware(S odraAlvsborgs Sjukhus, SahlgrenskaUniversityandUniversityofGothenburg, Gothenburg, Sweden), wereused.Observers were blinded to the location and size of the nodulesin the phantom model (Figure 2). They measured the left-to-right diameter andrecordedthelongest length. Theuseofzoomor enlarge tool was freelyavailable, andthe windowFigure 1. Six locations of phantomnodules: (1) right apex;(2)middleoftherightsubpleural lungparenchyma; (3)rightupper hilum; (4) right lower hilum; (5) right cardiophrenicangle; and (6) right retrohepatic lung parenchyma.Figure 2. Images of the thorax phantom performed with chesttomosynthesis (TOMO) (a, c) and chest CT (b, d) witha phantom nodule (arrows). (a, b) A 3-mm nodule in the rightapexisobservedonTOMO(measuredas2.38mm)(a)andalsonotedonCT(2.28mm)(b). (c, d)A5-mmnoduleinthemiddleof theright subpleural lungparenchymais seenonTOMO (4.36mm) (c) and CT (5.00mm) (d).BJR SSShimet al2 of 8 birpublications.org/bjr Br J Radiol;88:20140040centre/width for CT was 2750/1500 HU, whereas the windowwidthforTOMOwas30004500 HU. Thesevaluesareclin-icallyrelevant.Allofthemeasurementswererepeatedat20-dayintervalstoassessintraobservervariation.Statistical analysisNodulesizemeasurement errors formeasurement onTOMOandCTimages comparedwiththeactual sizefromeachob-server were calculated. The results are presentedas means 6standard deviations (SDs) and 95% condence intervals (95% CI)ofthemean. Fortheinter-andintraobserverrepeatabilityofthemeasured values,theagreementbetweenthetwotechniqueswas assessed using the method described by Bland and Altman.8The 95% LOA was calculated as the mean difference 61.96 SD ofthe difference.RESULTSUponinitial measurement, oneobserver judgedtwoof the3-mm nodules as beingmissedon the TOMO modality; oneobserverjudgedthreeofthe3-mmnodulesasbeingmissedontheCTmodality; whileanotherobserver judgedoneofthese nodules as being missedonCT. Upontheir secondevaluation, one observer judged two of the 3-mm nodules asbeing missed on TOMOand one 3-mmnodule as beingmissedonCT.ThenumberofmeasuredphantomnodulesandmeanrelativeerrorsforCT andTOMOmeasurementsforeachobserverareTable 1. Number of detected nodules, mean relative error and standard deviation (SD) for each observer regarding measurementson tomosynthesis (TOMO) and CT imagesObserver Observer1 Observer2 Observer 3 Observer4TOMO imagesDetected (n) 24 24 24 22Meanmeasurement error (mm) 20.55 20.75 20.94 21.11SD(mm) 0.38 0.22 0.43 0.98CT imagesDetected (n) 24 24 23 21Meanmeasurement error (mm) 0.08 20.36 20.07 20.39SD(mm) 0.28 0.27 0.66 1.16Figure 3. Measurement error for each observer and eachnoduleontomosynthesisimagescomparedwiththeknowndiameter of thenodule. Dashedline(centre) representsthemeanmeasurementerror forallnodules andobservers.Smalldashedlines(topandbottom)representthemeanmeasure-ment error 62 standard deviation.Figure 4. Measurement error for each observer and eachnoduleonCTimagescomparedwiththeknowndiameterofthe nodules. Dashed line (centre) represents the meanmeasurement error for all nodules and observers. Small dashedlines (top and bottom) represent the mean measurement error62 standard deviation.Full paper: Pulmonary nodule sizeevaluation withTOMOand CT BJR3 of 8 birpublications.org/bjr Br J Radiol;88:20140040Figure 5. Plots show (a) manual measurement data from tomosynthesis (TOMO) images for the diameters of all nodules andobserversplottedagainsttheactual sizeand(b)manual measurementdatafromCTimages. Intheplots, the45lineofequalityisdrawntohelpassesstheagreement betweenthemeasurements. Plotsillustratethat theagreement betweenmeasurementsonTOMOandtheactual nodulesizeshowasimilarpatternwiththeagreementbetweenmeasurementonTOMOandCT.BJR SSShimet al4 of 8 birpublications.org/bjr Br J Radiol;88:20140040provided in Table 1. The mean measurement error for all of thenodules and observers was 20.84 mm (SD, 0.60; 95% CI, 20.96to 20.72 mm) on TOMO and 20.18 mm (SD, 0.71; 95% CI,20.33to20.04 mm)onCTimages.Theabsolutemeasurement errors foreachobserver andeachnodule on TOMO and CT images are provided in Figures 3 and4. Onaverage, all of themanual measurementsonbothchestTOMO and CT images underestimated the nodule size, with theexception of one observer using CT. Figure 5 shows the manualmeasurement data from TOMO imagesforthe diameters of allnodules and observers plotted against the actual size and manualmeasurement data fromCTimages. The meanmeasurementerrors for the different observers ranged from 21.11 to20.55 mmfor TOMOandfrom20.39to0.08for CT. ThemeanmeasurementerrorswithanLOAforeachobserverandsizeareprovidedinTable2.The intra- and interobserver 95% LOA for each imaging type areprovided in Table 3. The intraobserver 95% LOA for the diametermeasurements calculated using the mean of the two measurementsas a reference ranged from 20.42 to 0.50mm for the least variableobserver to 21.85 to 2.31 mm for the most variable observer usingtheTOMOmodality. For CTmeasurements, the intraobserverTable 2. Mean measurement error and limit of agreement (LOA) for real size of the nodules by each observer and sizeModality/measurementTOMO CTMeanmeasurementerror (mm)LowerLOA(mm)UpperLOA(mm)Meanmeasurementerror (mm)LowerLOA(mm)UpperLOA(mm)Observer1 20.55 21.29 0.19 0.08 20.46 0.632 20.75 21.19 20.32 20.36 20.89 0.173 20.94 21.78 20.09 20.07 21.37 1.234 21.11 23.02 0.81 20.39 22.66 1.88Size(mm)3 20.63 22.11 0.86 20.72 22.87 1.445 20.64 21.21 20.07 20.00 20.82 0.818 21.14 21.72 20.56 20.05 20.83 0.7410 20.95 22.42 0.52 0.03 20.80 0.85TOMO, tomosynthesis.Table 3. Intra- and interobserver mean measurement error by observerModality/measurementTOMO CTMeanmeasurementerror (mm)LowerLOA(mm)UpperLOA(mm)Meanmeasurementerror (mm)LowerLOA(mm)UpperLOA(mm)Intraobserver1 0.04 20.42 0.50 20.08 20.75 0.582 20.20 20.68 0.28 20.43 21.01 0.163 0.06 20.44 0.57 20.14 21.30 1.034 0.23 21.85 2.31 20.01 22.47 2.45Interobserver1and 2 0.20 20.31 0.71 0.44 20.34 0.221and 3 0.38 20.06 0.83 0.15 21.22 1.531and 4 0.55 21.49 2.59 0.48 21.72 2.672and 3 0.18 20.46 0.83 20.29 21.58 1.002and 4 0.35 21.52 2.22 0.03 22.12 2.193and 4 0.17 22.02 2.36 0.32 21.49 2.13LOA, limit of agreement; TOMO, tomosynthesis.Full paper: Pulmonary nodule sizeevaluation withTOMOand CT BJR5 of 8 birpublications.org/bjr Br J Radiol;88:2014004095%LOA ranged from20.75 to 0.58 mmand 22.47 to2.45mm for the least and most variable observer, respectively.Theinterobserver95%LOA concerningthediameterestimatesfor eachpossible pair of radiologists rangedfrom20.06 to0.83 mmfortheleastvariablepairofradiologiststo22.02to2.36 mmfor the most variable pair of radiologists using theTOMO modality. For measurements using the CT modality, theinterobserver 95%LOArangedfrom20.34to0.22 mmandfrom 22.12 to 2.19 mm for the least and most variable observerpairs,respectively.AssessingtheagreementbetweenthenodulesizemeasurementsusingTOMOandCTbythedifferencebe-tweentheobservers meandiametermeasurement forthetwomodalitiesresultedinmeanmeasurementerrorsof20.65 mm(95%CI, 20.91 to 20.40) with a 95%LOAof 22.53 to1.22 mm forthe comparison of TOMO and CT. BlandAltmanplotsillustratingtheagreementareprovidedinFigure6.The 95%LOAof the diameter measurements for individualobserversusingTOMOandCTimagesrangedfrom21.16to0.37 mm for the least variable observer to 23.47 to 2.04 mm forthe most variable observer. The 95% LOA for all of the observersand sizes regarding the measurement of the nodule diameter onTOMO and CT are provided in Table 4. BlandAltman plots ofthe agreement between measurements on TOMOand CTimages for the most and least experienced radiologists are showninFigure7.DISCUSSIONWeevaluatedTOMO-derivedparameters, includingnoduledi-ameter, repeatabilityof TOMOobservationsandtheextent ofagreement betweenTOMOdataandthoseacquiredbyCT. Arecent study found that the repeatability values of manualmeasurementsmadebyTOMOandCT werecomparable.7Inthe cited study, clinical nodules that were considered adequatelysegmented were investigated. However, missed nodules onsimpleradiographyareusuallyat theapices, lungbases or incentral locations adjacent tovessels. It is difcult toperformadequate segmentation(not toget confusedby the adjacentstructuresinsideorbesidethelesion)ofsuchnodules.9Several TOMOphantomstudies have reported limited un-derestimationoftheactualsize,whereasstudiesusingCThavefound underestimated or overestimated nodule sizes.7,10,11In thepresentstudy,bothmodalitiesunderestimatedthediametersofphantomnodules. TOMOappearedtoslightlyunderestimatethenodulesize(meanmeasurement error, 20.84 mm); how-ever, suchanerrorisclinicallyrelevant becausenoduleman-agement is based on an absolute nodule size threshold. Inaddition, wefoundthatCT slightlyunderestimatedthenodulesize(meanmeasurementerror, 20.18 mm).The extent of nodule size underestimation by TOMOwassomewhat more marked than that affected by nodule de-lineation.12,13Such artefacts were mostly investigated inTOMOimagesforthebreasts.14,15Although wemeasuredthenodule diametersfromleft to right(thus,notinthedirectionof thescan), darkerareas createdahaloaroundthenodule.This halowas not includedinmanual measurements of thenodule diameter, a factor that affectedthe results. Amorerelevant issue is the possible effect of in-plane artefacts onclinical images. Recently, underestimationof nodulesizeas-sociated with manual measurement of clinical nodules onTOMOhasbeenreported.7Svahnetal16foundthattheextentofin-planeartefactsvariedlinearly with the spherical diameter and relative contrast ofFigure 6. A BlandAltman plot illustrating the agreementbetween two modalities. Dashed line (centre), mean difference[20.65mm (95% confidence interval, 0.91 to 0.40)]. Dashedlines(topandbottom), upperandlowerlimitsofagreement.TOMO, tomosynthesis.Table 4. Mean measurement error at tomosynthesis (TOMO) incomparison with CT by observer and sizeTOMOcompared withCTMeanmeasurementerror (mm)LowerLOA(mm)UpperLOA(mm)Observer1 20.64 21.45 0.172 20.40 21.16 0.373 20.87 22.69 0.964 20.72 23.47 2.04Size(mm)3 0.09 22.46 2.645 20.64 21.63 0.358 21.09 22.07 20.1210 20.98 22.60 0.64LOA, limit of agreement.BJR SSShimet al6 of 8 birpublications.org/bjr Br J Radiol;88:20140040nodules. Their nding that the tendency towards size un-derestimationonTOMOimagesescalatedwithanincreaseinnodulediameterseemstobeconsistentwithourresults. Thecontrast affordedbythe40acquisitionangleof ourTOMOimages may be greater than that of the images produced in thestudybyJohnssonet al17in2010, whousedanacquisitionangleof 30. Thiscontrast might aggravatein-planeartefactsand underestimate the size of larger nodules because thecontrastinTOMOimagesincreasesasacquisitionanglerises.Despite these limitations of TOMO, our present phantomstudy suggested that the measurement values on CTandTOMO were comparable; the mean difference was 20.65 mm.Evenwith larger nodules ($5 mmin diameter), the meandifferencewaslessthan21.1 mm.Regardingrepeatability, the interobserver 95%LOAfor mea-suringTOMOdiametersbythepairofradiologistswhorecor-dedthemostsimilarresultswas20.06to0.83 mm, thevalueswere similar to the CT data. These values were slightly less thanthe variation of 21.3 to 1.5 mm in the measurement of clinicalnodulesreportedbyJohnssonetal7in2012.Theintraobserveragreement was of similar magnitude. It is possible that the evenshape of the phantom nodules was associated with less variationin measurements than in clinical nodules. We found that TOMOdata, including measurement errors, intra- andinterobserveragreement levels and LOAs, improved in proportion to the yearsofexperience.ThisisalsotrueofCT measurements.Ourstudyhadseveral limitations. Onemajordrawbackinthemeasurement study in the phantomnodule was that theobservers could guess the true sizes of the studied objects duringthetwoobservations, resultinginincreasedrepeatability; thus,we sought to make observers completely unaware of the nodulesizeandlocationbypresentingrandomimagestakenusingei-ther imagingmodality. Inaddition, theintrinsiclimitationofTOMO discussed above has affected our results. Optimization ofTOMO technique, including the plane and angle of acquisition,andconstruction ofthephantomnodulerequirefurtherwork.A clinical nodule may vary in shape. Thus, a limitation of TOMOisthatthesizecanbeestimatedonlyinasingleplane, whereasmultidetector CTis three dimensional. However, the thoraciccoronal projection of TOMO is larger than the routine axial imageafforded by CT; therefore, it is possible to measure the superior toinferior nodule diameter on TOMO images more rapidly than ispossible usingCT data. Moreover,theentirethoraxispresentedbyTOMOwithlessradiationandashorterstudytimethanbyCT. Therefore, TOMO should be considered for nodule detectionand follow up for young patients (particularly young women witha risk of breast cancer), and probable benign lesions.CONCLUSIONSOur results suggest that the nodule sizes obtained using TOMOand chest CTare comparable, even for nodules located in areaswhere size measurement is limited on simple radiography,because the size difference was ,1 mm, the LOAs were ofsimilarwidthandtherepeatabilityvaluesweresimilar. How-ever, measurements made by TOMO tended to be smaller thanthose byCT, andthis tendencyampliedas the nodule di-ameterincreased,whichmaybeofconcernifTOMOandCTare to be used interchangeably during nodule follow-up. Theseconcerns maybe alleviatedinthe near future byupgradingTOMOto reduce the number of artefacts encountered inclinicalpractice.Figure7. Theplotsshowthedifferencebetweenthenodulediameter measurement on tomosynthesis (TOMO) and CTagainst theaverageof themeasurements for (a) themostexperienced radiologist and (b) the least experiencedradiologist.Full paper: Pulmonary nodule sizeevaluation withTOMOand CT BJR7 of 8 birpublications.org/bjr Br J Radiol;88:20140040REFERENCES1. BrogdonBG,Kelsey CA,Moseley RDJr.Factorsaffectingperceptionofpulmonarylesions.Radiol ClinNorth Am1983; 21:63354.2. ShahPK,AustinJH,White CS,Patel P,Haramati LB, Pearson GD, et al. Missed non-smallcell lungcancer:radiographicndingsofpotentiallyresectablelesionsevidentonlyinretrospect.Radiology2003; 226:23541.3. Gomi T, Nakajima M, Fujiwara H, Takeda T,Saito K, Umeda T, et al. Comparison betweenchestdigitaltomosynthesisand CT asascreeningmethod todetectarticialpulmonarynodules: aphantom study.BrJRadiol2012; 85:e6229.doi: 10.1259/bjr/126430984. 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