김상윤외 : 서포트벡터머신을이용한영상기반의임상결정보조시스템에근거한전립선암의정낭침습판단 예측하는방법론으로서회귀분석 (logistic regression) 모형이나인공신경망 (artificial neural network, 이하 ANN) 과같은임상결정보조시스템을이용한예측모

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1 대한영상의학회지 2010;63:49-56 서포트벡터머신을이용한영상기반의임상결정보조시스템에근거한전립선암의정낭침습판단 : 1.5T 와 3.0T 전립선자기공명영상에서의임상결정보조시스템의정확성비교 1 김상윤 1,2 이학종 1,3 정대철 4 황성일 1,3 성창규 1,5 조정연 1,2 김승협 1,2 목적 : 서포트벡터머신을이용한영상기반의임상결정보조시스템을만들고, 이를이용하여정낭침습의진단에있어 1.5T와 3.0T 기기간보조시스템의진단정확성을비교하였다. 대상과방법 : 전립선암으로진단받고 1.5T 혹은 3.0T 자기공명영상을시행하고나서전립선절제술을받은 548명환자를대상으로하였다. 1.5T 및 3.0T 기기로검사한집단을각각임의로훈련대상군과테스트대상군으로분류하였다. 영상소견은 2명의영상의학전문의가합의로결정하였다서포트벡터머신을이용하여훈련대상군의정낭의모양, 나이, 전립선특이항원수치를입력값으로, 전립선암의정낭침습가능성을출력값으로하는임상결정보조시스템을만들었다. 이모델을각테스트대상군에적용시켜출력값의정확성을분석하였다. 병리조직학적소견을고려하여, 1.5T와 3.0T에서정낭침습진단에있어민감도, 특이도, 정확도를비교하였다. 결과 : 1.5T 모델의특이도, 정확도는 73.1%, 74.6% 이었고, 3.0T 모델의특이도, 정확도는 90.4%, 88.7% 이었다. 정낭침습진단에있어 3.0T 모델의특이도및정확도가 1.5T 모델보다유의하게높았다 (p < 0.05). 결론 : 전립선암의정낭침습에대해서포트벡터머신을이용하여영상기반의임상결정보조시스템을만들수있었다. 정낭침습진단능의비교에서, 1.5T보다는 3.0T 기기를이용한보조시스템이더높은특이도와정확도를보였다. 전립선암은서양남성에서생기는종양중에서가장흔한종때문이다 (2, 3). 양으로알려져있다. 우리나라의경우, 최근 5년간발병률의실제로전립선특이항원수치 (serum prostate specific 증가속도가빠른종양으로진단과치료에있어그중요성이 antigen: 이하 PSA), 글리슨 (Gleason) 등급, 자기공명영상배가되고있다. 실제로 2003년부터 2005년까지발생한남성소견등을이용하여수술전전립선암의정남침습여부를예암가운데전립선암이차지하는비율은 4.2% 로기타암을제측하기위한여러연구가진행되었다. 특히전립선암환자의외하고위암, 폐암, 간암, 대장-직장암에이어서 5번째로흔한정확한수술전검사로널리시행하는자기공명영상을통한정것으로조사되었고, 인구 10만명당발생률역시 12.7명으로낭침습여부예측에대한여러연구도많이보고되고있다. 하 5번째로높은암으로조사되었다 (1). 지만, 영상을분석하는연구자들간변이폭이크고민감도가전립선암의치료에있어정낭침습여부확인은환자의병기낮은문제가있어현재임상적적용에제한을받는게사실이결정이나예후를결정함에있어중요한항목중하나이다. 수다 (4-10). 술전정낭침범이의심될때는대개수술의적응증이되지못최근여러병원에서도입되어사용되는 3.0T 자기공명영상하고수술을한다하더라도예후가불량한것으로알려져있기기기는 1.5T와비교하여그높은자기장에따른좋아진신호대잡음비 (signal to noise ratio, 이하 SNR) 로상대적으로 1 서울대학교의과대학영상의학과높은공간해상도와측면해상도로환자의진료와진단에있어 2 서울대학교병원영상의학과 3 큰도움을줄것으로기대된다. 무엇보다정낭침습여부판단분당서울대학교병원영상의학과 4 국립암센터영상의학과에높은해상도가필요한만큼이에대한연구적뒷받침이필 5 보라매병원영상의학과요하다고보았다 (11-13). 본연구는 2007년쉐링연구기금의지원으로받아수행된연구임. 이논문은 2010년 1월 18일접수하여 2010년 3월 21일에채택되었음. 최근발표된여러논문에따르면, 다수요소가있는결과를 49

2 김상윤외 : 서포트벡터머신을이용한영상기반의임상결정보조시스템에근거한전립선암의정낭침습판단 예측하는방법론으로서회귀분석 (logistic regression) 모형이나인공신경망 (artificial neural network, 이하 ANN) 과같은임상결정보조시스템을이용한예측모델을만들고, 이를사용한여러연구가있었다 (14-19). 최근에는임상결정보조시스템가운데서포트벡터머신 (support vector machine, 이하 SVM) 을통한접근방법이인공신경회로망의단점을보완한대안으로소개된바있다 (20, 21). 따라서전립선암환자에서 SVM을이용한다면, 전립선암의분포나, 정낭침습여부등패턴을인지하는문제들에있어진일보한해결책을제시할수있을것으로기대된다. 아직전립선암환자에서정낭침습여부를예측하는데 SVM 을이용한연구들은발표된바없고, 전립선자기공명영상에서정낭의모양을입력데이터로이용한병기결정의임상결정보조시스템의정확성에대한분석도현재까지보고된바가없다. 따라서우리는본연구를통해전립선암의정낭침습결과를예측하기위해, 1.5T 자기공명영상과 3.0T 자기공명영상기기를이용한정낭의자기공명영상소견을입력데이터로하여, SVM을이용한영상기반의임상결정보조시스템을만들고, 각기기별로전립선암의정낭침습의진단에있어서임상결정보조시스템의정확성을비교하여보고자하였다. Best, Netherlands) 와 3.0T 자기공명영상기기 (Achieva 3T, Philips Medical Systems, Best, Netherlands) 이었고, 1.5T 기기에는 SENSE FLEX-M 코일, 3T 기기에는 SENSE CARDIAC 코일을이용하였다. 모든환자는바로누운자세에서영상을촬영하였다. 자기공명영상은복부대동맥에서공동요골동맥으로갈리는분기되는시점에서부터치골결합부위까지얻었다. 영상은 T1-강조축상영상, T2-강조축상, 시상, 관상영상을고속스핀에코기술을이용하여얻었다. T2-강조영상에서 TR/TE는 msec/ msec 에에코열길이 (echo train length) 는 8내지 16으로하였다. T1-강조영상에서 TR/TE는 msec/8-12 msec에에코열길이는 4로하였다. 영상영역 (field of view, FOV) 은 15 cm으로하였고, 절편두께 4 mm에절편간간격은 1 mm로하였다. 두명의경험이많은비뇨생식기계영상의학과전문의들이촬영된자기공명영상의후향적분석을담당하였다. 영상분석시분석에영향을줄수있는환자의각종임상정보들은영상의학과의사들에게제공되지않았다. 영상에서정낭의해부학적이상은두영상의학과의사의합의로정등 (6) 이제안한 6 가지의등급을사용하여환자들의정낭모양을 6가지로분류하였다. T2-강조축상영상에서고신호강도를보이는체액을샘 내부에포함하고저신호강도의벽을가진포도모양의형상을 대상과방법 띠는정상정낭의경우를 등급 0 로하고, 해부학적으로는정 상이지만 T2-강조축상영상에서샘내부의신호강도가비정 본연구는기관내연구위원회 (Institutional Research Board, 이하 IRB) 의승인하에본원에서 2006년 1월부터 2007년 12월까지전립선초음파유도하조직검사 (transrectal ultrasound [TRUS] guided prostate biopsy) 로전립선암으로확진받고전립선절제술을시행한 548명의환자를연구대상으로하였다. 대상환자들의평균나이는 65.7 ± 6.7세 ( 범위, 39세부터 79세까지 ) 로수술전자기공명영상을시행한환자들은이전에전립선유도하조직검사를통해전립선암으로확진되었고, 호르몬치료나방사선치료등을받은기왕력이없는환자들을대상으로하였다. 환자들은수술전병기결정을위해무작위추출방법으로 상을보이는경우를 등급 1 로분류하였다. 전립선기저부와맞닿아있는정낭벽일부가두꺼워진소견이보이나, 양쪽정낭이대칭성이유지되는경우를 등급 2 로, 정낭벽전체가두꺼워진소견이보이나, 양쪽정낭의대칭성이유지되는경우를 등급 3 으로분류하였다. 양쪽정낭의대칭성이소실되고, T2-강조영상에서저신호강도를보이는국소병변이보이나, 종양은보이지않는경우를 등급 4 로, 정낭의해부학적구조가소실되었으면서, T2-강조영상에서저신호강도의종양이뚜렷하게보이는경우를 등급 5 로분류하였다 (6). 1979에 Vapnik에의해처음고안된이후, 여러 SVM 모델이사용되었는데 (22), 본연구에서는 SVM 모델가운데 구분하여 1.5T(n= 203) 혹은 3.0T(n= 345) 기기로자기공 Chang과 Lin이 소개한 LIBSVM을 사용하였다 명영상검사를시행받았다. 이후 1.5T 기기와 3.0T 기기를시행한각집단에서각각무작위추출방법으로훈련대상군과테스트대상군으로분류하였다. 훈련대상군은 SVM 모델을만들기위한대상군이고, 테스트대상군은만들어진모델을통해자기공명영상기기간의차이를확인해보기위한대상군이다. 1.5T 시행집단은훈련대상군은 1.5T 집단수의 2/3인 136명으로하였고, 테스트대상군은 1.5T 집단수의 1/3인 67 명으로하였다. 3.0T 시행집단도 3.0T 집단수의 2/3는훈련대상군 230명, 1/3은테스트대상군 115명으로하였다. 환자의나이, 전립선특이항원수치등환자들의임상적데이터도조사하였다. 촬영에사용된자기공명영상장치는 1.5T 자기공명영상기기 (Gyroscan Intera 1.5T, Philips Medical Systems, ( 1.5T나 3.0T 자기공명영상기기를시행한각훈련대상군에서얻은정낭의모양, 환자의나이, 전립선특이항원수치의입력데이터를 SVM 모델에입력한뒤, 각환자당한개의출력값을얻었고, 정낭으로의암전이가있는경우수치 1 을, 없는경우수치 -1 을산출하도록반복테스트를거쳤다. 전립선암의정낭침습가능성을나타낼수있도록 S자형 (sigmoid) 함수를적용하여 SVM 모델의출력값을가능성의백분율로변환하였다 : P(x) = 1/(1 + e-x), (x: 인공신경망출력값 ; P: 전립선암의정낭침습가능성 ). 이러한방식으로훈련대상군의데이터들을이용하여 1.5T와 3.0T 각각의경우에있어서정낭침습의확률을예측할수있는영상기반의임상결정보조시스템을만들었다. 50

3 대한영상의학회지 2010;63:49-56 위에서만든각시스템이전립선암의정낭침습여부를얼마나잘예측하는가를확인하기위해각테스트대상군 (1.5T 67 명 ; 3.0T 115명 ) 에적용시켰다. 각대상군의 3가지입력데이터 ( 정낭의모양, 환자의나이, 전립선특이항원수치 ) 를 SVM 모델에입력한뒤, 출력값을얻어이를수신자판단특성곡선 (receiver operating curve, 이하 ROC) 분석을시행하여가장정확하게구별해낼수있는식별치 (discriminating value) 를구하고, 각모델별민감도, 특이도, 정확도를얻었다. 카이제곱검정 (Chi square test) 을사용하여 1.5T와 3.0T 의민감도, 특이도, 정확도를비교하였다. 수신자판단특성곡선은 MedCalc 통계소프트웨어 (Version , MedCalc Software, Mariakerke, Belgium) 를이용하였다. 통계적으로 p 값이 0.05 미만인경우임상적으로유의한차이가있다고보았다. 결과 Table 1에서보는것처럼, 1.5T 집단 (n=203) 의평균나이는 66.7 ± 6.4세 ( 범위, 48세부터 79세까지 ) 였고, 전립선특이항원수치평균은 11.1 ± 18.2 ng/ml이었다. 3.0T 집단 (n=345) 의평균나이는 65.1 ± 6.8세 ( 범위, 39세부터 79세까지 ) 였고, 전립선특이항원수치평균은 13.7 ± 15.3 ng/ml로, 두집단사이의연령과전립선특이항원수치는통계적인차이를보이지않았다 (t-test, p > 0.05). 1.5T 집단에서는훈련대상군 (n=136) 의평균나이는 66.5 ± 6.6세 ( 범위, 48세부터 79세까지 ) 였고, 전립선특이항원수 치평균은 ± 20.9 ng/ml이었다. 테스트대상군 (n=67) 의평균나이는 67.1 ± 6.0세 ( 범위, 48세부터 78세까지 ) 였고, 전립선특이항원수치평균은 9.28 ± 10.6 ng/ml 로, 두대상군사이의연령과전립선특이항원수치는통계적인차이를보이지않았다 (t-test, p > 0.05). 3.0T 집단에서훈련대상군 (n=230) 의평균나이는 64.9 ± 6.8세 ( 범위, 39세부터 79세까지 ) 였고, 전립선특이항원수치평균은 ± 10.5 ng/ml이었고, 테스트대상군 (n=115) 의평균나이는 65.4 ± 6.7세 ( 범위, 49세부터 80세까지 ), 전립선특이항원수치평균은 ± 15.5 ng/ml 로역시두대상군사이의연령과전립선특이항원수치는통계적차이를보이지않았다 (t-test, p > 0.05). Table 2에서보는것처럼, 자기공명영상에서의정낭의등급에따른병리양성소견빈도와병리결과는다음과같았다. 1.5T 기기로시행한환자의경우, 등급 0의경우훈련대상군과테스트대상군은각각 14.3%(7/49), 12.5%(3/24) 에서정낭침습을보였고, 등급 1의경우각각 12.5%(2/16), 30%(3/10), 등급 2의경우 13.0%(3/23), 9.1%(1/11), 등급 3의경우 18.8%(6/32), 18.8%(3/16), 등급 4의경우 72.7%(8/11), 80.0% (4/5), 등급 5의경우 100% (5/5), 100%(1/1) 의정낭침습율을보였다. 3.0T 기기로시행한환자의경우, 등급 0의경우훈련대상군과테스트대상군은각각 4.5%(7/155), 5.1%(4/79) 의정낭침습율을보였고, 등급 1의경우각각 5.3%(1/19), 10%(1/10), 등급 2의경우 20.0%(2/10), 0.0%(0/4), 등급 3의경우 0.0%(0/28), 6.7%(1/15), 등급 4의경우 66.7%(8/12), 60.0%(3/5), 등급 5의경우 66.7%(4/6), 100%(2/2) 의정낭침습율을보였 Table 1. Mean and Standard Deviations of Input Parameters in the Training and Test Groups Mean ± SD 1.5T Group 3.0T Group Training Group Test Group Total Training Group Test Group Total (n = 136) (n = 67) (n = 203) (n = 230) (n = 115) (n = 345) Age (year) 66.5 ± ± ± ± ± ± 6.8 Total PSA (ng/ml) ± ± ± ± ± ± 15.3 Note. SD= standard deviation, PSA= prostate specific antigen Table 2. MR Findings of Seminal Vesicle and Histopathologic Results The Ratio of SVI at Histopathologic Results MR Class 1.5T Group 3.0T Group Training Group Test Group Training Group Test Group 0 7/49 (14.3%) 3/24 (12.5%) 7/155 (4.5%) 4/79 (5.1%) I 2/16 (12.5%) 3/10 (30.0%) 01/19 (5.3%) 01/10 (10.0%) II 3/23 (13.0%) 1/11 (9.1%)0 002/10 (20.0%) 00/4 (0.0%) III 6/32 (18.8%) 3/16 (18.8%) 00/28 (0.0%) 1/15 (6.7%) IV 8/11 (72.7%) 04/5 (80.0%) 008/12 (66.7%) 003/5 (60.0%) V.5/5 (100%).1/1 (100%) 0004/6 (66.7%) 0.2/2 (100%) Total 31/136 (22.8%)00 15/67 (22.4%)0 22/230 (9.6%)0 11/115 (9.6%)00 Note. SVI= seminal vesicle invasion 51

4 김상윤외 : 서포트벡터머신을이용한영상기반의임상결정보조시스템에근거한전립선암의정낭침습판단 다. Fig. 1은 SVM을이용하여만든 1.5T와 3.0T MR 영상을바탕으로한임상결정보조시스템의 ROC 곡선이다. 그림에서보듯이 1.5T에서의가장효과적인식별치는 28.3이었고 3.0T 임상결정보조시스템에서의식별치는 31.8이었다. Table 3은 ROC 곡선에서구한식별치를기준으로하여, Table 3. The Results of Statistic Analyses Variable Clinical Decision Support Systems p value 1.5T 3.0T (< 0.05) Sensitivity 80.0% 72.7% Specificity 73.1% 90.4% Accuracy 74.6% 88.7% A B Fig. 1. Receiver operating characteristics (ROC) curve of clinical decision support systems using support vector machine (SVM) model at 1.5 T and 3.0T. A. ROC curve of SVM model at 1.5 T machine shows the cut-off value 28.3 with sensitivity of 80.0% and specificity of 73.1%. B. ROC curve of SVM model at 3 T machine shows the cut-off value of 31.8 with sensitivity of 72.7% and specificity of 90.4%. A B Fig. 2. A 76-year-old man with PSA of and high probability of seminal vesicle invasion suggested by 3.0T SVM model. 3.0T prostate MR axial (A) and coronal (B) images show wall destruction of seminal vesicle (arrows). The SVM model suggested that the probability of seminal vesicle invasion in this patient is Regarding that the discriminating value in 3.0T SVM model is 31.8, the probability of seminal vesicle invasion in this patient is very high. The pathologic report revealed that seminal vesicle invasion is present. 52

5 대한영상의학회지 2010;63: T 혹은 3.0T에서테스트대상군의입력데이터를이용하여구한민감도, 특이도, 정확도및통계결과들이다. 1.5T 집단에서 SVM 모델의민감도, 특이도, 정확도는각각 80.0%, 73.1%, 74.6% 이었고, 3.0T 집단에서의 SVM 모델의민감도, 특이도, 정확도는각각 72.7%, 90.4%, 88.7% 이었다. 카이제곱검정결과, 정낭침습의진단에있어서민감도는 1.5T와 3.0T 대상군에서통계적으로유의한차이를보이지않았으나, 3.0T에서통계적으로유의한높은특이도 (p = ) 와정확도 (p = ) 를보였다. Fig. 2, 3은각각 3.0T와 1.5T 자기공명영상을시행했던환자들의영상이다. 3.0T 자기공명영상을시행했던 Fig. 2 환자의경우, SVM 모델에서정낭침습가능성이 61.6으로효과적인식별치인 31.8을고려할때, 정낭침습의가능성이크다고나왔다. 수술후, 병리결과에서전립선암의정낭침습이확인되어영상에입각한임상결정보조시스템의결과가병리결과와일치했던예이다. 1.5T 자기공명영상을시행했던 Fig. 3 환자의경우, SVM 모델에서는정낭침습가능성이 27.6으로효과적인식별치인 28.3을고려할때, 정낭침습의가능성이적다고나왔다. 하지만, 수술후병리결과에서는정낭침습이확인되어영상에입각한임상결정보조시스템의결과가병리결과와다르게나왔던예이다. 고찰전립선암환자의정낭침습확인은환자의병기결정이나예후를결정함에있어중요한항목이다. 실제로수술전정낭침범이의심될때는대개수술의적응증이되지못하고수술을한다하더라도예후가불량한것으로알려져있다. 전립선적출 술후 5년무진행확률을보면전립선내에국한된암인경우 95% 이지만정낭침범이있을때는 37% 로유의하게낮아진다 (2, 3). Koh나 Sala 등의연구를보면, 전립선특이항원수치가높은경우, 글리슨등급이높은경우, 전립선기저부에전립선암이위치한경우, 정낭내구조이상을동반한 T2-강조영상에서의정낭내저신호강도소견등을보일때, 상대적으로정낭침습의가능성이크다고언급한바있다 (4, 5). 자기공명영상검사는전립선암환자에서수술전해부학적정보를함께줄수있다는점에서자기공명영상의정낭소견은정낭침습여부를확인하는데반드시필요한부분이라고하겠다 (4, 6, 23-25). 이전의연구에서자기공명영상기기를통한정낭침습의진단의정확도가85% 정도까지나온바있으나, 민감도와특이도에있어서는각각 50-71%, 66-95% 까지넓은범위로연구마다차이를보였다. 이는영상소견을분석하는연구자들간의변이가컸기때문이다. 정등 (6) 의논문을보면, 정낭의대칭성, 정낭내체액의신호강도이상유무, 정낭벽의이상, 정낭의해부학적이상등의기준에맞추어 6가지로단순화시키는과정을통해주관적인등급보다정확도가높게나왔다. 본연구에서도연구자간의변이에따른차이를최소화하기위해정등 (6) 의논문에따라 6가지로단순화하였고, SVM 모델의입력값에정낭의모양과함께전립선특이항원수치와환자의나이등임상적인데이터를함께입력하도록하였다 (5-11). 정등 (6) 의연구에언급된방법에의해 등급 0 부터 등급 5 까지구분하는방법을통해서 1.5T와 3.0T 각환자군별로병리결과와영상소견의분포를보았을때, 등급 4 와 등급 5 에서병리결과상의정낭침습으로나온환자수가 등급 0, A B Fig. 3. A 77-year-old man with PSA of 15.3 and low probability of seminal vesicle invasion suggested by 1.5T SVM model. 1.5T prostate MR axial (A) and coronal (B) images show no definite abnormality in seminal vesicle. The SVM model suggested that the probability of seminal vesicle invasion in this patient is Regarding that the discriminating value in 1.5T SVM model is 28.3, the probability of seminal vesicle invasion in this patient is low. However, the pathologic report revealed that seminal vesicle invasion is present. 53

6 김상윤외 : 서포트벡터머신을이용한영상기반의임상결정보조시스템에근거한전립선암의정낭침습판단 등급 1, 등급 2, 등급3 보다많았던정등 (6) 의연구결최근임상적으로많이사용되는 3.0T 자기공명영상기기는과와유사하였다. 표 2에서보는것처럼 1.5T 집단의경우, 1.5T와비교하여그높은자기장에따른좋아진신호대잡음 등급 0~3 의소견을보이는환자들의경우, 11.8~18.8% 에비 (SNR) 를보이며, 상대적으로높은공간해상도와측면해서병리적으로정낭침습소견을보였던데반해, 등급 4~5 상도로환자의진료와진단에있어큰도움을줄것으로생각의경우, 75.0~100.0% 에서정낭침습이있는것으로나왔고, 할수있다. SVM 모델을이용하여 1.5T 기기와 3.0T 기기의 3.0T 집단역시 등급 0~3 의소견을보이는환자들의경우, 정낭침습진단의정확도를조사한본연구에서는특이도와정 2.3~14.3% 에서정낭침습소견을보였던데반해, 등급확도가 1.5T에비해 3.0T 기기가통계적으로유의하게높다는 4~5 의경우, 64.7~75.0% 에서정낭침습이있는것으로나결론이나왔다. 왔다. Sosna 등 (12) 의연구에서는직장내코일을사용하는 1.5T 1.5T 집단과 3.0T 집단간에정낭침습비율은다소차이를기기와비교하여위상배열코일을사용하더라도 3.0T 자기공보였다. 1.5T 집단이 22.4~22.8% 의정낭침습소견을보인명영상기기로전립선스캔시유사한질의영상을얻을수있데반해, 3.0T 집단의경우, 9.6% 로다소낮게나왔다. 하지다고하였다. 이러한결과는박등 (11) 의연구에서도언급된만, 각집단내훈련대상군과테스트대상군사이의비율은큰바있다. 특히전립선암이캡슐을넘어서거나정낭침습을보이차이를보이지않았다. 본연구의취지가성공적인영상기본는 pt3의병기에해당하는전립선암의경우, 3.0T 자기공명영의임상결정보조시스템을만들고, 이를이용하여 1.5T와상기기의정확도가 1.5T에비해높다고기술하였다. 3.0T 간의민감도, 특이도, 정확도를비교하고자하였던것이 Torricelli 등 (13) 의연구에따르면, 정낭침습부분에있어기에각집단의영상소견과병리소견간의어떤통계적인분영상의질이직장내코일을사용한 1.5T 기기가체부코일을석은시행하지않았지만, 1.5T와 3.0T 자기공명영상을시행한사용한 3.0T 기기에비해낫다는결론이나왔지만, 이연구의집단의수차이와함께정낭침습의발병률의차이는본연구의경우대상군의수가적다는점에서논란의여지가있다고보았한계점이될가능성이있을것이다 (6). 다. 직장이좁은경우나, 직장, 항문을수술한경우, 얼마전정낭침습과관련하여 SVM이나인공신경망같은임상결정해당부위에방사선치료등을받은경우같이직장내코일을보조시스템을사용한논문은없었다. 이번연구에서사용된사용하는데제한이있는환자에대해서동체표면코일을사임상결정보조시스템인 SVM 모델의경우, Vapnik에의해용하고도임상적으로유용한정도의질좋은전립선부위영상처음고안된이후, 여러연구에서체계적분류나회귀분석을을얻을수있는 3.0T 기기의사용이환자의진료에있어더위한모델로쓰여왔다 (22). SVM은강력한통계적이론에기유용할것으로해석할수있는대목이다. 초하고있어패턴을인식하는문제를해결하거나체계화하는본연구의한계점은 Beyersdorff 등 (31) 의연구에서처럼데한걸음더나아갈수있었다 (26). SVM은훈련데이터에같은환자에게 1.5T와 3.0T를함께시행하여직접비교하지서각각다른결과값을보이는데이터를효율적으로분리하기못하였다는점이다. 이들의연구에서는영상의질과전립선암위하여지도화함수 (non-linear mapping function) 라고하의발견에있어직장내코일을사용한 1.5T가동체코일을사는함수를이용하여데이터의구별성을높게한다 (27, 28). 본용한 3.0T보다우수하다고보았다 (31). 물론작은대상군연구에서는이러한데이터의구별성이높은 SVM의장점을이 (n=24) 을대상으로하였다는점이이연구의제한점이면서도용하여전립선암의정낭침습여부를구분하고자하였다. 두번의자기공명영상을같은환자에게시행하는것이가능했 SVM 모델의장점은내부체계가서포트벡터에만영향을던이유라고연구의말미에스스로밝혔지만, 윤리적인이유와받기때문에, 인공신경망체계의경우처럼전체입력세트에경제적인이유로말미암아본연구의많은환자군을대상으로영향을받지않는다는점이고, 또한커널함수 (kernelfunction) 를이용함으로써많은수의특징들을효과적으로처리할수있다. 는그런직접적인비교를할수없다는점이제한점이라고할수있음으로해서 SVM 모델을이용한결과가최상의인공신본연구의또다른한계점이라고한다면, 앞에서언급한것경망모델의결과만큼이나유용하다는경험적인보고들이나처럼 1.5T(n = 203) 와 3.0T(n = 345) 자기공명영상을시행오고있다 (29, 30). 한환자수의차이가있었다는점이다. 각대상군을직접비교본연구에서, 1.5T와 3.0T 각각에서얻은훈련대상군의정하는것이아니라각대상군을훈련대상군과테스트대상군으낭의소견, 환자의나이, 전립선특이항원수치등의입력값로나누어임상결정보조시스템을만들고이를통해두기기을가지고각자기공명영상기기의영상에입각한영상소견과의임상결정보조시스템의정확도를비교하는연구였지만, 임상결과를바탕으로한임상결정보조시스템을만들수있환자수의차이에따른입력데이터의선택오류가능성을완었다. 이를통해 1.5T와 3.0T 기기가운데어떤기기가좀더전히배제하지못했다는점이한계라고할수있겠다. 정낭침습을진단하는데높은정확도를보이는가를비교할수본연구의또다른한계점은본연구에서는영상정보, 임상있었다. 이러한임상결정보조시스템을이용한다면자칫영정보를포함하는영상기반의임상결정시스템을비교하였기때상판독의개인의소견만으로발생할수도있는오류를줄이문에 3.0T 와 1.5T 자기공명영상기기의직접적인영상화질고, 환자들이나임상의들에게좀더일관성있고유용한도움비교에는제한점이있다고할수있다. 을제공할수있을것으로생각한다. 결론적으로, 본연구에서 SVM을이용하여전립선암의정낭 54

7 대한영상의학회지 2010;63:49-56 침습을예측하는영상소견에입각한임상결정보조시스템을만들수있었고, 1.5T보다는 3.0T 자기공명영상기기를이용한임상결정보조시스템이정낭침습진단에유의하게높은특이도와정확도를보임을확인할수있었다. 이러한영상기반의임상결정보조시스템의개발은임상결과혹은영상결과만으로판단했을때발생할수있는오류를줄이고좀더일관성있고객관적인판단자료를제공함으로써전립선암환자의임상결정에도움이될것으로생각한다. 참고문헌 1. Won YJ, Sung JH, Jung KW, Kong HJ, Park SH, Shin HR, et al. Nationwide cancer incidence in Korea, Cancer Res Treat 2009;41: Kang TJ, Song CR, Song GH, Shin GH, Shin DI, Kim CS, et al. The anatomic distribution and pathological characteristics of prostate cancer: a mapping analysis. Korean J Urol 2006;47: Hull GW, Rabbani F, Abbas F, Wheeler TM, Kattan MW, Scardino PT. Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol 2002;167: Koh H, Kattan MW, Scardino PT, Suyama K, Maru N, Slawin K, et al. A nomogram to predict seminal vesicle invasion by the extent and location of cancer in systematic biopsy results. J Urol 2003;170: Sala E, Akin O, Moskowitz CS, Eisenberg HF, Kuroiwa K, Ishill NM, et al. Endorectal MR imaging in the evaluation of seminal vesicle invasion: diagnostic accuracy and multivariate feature analysis. Radiology 2006;238: Jung DC, Lee HJ, Kim SH, Choe GY, Lee SE. Preoperative MR imaging in the evaluation of seminal vesicle invasion in prostate cancer: pattern analysis of seminal vesicle lesions. J Magn Reson Imaging 2008;28: Ikonen S, Karkkainen P, Kivisaari L, Salo JO, Taari K, Vehmas T, et al. Endorectal magnetic resonance imaging of prostatic cancer: comparison between fat-suppressed T2-weighted fast spin echo and three-dimensional dual-echo, steady-state sequences. Eur Radiol 2001;11: Ikonen S, Karkkainen P, Kivisaari L, Salo JO, Taari K, Vehmas T, et al. Magnetic resonance imaging of clinically localized prostatic cancer. J Urol 1998;159: Rorvik J, Halvorsen OJ, Albrektsen G, Ersland L, Daehlin L, Haukaas S. MRI with an endorectal coil for staging of clinically localized prostate cancer prior to radical prostatectomy. Eur Radiol 1999;9: Schiebler ML, Yankaskas BC, Tempany C, Spritzer CE, Rifkin MD, Pollack HM, et al. MR imaging in adenocarcinoma of the prostate: interobserver variation and efficacy for determining stage C disease. AJR Am J Roentgenol 1992;158: Park BK, Kim BH, Kim CK, Lee HM, Kwon GY. Comparison of phased-array 3.0-T and endorectal 1.5-T magnetic resonance imaging in the evaluation of local staging accuracy for prostate cancer. J Comput Assist Tomogr 2007;31: Sosna J, Pedrosa I, Dewolf WC, Mahallati H, Lenkinski RE, Rofsky NM. MR imaging of the prostate at 3 Tesla: comparison of an external phased-array coil to imaging with an endorectal coil at 1.5 Tesla. Acad Radiol 2004;11: Torricelli P, Cinquantini F, Ligabue G, Bianchi G, Sighinolfi P, Romagnoli R. Comparative evaluation between external phased array coil at 3T and endorectal coil at 1.5T: preliminary results. J Comput Assist Tomogr 2006;30: Suzuki H, Komiya A, Kamiya N, Imamoto T, Kawamura K, Miura J, et al. Development of a nomogram to predict probability of positive initial prostate biopsy among Japanese patients. Urology 2006;67: Snow PB, Smith DS, Catalona WJ. Artificial neural networks in the diagnosis and prognosis of prostate cancer: a pilot study. J Urol 1994;152: Stephan C, Cammann H, Semjonow A, Diamandis EP, Wymenga LF, Lein M, et al. Multicenter evaluation of an artificial neural network to increase the prostate cancer detection rate and reduce unnecessary biopsies. Clin Chem 2002;48: Walz J, Graefen M, Chun FK, Erbersdobler A, Haese A, Steuber T, et al. High incidence of prostate cancer detected by saturation biopsy after previous negative biopsy series. Eur Urol 2006;50: Nam RK, Toi A, Klotz LH, Trachtenberg J, Jewett MA, Appu S, et al. Assessing individual risk for prostate cancer. J Clin Oncol 2007;25: Bianco FJ Jr. Nomograms and medicine. Eur Urol 2006;50: Cortes C, Vapnik V. Support-vector networks. Machine Learning 1995;20: Vapnik V. The nature of statistical learning theory. Berlin: Springer, 2000: Comak E, Arslan A, Turkoglu I. A decision support system based on support vector machines for diagnosis of the heart valve diseases. Comput Biol Med 2007;37: Blute ML, Bergstralh EJ, Iocca A, Scherer B, Zincke H. Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy. J Urol 2001;165: Epstein JI, Partin AW, Potter SR, Walsh PC. Adenocarcinoma of the prostate invading the seminal vesicle: prognostic stratification based on pathologic parameters. Urology 2000;56: Salomon L, Anastasiadis AG, Johnson CW, McKiernan JM, Goluboff ET, Abbou CC, et al. Seminal vesicle involvement after radical prostatectomy: predicting risk factors for progression. Urology 2003;62: Vapnik V. Statistical learning theory, wiley series on adaptive and learning systems for signal processing, communications and control. 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8 김상윤외 : 서포트벡터머신을이용한영상기반의임상결정보조시스템에근거한전립선암의정낭침습판단 J Korean Soc Radiol 2010;63:49-56 Comparison of Accuracies for Image-based 1.5T and 3T MRI Using a Clinical Decision Support System Driven by a Support Vector Machine to Detect Seminal Vesicle Invasion of Prostate Cancer 1 Sang Youn Kim, M.D. 1, 2, Hak Jong Lee, M.D. 1, 3, Dae Chul Jung, M.D. 4, Sung Il Hwang, M.D. 1, 3, Chang Kyu Sung, M.D. 1, 5, Jeong Yeon Cho, M.D. 1, 2, Seung Hyup Kim, M.D. 1, 2 1 Department of Radiology, Seoul National University College of Medicine 2 Department of Radiology, Seoul National University Hospital 3 Department of Radiology, Seoul National University Bundang Hospital 4 Department of Radiology, Research Institute and Hospital, National Cancer Center 5 Department of Radiology, Seoul National University Boramae Hospital Purpose: The purpose of this study is to develop image-based clinical decision support systems (CDSSs) using support vector machine models (SVMs) for the detection of seminal vesicle invasion (SVI) of prostate cancer and to compare the accuracies of 1.5T and 3.0T MR CDSSs. Materials and Methods: A total of 548 prostate cancer patients who underwent a prostatectomy and preoperative MR using 1.5T or 3.0T were enrolled in this study. Each 1.5T and 3.0T group was subdivided into the training group and test group, arbitrarily. Images were analyzed in consensus by two radiologists. CDSS was constructed with input data that has the appearance of a seminal vesicle, PSA level and age in each training group, and with the output data of the probability for SVI using SVMs. The accuracy of the output data were evaluated with data of each test group. After a histopathologic correlation, the sensitivity, specificity and accuracy for the detection of SVI were compared in both 1.5T and 3.0T. Results: For the diagnosis of SVI, the specificity and the accuracy of the 3.0T model were all statistically superior to those of the 1.5T model (90.4% vs. 73.1%; 88.7% vs. 74.6%) (p<0.05). Conclusion: The image-based CDSS for the detection of SVI was successfully constructed using SVM. According to our CDSSs, the specificity and accuracy of 3.0T were superior to those of 1.5T. Index words : Decision Support Systems, Clinical Medical Order Entry Systems Magnetic Resonance Imaging Prostatic Neoplasms Seminal Vesicles Address reprint requests to : Hak Jong Lee, M.D., Ph.D., Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, 300, Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi-do , Korea. Tel Fax hakjlee@snu.ac.kr 56

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