Volume 14, No. 2, December 2010 목차 CONTENTS 원저자화율차이로인해왜곡된영상으로부터금속바늘의위치결정김은주 김대홍 87 ORIGINAL CONTRIBUTIONS Determining the Location of Metallic Needle

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2 Volume 14, No. 2, December 2010 목차 CONTENTS 원저자화율차이로인해왜곡된영상으로부터금속바늘의위치결정김은주 김대홍 87 ORIGINAL CONTRIBUTIONS Determining the Location of Metallic Needle from MR Images Distorted by Susceptibility Difference 87 EJ Kim, DH Kim 삼중음성유방암의자기공명영상소견 : 비삼중음성유방암과의비교최재정 김성헌 차은숙 강봉주 이지혜 95 MRI Findings of Triple Negative Breast Cancer: A Comparison with Non-Triple Negative Breast Cancer 95 이소연 정승희 임현우 송병주 JJ Choi, SH Kim, ES Cha, BJ Kang, JH Lee, SY Lee, SH Jeong, HW Yim, BJ Song 정상노인및경도인지장애및알츠하이머성 103 치매환자에서의한국인뇌구조영상표준판개발김민지 장건호 이학영 김선미 류창우신원철 이수열 Development of a Korean Standard Structural Brain Template in Cognitive Normals and Patients with Mild Cognitive Impairment and Alzheimer s Disease MJ Kim, GH Jahng, HY Lee, SM Kim, CW Ryu, WC Shin, SY Lee 103 활성자극파라다임 fmri에서저주파요동성분분석나성민 박현정 장용민 115 Low Frequency Fluctuation Component 115 Analysis in Active Stimulation fmri Paradigm SM Na, HJ Park, YM Chang 유방암환자에서추가병변평가를위한 3 테슬러유방자기공명영상의임상적경험이지혜 김성헌 강봉주 최재정 이아원 121 Clinical Experience of 3T Breast MRI in Detecting the Additional Lesions in Breast Cancer Patients 121 JH Lee, SH Kim, BJ Kang, JJ Choi, AW Lee 뇌피질이형성증의 3차원뇌표면연출영상황승배 곽효성 이상용 진공용 126 Three-Dimensional Brain Surface Rendering Imaging of Cortical Dysplasia 126 한영민 정경호 SB Hwang, HS Kwak, SY Lee, GY Jin, YM Han, GH Chung

3 증례보고뼈주위지방종의자기공명영상소견 : 증례보고배형주 홍석주 김예림 강은영 김학준류영준 정원용 134 CASE REPORTS MR Imaging Findings of Parosteal Lipoma: Case Report HJ Bae, SJ Hong, YL Kim, EY Kang, HJ Kim, YJ Ryu, WY Jung 134 췌장중복낭의자기공명영상소견과수소자기공명분광법 : 증례보고박성희 김미영 서창해 이건영최석진 조재영 139 MR Images and 1 H MR Spectroscopy of Enteric Duplication Cyst of the Pancreas in an Adult SH Park, MY Kim, CH Suh, KY Lee, SJ Choi, JY Cho 세남아에서발생한췌장의비기능성악성신경내분비종양 : 증례보고임세웅 이영환 최시성 조현선 145 Non-Functioning, Malignant Pancreatic Neuroendocrine Tumor in a 16-Year-old Boy: A Case Report SW Lim, YH Lee, SS Choi, HS Cho 145 일차성간림프종 : 자기공명영상과병리소견의연관김한나 신유리 나성은 정은선 오순남최준일 정승은 이영준 151 Primary Hepatic Lymphoma: MR Imaging and Pathologic Correlation HN Kim, YR Shin, SE Rha, ES Jung, SN Oh, JI Choi, SE Jung, YJ Lee 151 논문외 대한자기공명의과학회지제14권색인 156 대한자기공명의과학회회원카드 159 대한자기공명의과학회회원가입안내 160 대한자기공명의과학회입회원서 161 대한자기공명의과학회지윤리규정및투고규정 162 저작권이양에관한동의서 167

4 Determining the Location of Metallic Needle from MR Images Distorted by Susceptibility Difference Eunju Kim 1, Daehong Kim 2 Purpose : To calculate the appearance of the image distortion from metallic artifacts and to determine the location of a metallic needle from a distorted MR image. Materials and Methods : To examine metal artifacts, an infinite metal cylinder in a strong magnetic field are assumed. The cylinder s axis leaned toward the magnetic field along some arbitrary angle. The Laplace equation for this situation was solved to investigate the magnetic field distortion, and the simulation was performed to evaluation the image artifact caused by both readout and slice-selection gradient field. Using the result of the calculation, the exact locations of the metal cylinder were calculated from acquired images. Results : The distances between the center and the folded point are measured from images and calculated. Percentage errors between the measured and calculated distance were less than 5%, except for one case. Conclusion : The simulation was successfully performed when the metal cylinder was skewed at an arbitrary tilted angle relative to the main magnetic field. This method will make it possible to monitor and guide both biopsy and surgery with real time MRI. Index words : Magnetic resonance imaging (MRI) Metallic artifacts Simulations of image distortion Introduction Various metallic devices have been used for implantations or percutaneous procedures, but these metallic implants cause severe magnetic resonance imaging (MRI) image distortions called susceptibility artifacts. Metal-induced artifacts arise from the susceptibility difference between the body tissue and the metal, and the artifacts can be strong enough to deteriorate the whole image (1, 2). A number of methods have been introduced to overcome metallic artifact image distortions. The view angle tilting (VAT) method suggested by Cho et al. is one of the most promising methods to correct the artifact and proved to be useful in medical practice (3, 4). However, the JKSMRM 14:87-94(2010) 1 Fusion Technology Medical Device Team, Korea Food & Drug Administration 2 Molecular Imaging and Therapy Branch, National Cancer Center Received; October 4, 2010, revised; December 14, 2010, accepted; December 15, 2010 Corresponding author : Daehong Kim, Ph.D., Molecular Imaging and Therapy Branch, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si Gyeonggi-do , Korea. Tel Fax dkim@ncc.re.kr - 87-

5 Eunju Kim et al images obtained by the VAT method are convolved with a square function, which is related to sliceselection gradient, so they are blurred. Recently, in order to compensate this image blurring, the additional z-phase encoding technique called as SEMAC(Slice Encoding for Metal Artifact Correction) was reported (5). When imaging patients with metallic devices, such as implants or biopsy needles, image degradation and geometric mis-registration must be solved (3, 6, 8, 9). In particular, it is important to know the exact location of the metallic needle for image-guided biopsy. A few investigators have successfully calculated the amount of shift caused by metallic artifacts (1, 7). Ludeke et al. (1) calculated the shift when the metal cylinder was perpendicular to the main magnetic field (1). Ladd et al. (7) studied the case where the metal cylinder is at an arbitrary angle with respect to the magnetic field, but they did not consider the slice distortion caused by the slice-selection gradient. If the slice-selection gradient is not taken into account with the readout gradient, then the calculated artifact is different from the real artifact. To explore the metal artifact, we assumed an infinite, non-magnetic metallic cylinder in a strong magnetic field. The cylinder s axis leaned toward the main magnetic field along some arbitrary angle. We solved the Laplace equation for these situations to investigate the magnetic field distortion (7), and then we successively simulated the effect of the readout gradient and slice gradient magnetic field. As a result, the artifact s shape and size were generated, and the location of the cylinder s center was calculated and determined. We compared the results of the calculated images with the real images. The real images were acquired on a 1.5 T clinical MRI system (GE HORIZON). The phantom was made of a stainless steel rod immersed in a bottle containing doped water. The goal of our new method is to exactly calculate the location of the cylinder s center, not to reduce or remove the artifact, so this method can be applied during surgery with a real-time open magnet MRI system for successfully guiding needles. Materials and Methods Calculation of Field Distortion Ladd et al. calculated the field distortion caused by an infinite cylinder that leans along a strong, homogeneous magnetic field, B 0, which is illustrated in Fig. 1, where the permeability inside and outside the cylinder are μ i and μ e, respectively, and the radius of the cylinder is R. For convenience, the axis of cylinder is parallel to y-axis, and the tilt angle between the magnetic field and the plane perpendicular to the cylinder s axis is θ. The external magnetic field can be expressed as B 0 = y^b 0 sin θ+z^b 0 cos θ, [1] where x^, y^, z^, are unit vectors for each direction. The resulting fields are B μ e -μ i μ e -μ i i = z^b 0 cos θ 1- +y^b 0 sin θ1- μ e +μ i μ e μ i Fig. 1. An infinite metallic cylinder is put in a strong homogeneous magnetic field. The angle between the main magnetic field and the plane perpendicular to the metal cylinder is θ. The right hand coordinate system is used. The axis of the cylinder is parallel to y-axis and the main magnetic field Bo lies in y-z plane. B μ z 2 - x 2 e -μ i e = z^b 0 cos θ 1- R μ 2 (z 2 +x 2 ) 2 e +μ i μ e -μ i 2xz - x^b 0 cos θ R 2 y^b 0 sin θ, [2] μ (z 2 +x 2 ) 2 e +μ i where B i and B e denote the magnetic field inside and outside cylinder, respectively. The relative permeability μcan be written as a - 88-

6 Determining the Location of Metallic Needle from MR Images Distorted by Susceptibility Difference function of susceptibility χ, as follows: μ=1+χ. For MRI χ 1, so we can approximate μ e -μ i χ =, [3] μ e +μ i 2 χ=χ e -χ i Computer Simulations of the Distortion Distortions were simulated using Mathematica (Wolfram Research, version 3.0). When a slice-selection gradient is applied, the slice s shape is distorted by the susceptibility difference, so we simulated a distorted shape caused by the slice selection gradient and by the superposition of distortions caused by the readout gradient. First, for the effect of slice gradient, we assumed that an infinitely thin slice was selected by the slice selection gradient: G ss =-z^g ss sin θ+y^g ss cos θ, [4] whose direction was perpendicular to the main magnetic field. A frequency = (B 0 +yg ss ) to select the slice at y=z tan θresults in an actual slice at r(x, y, z) defined by Using Eq. [2], Eq. [4] and Eq. [5], the selected slice at exterior of the cylinder is given as χ B 0 z 2 - x 2 y=z tan θ+ R 2. [6] 2 (z 2 +x 2 ) 2 G ss Because we are not concerned with the inner metal, no calculation is needed for the interior of the cylinder. Using Mathematic, this situation is plotted in Fig. 2a. Next, for the distorted slice we applied a readout gradient. In the readout gradient, the points move along the direction of the readout gradient which is assumed to be applied in the same direction of B0, that is, G r = z^g r cos θ+y^g r sin θ. [7] We also calculated this shift in a similar way we used in the case of a slice-selection gradient. The pixel r will be displayed at position r -. r=r - χ B 0 z 2 - x 2 -r =-cos θ R 2 [8] 2 (z 2 +x 2 ) 2 From Eq. [8], we can calculate the shift for each direction, as follows: χ B 0 z 2 - x 2 z=-cos 2 θ R 2, 2 (z 2 +x 2 ) 2 G r G r B e +(xx^+yy^+zz^) G ss=b 0 +(z tan θy^+zz^) G ss. [5] Fig. 2. Simulated slices were plotted with Mathematica. The tilted angle of the metal cylinder is 30. (a). The distorted slice is selected by the slice selection gradient. The direction of the slice gradient is perpendicular to main magnetic field. (b). When the readout gradient is applied to the slice in (a), each pixel in the slice is shifted along the readout gradient direction. The direction of the readout gradient is parallel to the main magnetic field. (c). The top view of (b) is plotted where the point f represents the folded point and p represents the piled point

7 Eunju Kim et al χ z 2 - x 2 y=-cos θsin θ R 2. [9] 2 (z 2 +x 2 ) 2 Each of the points on the surface of Eq. [6] will be shifted by the readout gradient calculated with Eq. [9]. As a result of Eq. [6] and Eq. [9], the components of the distorted surface are expressed as χ z-component: Z=z-cos 2 θ 2 G r R 2 x-component: X=x χ B 0 y-component: Y=z tan θ+ 2 R 2 χ z 2 - x 2 - cos θsin θ R 2 [10] 2 (z 2 +x 2 ) 2 The simulated image in Fig. 2 is relatively similar to the real image generated from MR scanner. There were regions of condensed lines that appeared as bright as regions on the real image. To understand the shape of the susceptibility artifact, we watched the brightest points. As shown in Fig. 2c, the brightness is caused when a slice is folded at one point (i.e., the folded point, f ) or when the slice is piled up around a point (i.e., the piled point, p ). The tangent line at the folded point is parallel to the direction of slice selection gradient, so the folded point can be calculated by simple differentiation. Initially, due to symmetry, the folded point will be on the z-axis, so all x s in Eq. [10] can be set to zero. Then, we find the point where the incline of the tangent line is -1/tan θ, as follows: dy 1 1 dy dz B 0 G r B 0 G ss B 0 G r z 2 - x 2 (z 2 +x 2 ) 2 z 2 - x 2 (z 2 +x 2 ) 2 dz tan θ+ cos θsin θ - G r G ss χb 0 R 2 z -3 = = dz 1 dz 1+cos 2 θ G χb 0 R 2 z -3 r In the case of x 2 =z 2 in Eq. [10], the shift by susceptibility artifact does not occur and those points of x 2 =z 2 in Eq. [10] stay stationary under the susceptibility artifact. So, other points around those stationary points are shift and piled up at those stationary points. So, the piled point will lie on the plans in Eq. [13]. x=z, x=-z, y=z tan θ [13] Since Eq. [12] relates to the folded point, we can plot the distance from the cylinder s center to the folded point as a function of the metallic cylinder s tilt angle relative to the main magnetic field (Fig. 3). Piled points are located on the matching lines of all plans in Eq. [13]. By using these points, we can calculate the exact location of the cylinder s center in the image without any complementary devices. The simulated images in Fig. 4 show the slice shape caused the by the magnetic field distortion, which varied as a function of tilt angle (0, 15, 30, 45, 60, and 75 ). We confirmed that there were large changes in artifact size that were caused by varying the tilt angle. This result corresponded to that shown in Fig. 3. All of these findings indicate that image distortion is not proportional to tilt angle. As θapproached 90, the artifact decreased in size and eventually disappeared. Phantom and Image A stainless-steel cylindrical rod was chosen for the phantom imaging. The stainless steel rod was inserted in a water container doped with CuCl 2. The rod s susceptibility was not available because the rod s constituents were not published, so the rod s susceptibility was calculated from the image (θ=0) using Eq. [12] and Eq. [13] as χ= The 1 = -. [11] tan θ The result is tan θ 1 z 3 = χb 0 R 2 - cos 2 θ. G ss The distance from the zero-point to the folded point is tan θ 1 1 r 3 = χb 0 R 2 -. [12] cos θ G ss G r G r Fig. 3. The distance from the cylinder center to the folded point as a function of the metallic cylinder s tilt angle relative to the main magnetic field. X-axis is plotted versus radians. The distance was not proportional to the tilt angle

8 Determining the Location of Metallic Needle from MR Images Distorted by Susceptibility Difference length and diameter of the cylindrical rod were 20 cm and 1 mm, respectively. The phantom images were acquired with a conventional spin echo pulse sequence on a 1.5 T MRI system (General Electric Medical Systems, Milwaukee, WI). The matrix size was , and the field of view (FOV) was 16 cm. Bandwidth was +/-16 khz. Slice thickness was 1 mm. Repetition time (TR) and echo time (TE) were msec and 20.0 msec, respectively. The actual strength of the readout and slice gradients were gauss/cm and gauss/cm, respectively. The tilt angles of stainless still rod to main magnetic field were tried as 0, 8, 24, 32, 44, 56 for MR image. Comparison of Simulated and Acquired Images Using the piled points and folded point, the center of metallic cylinder was determined from MR images. Also, the distance between the center and the folded point was measured. The measured distances were compared to the calculated value from Eq. [12]. Firstly, the piled point were identified on the image as one of the brightest points, and then a straight line were drawn using x=z or x=-z in Eq. [13], which will connect the piled point with the center of the metal cylinder. Secondly, we identified the folded point, which is the other brightest point, and then the vertical line was drawn which connected the folded point and the center of metal cylinder. Finally, the overlapped point of two lines is the center of the metal cylinder. We measured the number of pixels from the center to the folded point, and we could measure the distance from the center to the folded point from images. Using Eq. [12], we could calculate the distance from the center to the folded point for each tilt angle and compared these values to the measured image values. Results We have a sound understanding of the artifact s shape from the simulated metallic artifact. The simulated images with various tilt angles in Fig. 4 coincide with the real images from MR scanner in Fig. 5. In the direction of read-out gradient, one can observed little changes with the distance between the brightest points in Fig. 4 and Fig. 5. On the other hand, in the direction of phase gradient the ranges of artifact decrease Fig. 4. Simulated slices are plotted for various tilt angles ((a)-(f)): 0, 15, 30, 45, 60, and 75. The shape of the magnetic field distortion varied as a function of tilt angle. Each slice was generated with the same parameters, except for the tilt angle

9 Eunju Kim et al Table 1. Calculated and Measured Distances from the Cylinder s Center to the Folded Point Tilt Angle(degree) Distance from calculation(cm) Distance from measurement(cm) Error(%) error = { measure - calculate /measure} 100 Fig. 5. Cross sectional images of the stainless steel cylindrical rod were acquired. Its diameter and length were 1 mm and 20 cm, respectively. The tilt angles ( ) measured during imaging were 0, 8, 24, 32, 44, 56, and 73 ((a)-(g)), respectively. The readout gradient direction was top-to-bottom. The artifact shapes did not increase in size along the readout encoding direction, which is similar to the results shown in Fig. 4. according to the tilt angle. As mentioned above, the location of the center can be determined with real image. The distance from the center to the folded point can be also measured from the real image. The distances measured from images were compared to the calculated value using Eq. [12] and those distances were in good agreement, as shown in Table 1. The calculated distances of Table 1 show that the distance does not make a big change according to the tilt angle. These results can be observed in Fig. 3 and both simulated and real images. Percentage errors in Table 1 were less than 5%, except for one case. Errors can occur because it is difficult to precisely select the folded and piled points. For a pixel size of cm, considerable error may result from mispositioning by one or two pixels. Despite this challenge, these results are in good agreement for simulated and acquired images. Discussion The shape of the metallic artifact was determined with simulation under the assumption that the cylinder was infinite in length and skewed in an arbitrary tilted angle relative to the main magnetic field. Artifact shape can be calculated with the method we presented here. Our method is applicable for a stainless steel cylinder as well as other less susceptible materials (e.g., aluminum or titanium). The calculated and measured distances were similar, but there was some percentage of error in the measurement: %. One reasonable explanation is that we did not perfectly mark the folded point and piled point on the images; mismarking by a few pixels can cause considerable - 92-

10 Determining the Location of Metallic Needle from MR Images Distorted by Susceptibility Difference errors. In practice, marking the folded point is easier than marking the piled point; then, using Eq. [12], a user can find the metal cylinder s location. Additionally, if we know the magnetic susceptibility of the implanted metal and the cylinder s tilt angle, we can calculate the radius of the implanted cylinder from Eq. [12]. Precisely knowing the cylinder s location is useful in medical practice. Artifact shape and the location of metal cylinder implanted to human body can be determined, if the metallic cylinder is assumed to be infinite. Magnetic field distortion cannot be calculated at the sharp end of metallic biopsy needles (8-10) because an exact solution of the Laplace equation at the needle s point has not been found (8-10). Recently, artifacts caused by arbitrarily-shaped metallic implants were simulated with numerical methods and complex computer simulation (11). However, there is no method for measuring the location of metallic implants using only images, so further research is needed to be able to measure the location and shape of metallic implants Acknowledgments This research was supported by the Pioneer Research Center Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology ( ). References 1.Lü deke KM, Röschmann P, Tischler R. Susceptibility artefacts in NMR imaging. Magn Reson Imaging 1985;3: Schenck JF. The role of magnetic susceptibility in magnetic resonance imaging: MRI magnetic compatibility of the first and second kinds. Med Phys 1996;23: Butts K, Pauly JM, Daniel BL, Kee S, Norbash AM. Management of biopsy needle artifacts: techniques for RFrefocused MRI. J Magn Reson Imaging 1999;9: Cho ZH, Kim DJ, Kim YK. Total inhomogeneity correction including chemical shifts and susceptibility by view angle tilting. Med Phys 1988;15: Lu W, Pauly KB, Gold GE, Pauly JM, Hargreaves BA. SEMAC: Slice Encoding for Metal Artifact Correction in MRI. Magn Reson Med 2009;62: Arbogast-Ravier S, Gangi A, Choquet P, Brunot B, Constantinesco A. An in Vitro Study at Low Field for MR Guidance of a Biopsy Needle. Magn Reson Imaging 1995;13: Ladd ME, Erhart P, Debatin JF, Romanowski BJ, Boesiger P, McKinnon GC. Biopsy needle susceptibility artifacts. Magn Reson Med 1996;36: Lufkin R, Teresi L, Hanafee W. New Needle for MR-Guided Aspiration Cytology of the Head and Neck. AJR Am J Roentgenol 1987;149: Lufkin R, Teresi L, Chiu L, Hanafee W. A Technique for MR- Guided Needle Placement. AJR Am J Roentgenol 1988;151: Liu H, Martin AJ, Truwit CL. Interventional MRI at High- Field (1.5 T): Needle Artifacts. J Magn Reson Imaging 1998; 8: Balac S, Caloz G, Cathelineau G, Chauvel B, de Certaines JD. Integral method for Numerical Simulation of MRI Artifact Induced by Metallic Implants. Magn Reson Med 2001;45:

11 Eunju Kim et al 대한자기공명의과학회지 14:87-94(2010) 자화율차이로인해왜곡된영상으로부터금속바늘의위치결정 1 식품의약품안전청융합기기팀 2 국립암센터분자영상치료연구과 김은주 1 김대홍 2 목적 : 금속에의한영상왜곡에대한정확한계산하고영상으로부터의금속물질의위치결정한다. 대상및방법 : 주자기장과일정각도를이루는무한히긴비자성금속실린더에대한라플라스방정식을풀고, 이결과를이용하여절편선택경사자계와주파수부호화경사자계에의한영상에왜곡을계산한다. 계산결과를바탕으로하여왜곡된영상으로부터원통형보철물의위치를계산한다. 결과 : Folded point와금속실린더의중심사이의거리를영상으로부터측정하여계산결과와비교한다. 측정결과와계산결과간의퍼센트오차는한경우를제외하고 5% 이내였다. 결론 : 금속실린더가자기장하에있을때, 영상의왜곡을시뮬레이션하였고, 이기술은생검술또는외과수술등을자기공명영상법을이용여실시간모니터링하는데적용할수있을것으로기대한다. 통신저자 : 김대홍, ( ) 경기도고양시일산동구일산로 323, 국립암센터분자영상치료연구과 Tel Fax dkim@ncc.re.kr - 94-

12 MRI Findings of Triple Negative Breast Cancer: A Comparison with Non-Triple Negative Breast Cancer Jae Jeong Choi 1, Sung Hun Kim 1, Eun Suk Cha 1, Bong Joo Kang 1, Ji Hye Lee 1, So-Yeon Lee 1, Seung Hee Jeong 2, Hyeon Woo Yim 2, Byung Joo Song 3 Purpose : To evaluate the magnetic resonance imaging (MRI) and clinicopathological features of triple negative breast cancer, and compare them with those of non-triple negative breast cancer. Materials and Methods : This study included 231 pathologically confirmed breast cancers from January 2007 to May We retrospectively reviewed the MRI findings according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon: mass or non-mass type, mass shape, mass margin, non-mass distribution, and enhancement pattern. Histologic type, histologic grade, and the results for epidermal growth factor receptor, p53, and Ki 67 were reviewed. Results : Of 231 patients, 43(18.6%) were triple negative breast cancer. Forty triple negative breast cancers (93.0%) were mass-type lesion on MRI. A round or oval or lobular shape (p=0.006) and rim enhancement (p=0.004) were significantly more in triple negative breast cancer than non- triple negative breast cancer. In contrast, irregular shape (p=0.006) and spiculated margins (p=0.032) were significantly more in non-triple negative breast cancer. Old age (p=0.019), high histologic grade (p<0.0001), EGFR positivity (p<0.0001), p53 overexpression (p=0.038), and Ki 67 expression (<0.0001) were significantly associated with the triple negative breast cancer. Conclusion : MRI finding may be helpful for differentiation between triple negative and non-triple negative breast cancer. Index words : Breast cancer Estrogen receptor Progesterone receptor HER2 Magnetic resonance imaging (MRI) JKSMRM 14:95-102(2010) 1 Department of Radiology, College of Medicine, The Catholic University of Korea 2 Clinical Research Coordinating Center, College of Medicine, The Catholic Medical Center 3 Department of Surgery, College of Medicine, The Catholic University of Korea Received; September 27, 2010, revised; November 17, 2010, accepted; December 1, 2010 Corresponding author : Sung Hun Kim, M.D., Department of Radiology, College of Medicine, Seoul St. Mary s Hospital, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul , Korea. Tel Fax rad-ksh@catholic.ac.kr - 95-

13 Jae Jeong Choi et al Introduction Triple negative (TN) breast cancer is a subtype that is negative for the three main receptors for breast cancer, namely estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2). TN breast cancer has been considered to have a clinical feature with aggressive behavior and poor prognosis because there is no specific therapeutic target for the tumor. Previous literatures reported that TN breast cancer had a pathologic entity with a high histologic grade, and an overexpression of molecular factors such as epidermal growth factor receptor (EGFR), and Ki 67 (1-4). However, there are a few reports describing MR imaging features of TN breast cancer (5, 6). We hypothesized that comparison of MRI features between TN breast cancer and non-tn breast cancer could yield additional information for pretreatment planning and assessment of prognosis. Therefore, the purpose of our study was to evaluate the MRI findings of TN breast cancer and to compare the findings with those of non- TN breast cancer. We also compared the MRI findings with the clinicopathological results. Materials and Methods Patients This study consisted of 302 consecutive patients who were confirmed to have breast cancer and who underwent breast MRI in our institution from January of 2007 to May of Seventy one patients were excluded from the analysis for the following reasons; 42 patients underwent MRI after the excision of breast cancer, 24 patients received neo-adjuvant chemotherapy, two patients had cancers that were not visible on MRI scans, one patient had recurrent breast cancer after surgery, one patient had breast sarcoma and one patient had no information available on the ER status of the breast cancer. Two hundred-thirty one breast cancers in 231 patients were enrolled in this study. In patients with two or more pathologicallyconfirmed tumors, including three patients with bilateral breast cancers, the largest one was selected. Total 43 TN breast cancers and 188 non-tn breast cancers were included in this study. The age of the patients ranged from 31 to 86 years (mean age, 53.2 years). The size of the breast cancer ranged from 0.3 to 11.0 cm (mean size, 2.76 cm). This study was approved by the institutional review board of our institution. Imaging Acquisition MR images were acquired with a 1.5T scanner (Signa; GE Medical Systems, Milwaukee, WI, U.S.A. and Achieva; Philips Medical system, Best, the Netherlands) using a breast coil. MRI with the Signa scanner was performed using the following sequences; sagittal, fat-suppressed, fast spin-echo T2-weighted imaging, and axial or sagittal, fat-suppressed, fat-spoiled gradient-echo T1-weighted imaging (TR/TE=6.2/3.1, flip angle of 10, 2.6 mm section thickness, and an acquisition time of 1 min 31 minutes) obtained before and 91, 182, 273, 364 and 455 sec after the rapid bolus injection of 0.2 mmol/kg body weight of Gd-DPTA (Magnevist, Schering, Berlin, Germany). MRI with the Achieva scanner was performed using the following sequences; sagittal, fat-suppressed, fast spin-echo T2- weighted imaging and axial fat-suppressed, fat-spoiled gradient-echo T1-weighted imaging obtained before and 91, 182, 273, 364 and 455 sec after the rapid bolus injection of the same contrast agent. Interpretations of MR Image Findings MRI findings for TN breast cancers and non-tn breast cancers were reviewed by the consensus of two radiologists (with 4 and 9 years of breast MR imaging experience). The morphology and enhancement of the lesions were described according to the BI-RADS lexicon. The lesions were divided into mass or nonmass types. Mass type lesions were assessed for size, shape, margins, and enhancement pattern. Non-mass type lesions were assessed for distribution and enhancement pattern. We evaluated the enhancement pattern on 2 min post-contrast MR images. Pathological Analysis We reviewed the size, histologic type, and histologic grade of the TN and non-tn breast cancers. Immunohistochemistry was performed to assess the expression of the following molecular markers; ER, PR, HER2, p53, Ki 67, and epidermal growth factor receptor (EGFR). ER and PR positivity was defined as the presence of 10% or more positively stained nuclei - 96-

14 MRI Findings of Triple Negative Breast Cancer in ten high-power fields. The intensity of HER2 membrane staining was scored as 0, 1+, 2+ or 3+. Tumors with 2+ or 3+ scores were classified as positive for HER2 overexpression, whereas tumors with scores of 0 or 1+ were negative for HER2 overexpression. Among 231 patients, assessment of EGFR was performed in 204 patients, p53 in 132 patients, and Ki 67 in 228 patients. EGFR was considered as positive if membrane staining was observed. Ki 67 expression level of >=15% was considered as expression. Statistical Analysis Continuous variables are shown as means±standard deviation and categorical variables are presented as frequencies and percentages. The differences between the imaging findings for the TN cancer and non-tn cancer were compared using the unpaired t-test, Chisquare test and Fisher s exact test. In addition, logistic regression analysis was performed to assess the contribution of the major risk factors. Statistical significance was established at a p-value<0.05. Statistical analyses were performed using SAS version 9.1 (SAS Institute Inc., Cary, NC, USA). Results Forty three patients (18.6%) had TN breast cancer, Table 1. Characteristics of the 43 Triple Negative Breast Cancer and 188 Non Triple Negative Breast Cancer Groups Characteristics Triple Negative Breast Cancers (n=43) Non-Triple Negative Breast Cancers (n=188) P value Mean Age (year) Tumor Size (cm) Mean < 2 cm 16 (37.2%) 78 (41.5%) >=2 cm 27 (62.8%) 110 (58.5%) Histologic Grade < Grade 1 3 (7.0%) 40 (21.3%) Grade 2 10 (23.2%) 73 (38.8%) Grade 3 26 (60.5%) 38 (20.2%) Not Available 4 (9.3%) 37 (19.7%) Histologic Type Invasive ductal carcinoma 32 (74.4%) 151 (80.3%) Invasive lobular carcinoma 2 (4.7%) 3 (1.6%) Medullary carcinoma 5 (11.6%) 2 (1.1%) Mucinous carcinoma 0 2 (1.1%) Papillary carcinoma 0 2 (1.1%) Metaplastic carcinoma 1 (2.3%) 1 (0.5%) Mixed invasive carcinoma 0 2 (1.1%) Ductal carcinoma in situ 3 (7.0%) 25 (13.2%) EGFR Negative 17 (39.5%) 136 (72.3%) < Positive 20 (46.5%) 31 (16.5%) Not Available 6 (14.0%) 21 (11.2%) p53 Negative 13 (30.2%) 73 (38.8%) Positive 14 (32.6%) 32 (17.0%) Not Available 16 (37.2%) 83 (44.2%) Ki 67 Mean < < 15% 33 (76.7%) 76 (40.4%) < >= 15% 10 (23.3%) 109 (58.0%) Not Available 0 3 (1.6%) - 97-

15 Jae Jeong Choi et al and 188 patients (81.4%) had non-tn breast cancer. The characteristics of TN breast cancer and non-tn breast cancer are summarized in Table 1. The mean age was significantly older for the TN cancer group compared with the non-tn cancer group (p=0.019). There was no significant difference in the tumor size between two groups. TN breast cancers included invasive ductal carcinomas, medullary carcinomas, invasive lobular carcinomas, metaplastic carcinoma and ductal carcinoma in situ. Non-TN breast cancers included invasive ductal carcinoma, invasive lobular carcinoma, medullary carcinoma, mucinous carcinoma, papillary carcinoma, mixed carcinoma, metaplastic carcinoma and ductal carcinoma in situ. There were no significant differences in the histologic types between TN breast cancer and non-tn breast cancer groups. TN breast cancers were more likely to have high histologic grade tumors (p<0.0001). For the TN breast cancers, 26 breast cancers (67%) were grade 3. For the non-tn breast cancers, 38 breast cancers (25%) were grade 3. Compared with non-tn breast cancer, TN breast cancer was associated with EGFR positivity (p<0.0001), p53 overexpression (p=0.038), and Ki 67 expression (p<0.0001). Based on the multivariate analysis, a high histologic grade (odds ratio of grade 3 vs. grade 1, 9.1; 95% CI, ), p53 overexpression (odds ratio, 2.5; 95% CI, ), EGFR positivity (odds ratio, 5.2; 95% CI, ), and Ki 67 expression (odds ratio of < 15% vs. >= 15%, 4.9; 95% CI, ) were associated with the risk of TN breast cancer (Table 2). MRI Findings for TN Breast Cancer and non-tn Breast Cancer TN breast cancers (93.0%) were more likely to show mass-type than non-tn breast cancers (80.8%). However, there was no significant difference in the lesion type between TN breast cancers and non-tn breast cancers (p=0.055). Among mass-type lesions, 33 TN breast cancers (82.5%) showed round or oval or lobular shape. Irregular shape was found in 7 TN breast cancers (17.5%) and 69 non-tn breast cancers (45.4%). Irregular shape was significantly lesser in TN breast cancers than non-tn breast cancers (p=0.006) (Table 3). Smooth margins were more frequently found in TN breast cancers (37.5%) than non-tn breast cancers (23.0%). Spiculated margins were more frequently found in non-tn breast cancers (31.6%) than TN breast cancers (12.5%) (p=0.032). 25 TN breast cancers (62.5%) showed rim enhancement, which was significantly more than TN breast cancers (33.6%) (p=0.004). 59.9% of non-tn breast cancers showed heterogeneous enhancement (Fig. 1 and Fig. 2). There was no significant difference in the findings of nonmass lesions between TN breast cancers and non-tn breast cancers. Based on the multivariate analysis, the oval, round and lobular shapes (hazard ratio 3.92; 95% CI, ) and the rim enhancement (hazard ratio, 3.43; 95% CI, ) were associated with the risk of TN breast Table 2. Odds Ratios (95% CI) for the Triple Negative Breast Cancer Associated with Patient and Tumor Characteristics Triple Negative Cancers Odds Ratio (95% CI) Age (year) >= ( ) < (reference) Lesion Type on MRI Mass 3.16 ( ) Non-mass 1.0 (reference) Mass Shape Oval, Round, Lobular 3.92 ( ) Irregular 1.0 (reference) Mass Margin Smooth 2.01 ( ) Irregular, Spiculated 1.0 (reference) Mass Enhancement Homogeneous 1.4 ( ) Heterogeneous 1.0 (reference) Rim 3.43 ( ) Histologic Grade Grade (reference) Grade ( ) Grade ( ) p53 Negative 1.0 (reference) Positive 2.46 ( ) EGFR Negative 1.0 (reference) Positive 5.16 ( ) Ki 67 < 15% 1.0 (reference) >=15% 4.86 ( ) - 98-

16 MRI Findings of Triple Negative Breast Cancer Fig. 1. MRI finding for triple negative breast cancer in 42 year-old woman. T1-weighted sagittal MR image with contrast enhancement shows a lobular mass with smooth margins and a rim enhancement pattern. Fig. 2. MRI finding for non-triple negative breast cancer in 46 year-old woman. T1-weighted sagittal MR image with contrast enhancement shows an irregular mass with spiculated margins and a heterogeneous enhancement pattern. cancer (Table 2). Discussion Triple negative breast cancer has been reported in 10-25% of all types of breast cancer. It occurs with a higher incidence in pre-menopausal African/American women (1-4). In our study, TN breast cancer accounted for 18.6% of all types of breast cancers. Patients with TN breast cancer were older than those with non-tn breast cancer. This result was similar to the findings obtained for the Japanese series (2). In our study, 93% of the TN breast cancers were mass-type lesions on MRI. Several studies have reported that TN breast cancer is more likely to exhibit mass on MRI and mammography (5-7). However, there was no significant difference in the lesion type between TN breast cancers and non-tn breast cancers in our study. This result may be due to the fact that 28 DCIS were included in our study. Non-mass type enhancement is a common feature of DCIS on MRI (8, 9). We found that the lobular shape, smooth margins, and rim enhancement are associated with TN breast cancers. Because TN breast cancers have an aggressive growing nature, they may reveal bulging shape with pushing borders. Rim enhancement may be due to tumor necrosis. Uemastu T, et al. reported that a very high intratumoral signal intensity on T2-weighted MR images is associated with intratumoral necrosis (5). In contrast, non-tn breast cancers were associated with spiculated margins, due to the desmoplastic reaction of the tumor. Metaplastic carcinoma and medullary carcinoma show a basal-like subtype, and they have higher incidences in TN breast cancer (10-15). Our study included five medullary carcinomas and one metaplastic carcinoma in 43 TN breast cancers. The frequency of the histologic types did not differ between the TN breast cancers and the non-tn breast cancers. This result may be due to the small number of TN breast cancers evaluated. In our study, EGFR, p53 and Ki 67 were overexpressed in TN breast cancer. We assumed that aggressiveness and rapid growing of TN breast cancer - 99-

17 Jae Jeong Choi et al Table 3. MRI findings for the 43 Triple Negative Breast Cancer and 188 Non Triple Negative Breast Cancer Groups MRI Findings Triple Negative Cancers (n=43) Non-Triple Negative Cancers (n=188) Lesion Type Mass 40 (93.0%) 152 (80.9%) Non-mass 03 (7.0%) 036 (19.1%) Mass Shape Round, Oval 16 (40.0%) 041 (27.0%) Lobular 17 (42.5%) 042 (27.6%) Irregular 07 (17.5%) 069 (45.4%) Mass Margins Smooth 15 (37.5%) 035 (23.0%) Irregular 20 (50%) 069 (45.4%) Spiculated 05 (12.5%) 048 (31.6%) Mass Enhancement Homogeneous 02 (5.0%) 010 (6.6%) Heterogeneous 13 (32.5%) 091 (59.9%) Rim 25 (62.5%) 051 (33.5%) Non-mass Distribution Focal 01 (33.3%) 005 (13.9%) Segmental 02 (66.7%) 028 (77.8%) Regional 00 ( 003 (8.3%) Non-mass Enhancement Homogeneous 00 ( 005 (13.9%) Heterogeneous 01 (33.3%) 015 (41.7%) Stippled, Punctuate 00 ( 002 (5.5%) Clumped 02 (66.7%) 014 (38.9%) P value related to overexpression of the markers. EGFR, a type of cell surface receptor, is associated with cell proliferation. EGFR has been considered as a potential therapeutic target in TN breast cancer (16). p53 is a tumor suppression gene that regulates cell proliferation and apoptosis (17). p53 overexpression is an indicator used to predict the response to anthracycline-based chemotherapy in breast cancer. They are associated with a poor prognosis (16-21). Ki 67 is a nuclear antigen that appears during the proliferative phase of the cell cycle. It is related to a high mitotic count and a high level of cell proliferation (22-24). Our study has limitations. First, a small number of patients were enrolled. Further validation in a larger study is warranted. Second, we used only immunohistochemistry to define HER2 status. We classified the HER2 2+ score as positive for HER2 overexpression, without considering the results of fluorescence in situ hybridization (FISH). However, the definition of HER2 status in TN breast cancer remains controversial. Third, inter-observer variability in the assessment of BI-RADS-based MRI findings was not considered in the present study. However, two radiologists reached a consensus in the evaluation of the MRI findings. In conclusion, TN breast cancer occurred in elderly women. On MRI, rim enhancing mass with round or oval or lobular shape is favorable to TN breast cancer rather than non-tn breast cancer. It may be due to aggressive histologic behavior of TN breast cancer. MRI finding may be helpful for planning treatment and prediction prognosis in triple negative and non-triple negative breast cancer patients. References 1.Reis-Filho JS, Tutt AN. Triple negative tumours: a critical review. Histopathology 2008;52: Iwase H, Kurebayashi J, Tsuda H, et al. Clinicopathological analyses of triple negative breast cancer using surveillance data from the Registration Committee of the Japanese Breast Cancer Society. Breast Cancer 17: Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast

18 MRI Findings of Triple Negative Breast Cancer cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007;13: Trivers KF, Lund MJ, Porter PL, et al. The epidemiology of triple-negative breast cancer, including race. Cancer Causes Control 2009;20: Uematsu T, Kasami M, Yuen S. Triple-negative breast cancer: correlation between MR imaging and pathologic findings. Radiology 2009;250: Chen JH, Agrawal G, Feig B, et al. Triple-negative breast cancer: MRI features in 29 patients. Ann Oncol 2007;18: Yang WT, Dryden M, Broglio K, et al. Mammographic features of triple receptor-negative primary breast cancers in young premenopausal women. Breast Cancer Res Treat 2008;111: Facius M, Renz DM, Neubauer H, et al. Characteristics of ductal carcinoma in situ in magnetic resonance imaging. Clin Imaging 2007;31: Rosen EL, Smith-Foley SA, DeMartini WB, Eby PR, Peacock SLehman CD. BI-RADS MRI enhancement characteristics of ductal carcinoma in situ. Breast J 2007;13: Weigelt B, Kreike B, Reis-Filho JS. Metaplastic breast carcinomas are basal-like breast cancers: a genomic profiling analysis. Breast Cancer Res Treat 2009;117: Reis-Filho JS, Milanezi F, Steele D, et al. Metaplastic breast carcinomas are basal-like tumours. Histopathology 2006;49: Leibl S, Moinfar F. Metaplastic breast carcinomas are negative for Her-2 but frequently express EGFR (Her-1): potential relevance to adjuvant treatment with EGFR tyrosine kinase inhibitors? J Clin Pathol 2005;58: Reis-Filho JS, Milanezi F, Carvalho S, et al. Metaplastic breast carcinomas exhibit EGFR, but not HER2, gene amplification and overexpression: immunohistochemical and chromogenic in situ hybridization analysis. Breast Cancer Res 2005;7: R Kuroda N, Fujishima N, Inoue K, et al. Basal-like carcinoma of the breast: further evidence of the possibility that most metaplastic carcinomas may be actually basal-like carcinomas. Med Mol Morphol 2008;41: Sasaki Y, Tsuda H. Clinicopathological characteristics of triple-negative breast cancers. Breast Cancer 2009;16: Corkery B, Crown J, Clynes M, O Donovan N. Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer. Ann Oncol 2009;20: Rolland P, Spendlove I, Madjd Z, et al. The p53 positive Bcl-2 negative phenotype is an independent marker of prognosis in breast cancer. Int J Cancer 2007;120: Viale G, Rotmensz N, Maisonneuve P, et al. Invasive ductal carcinoma of the breast with the triple-negative phenotype: prognostic implications of EGFR immunoreactivity. Breast Cancer Res Treat 2009;116: Biswas DK, Iglehart JD. Linkage between EGFR family receptors and nuclear factor kappab (NF-kappaB) signaling in breast cancer. J Cell Physiol 2006;209: Nogi H, Kobayashi T, Suzuki M, et al. EGFR as paradoxical predictor of chemosensitivity and outcome among triplenegative breast cancer. Oncol Rep 2009;21: Chae BJ, Bae JS, Lee A, et al. p53 as a specific prognostic factor in triple-negative breast cancer. Jpn J Clin Oncol 2009;39: Yamamoto Y, Ibusuki M, Nakano M, Kawasoe T, Hiki R, Iwase H. Clinical significance of basal-like subtype in triplenegative breast cancer. Breast Cancer 2009;16: Viale G, Regan MM, Mastropasqua MG, et al. Predictive value of tumor Ki-67 expression in two randomized trials of adjuvant chemoendocrine therapy for node-negative breast cancer. J Natl Cancer Inst 2008;100: Ding SL, Sheu LF, Yu JC, et al. Expression of estrogen receptor-alpha and Ki67 in relation to pathological and molecular features in early-onset infiltrating ductal carcinoma. J Biomed Sci 2004;11:

19 Jae Jeong Choi et al 대한자기공명의과학회지 14:95-102(2010) 삼중음성유방암의자기공명영상소견 : 비삼중음성유방암과의비교 1 가톨릭대학교의과대학영상의학과 2 가톨릭대학교의과대학임상연구지원센터 3 가톨릭대학교의과대학외과 최재정 1 김성헌 1 차은숙 1 강봉주 1 이지혜 1 이소연 1 정승희 2 임현우 2 송병주 3 목적 : 삼중음성유방암은국소재발및원격전이가흔하고예후가불량한유방암이다. 이의자기공명영상소견과임상적, 병리학적소견이비삼중음성유방암과차이가있는지알아보고자한다. 대상및방법 : 2007년부터 2008년까지수술로확진된 231명의유방암환자를대상으로하였다. 자기공명영상소견에서대표병변을 Breast Imaging Reporting and Data System (BI-RADS) 에따라후향적으로분석하였고삼중음성유방암의소견이비삼중음성유방암과차이가있는지알아보았다. 또한나이, 조직학적형태, 분화도, 표피성장인자수용체, p53, Ki 67의발현정도가두군간에차이가있는지분석하였다. 결과 : 총 231명중 43명 (18.6%) 이삼중음성유방암이었다. 삼중음성유방암중 40개 (93%) 가자기공명영상에서종괴병변이었다. 삼중음성유방암은비삼중음성유방암에비해원형, 난원형또는소엽성모양 (p=0.006), 변연조영증강 (p=0.004) 소견이많았다. 반면불규칙모양 (p=0.006) 과침상경계 (p=0.032) 는비삼중음성유방암에유의하게많았다. 고령 (p=0.019), 높은조직분화도 (p < ), 표피성장인자수용체양성 (p < ), p53 (p=0.038) 과 Ki 67 (< ) 과발현이삼중음성유방암과관련이있었다. 결론 : 자기공명영상소견은삼중음성유방암과비삼중음성유방암을구분하는데도움이된다. 통신저자 : 김성헌, ( ) 서울시서초구반포동 505, 가톨릭대학교의과대학서울성모병원영상의학과 Tel Fax rad-ksh@catholic.ac.kr

20 정상노인및경도인지장애및알츠하이머성치매환자에서의한국인뇌구조영상표준판개발 김민지 1, 2 장건호 2 이학영 3 김선미 2 류창우 2 신원철 3 이수열 1 목적 : 자기공명영상을이용한치매연구에서삼차원 T1강조뇌구조영상으로뇌기능을분석할경우복셀기반형태분석방법이이용된다. 그러나일반적으로 The Montreal Neurological Institute (MNI) 152 라는젊은서양성인뇌로만들어진표준판에정규화되고이는분석오차가생길수있어한국노인및치매환자의뇌를분석할경우부정확한결과를초래한다. 따라서, 본연구의목적은뇌분석을최적화하기위해한국노인및치매환자의뇌구조영상의표준판을개발하는데있다. 대상및방법 : 검사장비는 3테슬러를이용하였으며 8채널 SENSE (sensitivity encoding) 머리코일을이용하였다. 펄스열은삼차원 T1 강조터보경사자장타입으로뇌의해부학영상을획득하였다. 신경심리검사점수결과에따라정상노인 43명, 경도인지장애환자 44명, 알츠하이머성치매환자 36명의세그룹으로나누었다. 일반선형모델방정식을사용하여나이와성별및질환간의차이에의한인자를고려하였으며, 평가된인자는쌍일치접근방법으로한국노인과치매환자의뇌표준판을만들었다. 두표준판의 Talairach 기준점에따른평균거리와뇌실의거리를계산하였다. 또한뇌전체영역에서회백질과백질을확률이 50% 이상인복셀개수를세어회백질과백질의영역을계산하였다. 결과 : 최종뇌표준판은 MNI152뇌표준판과비교했을경우공간분해능이높았고, 평균거리와뇌실의크기에서차이가있었다. 회백질및백질의영역은본연구에서개발한뇌표준판의회백질과백질모두에서더적었고, 백질보다회백질에서더많은차이가있었다. 결론 : 본연구에서개발한한국뇌표준판은앞으로한국노인과치매환자의질환을분석하는연구에유용할것으로생각된다. 서론구조적자기공명영상 (Structural Magnetic Resonance Imaging, MRI) 과기능적자기공명영상 (functional Magnetic Resonance Imaging, fmri) 을이용한임상적용및인지과학연구가많이진행되고있다. 현재가장많이사용 되는대표적인뇌구조펄스열 (pulse sequence) 로삼차원 T1 강조 (3Dimension-T1 Weighted Imaging) 영상을얻을수있는 MPRAGE (Magnetization Prepared Rapid acquisition Gradient Echo) (1) 혹은 SPGR (Spoiled Gradient-Recalled) (2) 방법이있다. 삼차원 T1강조뇌구조영상을이용한특정영역을분석하기위하여관심영역 (Region of interest, ROI) 방법이사용되나, 이방법은주관적인판단 대한자기공명의과학회지 14: (2010) 1 경희대학교대학원생체의용공학과 2 경희대학교의과대학강동경희대학교병원영상의학과 3 경희대학교의과대학강동경희대학교병원신경과 * 본연구는보건복지가족부보건의료연구개발사업의지원에의하여이루어진것임 (A092125). 접수 : 2010 년 9 월 30 일, 수정 : 2010 년 11 월 29 일, 채택 : 2010 년 11 월 30 일통신저자 : 장건호, ( ) 서울시강동구상일동 149 번지, 경희대학교의과대학부속강동경희대학교병원영상의학과 Tel. (02) Fax. (02) ghjahng@gmail.com

21 김민지외 에의해평가에오차가존재할수있다 (3). 복셀기반형태분석 (Voxel-Based Morphometry, VBM) 을통한삼차원T1강조뇌구조영상방법은회백질감소 (gray matter loss) 또는백질의신호강도를이용한특정부위의부피차이를관찰하는방법으로두뇌전체를분할 (Segmentation) 하여뇌의전체적인변화를객관적으로조사할수있다는장점을가지고있다 (4). VBM 분석을위해서는뇌표준판 (brain template) 에맞춰공간정규화 (Spatial normalization) 하는과정을통하여위치정보를얻는다 (5). 현재삼차원 T1강조영상뿐만아니라뇌확산강조 (diffusion-weighted imaging, DWI) 및확산텐서 (diffusion tensor imaging, DTI) 혹은동맥라벨링 (arterial spin labeling, ASL) 을이용한뇌관류 (cerebral perfusion imaging) 에서도 VBM 방법을이용한뇌변화연구가활발하게진행되고있다. 이때에도삼차원 T1강조영상을이용한뇌표준판을많이이용하게된다. 최근들어고령인구의급격한증가때문에 MRI를이용한치매환자에대한뇌연구가많이진행되고있다. 치매는나이가들어감에따라뇌가후천적인외상이나질병등외부적인요인에의해손상되거나파괴되어점진적인기억력장애와함께한가지이상의인지기능장애를말하며뇌의조직학적변화가나타난다 (6). 노인치매의종류에는여러가지가있는데그중에서알츠하이머성 (Alzheimer s disease) 은치매의 50% 를차지할정도의기억, 사고및행동에장애를초래하는뇌의진행성, 퇴행성질병이다. 노인및치매환자에대한뇌연구를할경우에도 VBM을통한분석이필요하다 (7, 8). 이는해마 (hippocampus) 혹은내후각내피질 (entorhinal cortex) 과같은조직의손상또는특질상취약한뇌영역을관찰하므로정상노인에서경도인지기능장애 (Mild Cognitive Impairment, MCI) 혹은알츠하이머성치매 (Alzheimer s disease, AD) 환자로전환됨을예측할수있다 (9). 그예로, 알츠하이머성치매환자에서 3차원뇌구조 T1 강조영상을이용한회백질감소 (7, 10), 알츠하이머성치매에서 Voxel-based DTI 분석 (11), 알츠하이머성치매에서 ASL를이용한 perfusion 분석 (12) 등이보고된바있다. 현재쥐 (13), 토끼 (14) 등의동물의뇌, 신생아 (15) 혹은젊은정상한국인 (16, 17) 혹은국내어린이 (18) 등을대상으로한표준판이개발되었으며계속해서임상에필요한여러표준판들이개발중에있다. 이들표준판을이용할경우각연구에서보고한것과같이개개의객체를표준좌표화하여군간비교를하거나개개인분석을할경우보다정밀하게분석을할수있는특징이있다. 따라서분석결과의신빙성을높이기위해서는연구하고자하는객체에대한특정표준판을만들어서사용하는것이바람직하다. 일반적으로VBM 분석을위해서많이사용되는뇌표준판은몬트리올신경과학연구소 (Montreal Neurological Institute, MNI) 152 에서개발한뇌표준판을사용하고있다. MNI 표준판을통해뇌영상을맞출때개개인의뇌를 Talairach 좌표로 표준좌표화하여이용하고있다 (19). MNI152 표준판은평균연령이27.8세 (± 5.1) 로젊은정상청년의뇌를이용하여만들어졌으며오른손잡이서양인의뇌를바탕으로하고있다 (20). 한국인노인과치매에대한뇌영상을분석할경우에도서양성인을기준으로한뇌표준판에맞추게된다. 하지만유럽인과일본인의뇌형태를비교했을때인종이나성별에따라서뇌반구의크기와모양이다르다고보고하였다 (21). 또한연령과성별에따른정상한국인뇌실의계측학적연구에서연령이높을수록뇌실의크기가크다고보고되었다 (22). 그러므로 MNI 뇌표준판로한국노인뇌를분석할경우, 인종에의한오차나연령과성별에의한형태적기능적인오차가생길수있어한국인의노화에따른뇌기능연구에부정확한결과를가져올수있다. 이때문에어린환자군혹은나이가많은노인환자군에서얻은영상을분석하기위해서는연구중심의표준화된특정뇌표준판이필요하다. 현재까지어린이뇌를바탕으로하거나 20대와 40대한국인정상남녀를대상으로한뇌표준판은많이보고되었으나, 아직까지한국노인이나치매환자를위한한국인뇌표준판에대한자료가부족한실정이다. 따라서본연구의목적은 50대에서 80대사이의한국정상노인 (Cognitive Normal), 경도인지장애 (Mild Cognitive Impairment) 환자, 알츠하이머성치매 (Alzheimer s disease, AD) 환자군의삼차원T1강조영상을각회백질 (Gray matter), 백질 (White matter) 뇌척수액 (Cerebrospinal Fluid) 의조직맵 (tissue maps) 으로분할한뒤특정뇌표준판을만들고 MNI152 표준판과비교하여한국노인및치매환자의뇌분석을최적화하기위한방법을연구하는데있다. 대상및방법대상본연구는연구를주관한기관의임상실험인증을받은후에실시하였으며, 모든피험자에서참여동의서를획득하고연구를진행하였다. 대상군은표준신경심리검사 (Seoul Neuropsychological Screening Battery, SNSB) 를수행하고 MRI뇌영상을얻었다. SNSB검사는주의집중능력, 언어및그와관련된기능, 시공간기능, 기억력및전두엽, 집행기능의 5가지인지영역을평가함으로써치매환자를진단하는신경심리검사이다. 피험자군의분류는 SNSB 검사를바탕으로이루어졌다. 본연구에참여한총피험자는 148명이었으며이중 25명은피험자의움직임이나 MRI뇌영상을판독한결과뇌에병변이있는경우로본연구에서배제되었다. 최종적으로정상노인 43명 ( 평균나이64.9세 ; 표준편차7.6세 ; 나이범위50-82세 ; 남자15 명, 여자28명 ), MCI환자44명 ( 평균나이67.7세 ; 표준편차7.69 세 ; 나이범위50-83세 ; 남자20명, 여자22명 ),AD환자36명 ( 평균나이72.7세 ; 표준편차9.2세 ; 나이범위53-87세 ; 남자7명, 여자29명 ) 이본연구에포함되었다. 이들을정리한내용이 Table 1에있다

22 정상노인및경도인지장애및알츠하이머성치매환자에서의한국인뇌구조영상표준판개발 삼차원 T1 강조 MRI 영상획득검사장비는 3테슬러 (Tesla) 자기공명영상장치 (Philips, Achieva, Best, The Netherlands) 를이용하였으며 8 채널 SENSE (Sensitivity encoding) 머리코일을이용하였다. 사용한펄스열 (pulse sequence) 은뇌척수액신호를최소화시킬수있는반전 (inversion recovery) T1 강조터보경사자장타입의삼차원T1강조영상이고, 사용된인자는다음과같다. 반향시간 (echo time, TE)=3.7 ms, 반복시간 (repetition time, TR)=8.1 ms, 반전시간 (inversion time, TI)= ms, 시야 (field of view)= mm, 매트릭스크기 (matrix size)= mm, 복셀크기 (voxel size)=1 1 1 mm, 영상획득방향 = 시상면 (sagittal), 절편두께 (slice thickness)=1 mm, 절편수 (Slice)=326, 슬라이스방향평행인자 (SENSE factor)=2.5, 숙임각 (Flip angle)=8 로총영상획득시간은 4분 35초였다. per class = voxels로하였고지역적으로이미지를최적화하기위해아핀조정 (affine Regularisation) 과조직맵을등록시키기위한뒤틀림조정 (Warping Regularisation)=1, 뒤틀림주파수끊어버림 (Warp Frequency cutoff) 은 25 mm로하였으며비선형조정 (nonlinear regularization) 은 very light regularization 으로하였다. FWHM (full width half maximum) 은 70 mm 로중첩적분하여편평화 (smoothing) 하였다. 회백질, 백질, 뇌척수액의조직맵을평균영상에비선형방법 (Non-linear only) 으로정규화하고최종적으로삼차원복셀크기를 mm로하였다. 분할은변화가없으면끝나도록하였으며, 뇌구조영역분할 (segmentation) Fig. 1에서는본연구에서뇌표준판을얻기위하여사용한각단계를나타내고있다. 영상을표준판으로정합하는과정의오차를줄이기위하여총 123명각각의삼차원 T1강조뇌영상을전교련 (anterior commissure, AC) 과후교련 (posterior commissure, PC) 선을중심으로위치조정하였다. 다음으로 SPM5 (Statistical Parametric Mapping 5, Wellcome Departmentof Imaging Neuroscience, University College London, UK) 프로그램에서제공한 VBM5(Voxel-Based Morphometry 5) 소프트웨어 [23] 를사용하여각삼차원 T1강조뇌구조를회백질 (Gray Matter), 백질 (White Matter), 뇌척수액 (Cerebrospinal Fluid) 의조직맵 (Tissue maps) 으로분할하였다. 회백질, 백질, 뇌척수액과각각에공유되는 cluster의세기분포를위해 Gaussians Table 1. Demographic Data of Study Population CN MCI AD Subjects *Age (years± SD) 64.9 (±7.6) 67.7 (±7.6) 72.7 (±9.2) # Gender Male Female Data are listed as the mean ± standard deviation. CN: Cognitive Normal. MCI: Mild Cognitive Impairment. AD: Alzheimer s disease. # Gender: statistically significant difference between MCI and AD (p = 0.007), but no significant differences between CN and MCI (p = 0.22) or between CN and AD (p = 0.13) *Age: statistically significant difference between CN and AD (p = ) and between MCI and AD (p = 0.01), but no significant d- ifference between CN and MCI (p = 0.08) Fig. 1. Flowchart for the brain template creation. In this study, we use two separated steps, VBM5 and TOM. GM: Gray matter WM: White matter CSF: Cerebrospinal Fluid VBM: Voxel-Based Morphometry TOM: Template-O-Matic

23 김민지외 만일변화가있으면다시처음부터모든과정을되풀이하였다 (24). 뇌구조영상표준판 (brain template) 생성 VBM5를이용하여얻은모든대상의삼차원T1강조영상과분할된조직맵 ( 회백질, 백질, 뇌척수액 ) 의뇌표준판을만들기위해 SPM5프로그램의 TOM (Template-O-Matic) 소프트웨어를사용하였다 (25). 표준판을만드는과정은평가 (estimation) 와표준판생성 (creation) 두단계로이루어졌다. 첫번째평가단계는나이 (age) 와성별 (gender), 환자군 (differential diagnosis, DDX) 에따른영향을고려하기위하여다중회기모델 (multiple regression model) 을사용하였다. 나이를인자로사용한이유는전체피험자의나이분포가 50~87세로넓게분포되었기때문이며, 나이에대한회귀모델 (regression model) 을 3차다항식으로계산을하였다 (26). 성별을인자로사용한이유는치매환자가대체적으로여성에많이발병되고본연구에이용된피험자의경우남자와여자간의성별의차이가있기때문이다. 또한환자군을인자로사용한이유는세가지 ( 정상군, 경도인지장애군, 치매환자군 ) 다른군간의 차이점을보정해주기위해서이다. 따라서우리의모델을평가하기위하여일반선형모델 (general linear model) 방정식을사용하였고최종적으로나타나는영상은각복셀에대한나이에따른 4개의인자와하나의성별및하나의 DDX 차이에따른조직맵을얻었다. 다음으로위에서얻어진평가된파라미터인자를이용하여각각의변수와피험자에대한 T1강조영상 (Whole brain) 과조직맵 ( 회백질, 백질, 뇌척수액 ) 을만든후최종적으로평균된표준판을만드는방법인쌍일치접근법 (Matched pairs approach) 을사용하여최종표준판생성하였다. 뇌표준판의평가 Fig. 2는완성된한국노인및치매환자의뇌표준판과 SPM5에서제공된 MNI152 뇌표준판의각기준점들간의평균거리를나타낸영상이다. 뇌의모양과크기를조사하기위해 8개의 Talairach 기준점 (Talairach reference point) 이정의되었다 (19). 본연구에서는이중에서 6개의기준점을선택하여각기준점들간의거리를계산하였고정의된기준점은다음과같다. Anterior Point (AP) 는이마엽겉질의가장앞 Fig. 2. Measured parameters shown on the images of the smoothed our brain template (a, c) and the MNI- 152 template (b, d). The solid lines show the center position (0, 0, 0) in x, y z plane. The upper and lower dotted lines show the length of the SP-IP size and the middle dotted line is the length of the AP-PP line. The vertical lines show the length of the RP-LP line. a b c d

24 Table 2. Charateristics of the Two Standard Brain Templates 정상노인및경도인지장애및알츠하이머성치매환자에서의한국인뇌구조영상표준판개발 MNI152 # Template size (mm) # Resolution (mm) *Age effect (±5.1): No (±8.6): Yes *Gender effect (M/F) M (n=52)/f (n=48): No M (n=42)/f (n=81): Yes *DDX CN (n=100): No CN (n=43)/mci (n=44)/ad (n=36): Yes &ngm &nwm X=AP-PP(mm) Y=RP-LP(mm) Z=SP-IP(mm) ventricle _a (mm) ventricle _b (mm) ventricle _c (mm) ventricle _d (mm) ventricle _e (mm) # Template size (mm) and resolution (mm): X Y Z. *Age, gender and DDX effects were considered in our template (Yes), but not in the MNI (No). & normalized gray matter or white matter percentage: ngm or nwm equals to the number of GM voxels multipled by 100% devided by the total IC voxels more than 50% of GM or WM, respectively. DDX: differential diagnosis, GM: gray matter, WM: white matter, IC: Intracranial, AP: anterior point, PC: posterior point, RP-LP: right point-left point, SP-IP: superior point- inferior point OURS Fig. 3. Measured distances (mm) of the ventricle area for selecting landmark sites in the MNI-152 template (Upper left and bottom left) and the smoothed our brain template (Upper right and bottom right)

25 김민지외 의점으로, Posterior Point (PP) 는뒤통수엽겉질의가장뒤의점이다. 오른쪽지점 (Right point, RP) 은우반구마루엽관자엽겉질의가장가쪽의점으로, 왼쪽지점 (Left point, LP) 은좌반구마루엽관자엽겉질의가쪽의점으로, (Superior point, SP) 는마루엽겉질의가장위의점으로, (inferior point, IP) 는관자엽겉질의가장아래의점이다. a 와 b영상은각각한국노인및치매환자에서의뇌표준판과 MNI152뇌표준판을시상면으로나타낸것이다. 실선은 x, y, z 좌표에서 (0, 0, 0) 을갖는중심점을나타내고맨위와맨아래흰색점선들은각각 SP와 IP를나타낸다. 가운데흰색점선은 AP와 PP선을지나는기준점이다. c와 d는각각한국노인및치매환자의뇌표준판과 MNI152 표준판을횡단면으로나타낸영상이다. 수직으로표시된흰색점선들은각각 RP를지나는선과 LP를지나는선을나타낸다. 본연구에서는각각의평균거리를수동으로계산하였으며이것을정리한내용이 Table 2에있다. Fig. 3 은뇌실의크기를계산하기위해 a부터 e까지의특정거리를선택하였고각각을흰색점선으로표시하였다. 왼쪽영상은 MNI152 뇌표준판의시상면 ( 위 ) 과횡단면 ( 아래 ) 을보여주고있고, 오른쪽영상은한국노인및치매환자뇌표준판의시상면 ( 위 ) 과횡단면 ( 아래 ) 를보여주고있다. a부터 e까지거리를계산한결과는 Table 2에정리하였다. 결과 Table 1은본연구에참여한피험자의수와그에따른각군에서의평균연령및성별결과이다. student t-test를이용한각군간의성별의차이는정상인과 MCI환자 (p = 0.22) 와정상인과 AD환자 (p = 0.13) 사이에서통계적으로유의한차이가없었지만 (p > 0.05), MCI환자와 AD환자간 (p = 0.007) 에는성별에따른유의한차이가있었다 (p < 0.05). 나이에따른차이에서정상인과 MCI환자 (p = 0.08) 에서차이가없었고 (p > 0.05), 정상인과AD환자 (p = ) 및 MCI환자와AD환자 (p = 0.01) 간의비교에서는유의한차이가있었다 (p < 0.05). 성별과나이에유의한차이가있었으므로, 본연구에서만드는뇌표준판에전체피험자의성별을공변량값으로사용하였고, 전체피험자에대한나이와 3개의피험자군 (CN, MCI, AD) 에대해서도뇌표준판을생성할때에공변량값으로사용하였다. Fig. 4는 VBM5 소프트웨어를이용한대표적인각한명의정상인 (CN), MCI환자, AD환자에대한공간정규화후의삼차원 T1강조 (Whole brain) 및회백질 (GM), 백질 (WM), 뇌척수액 (CSF) 조직맵의분할한결과이다. 세명모두에서조직맵이명확하게관찰됨을확인할수있다. 본연구에서사용한 VBM5 소프트웨어가정상인과환자군모두에서조직맵을잘 Fig. 4. Representative segmented images obtained in a cognitively normal (CN) control subject (upper row), in a patient with mild cognitive impairment (MCI, middle row), and in a patient with Alzheimer s disease (AD, bottom row). Each subject is a 70 years-old woman. GM: Gray matter WM: White matter CSF: Cerebrospinal Fluid

26 정상노인및경도인지장애및알츠하이머성치매환자에서의한국인뇌구조영상표준판개발 분할하여뇌표준판및표준조직맵이생성되는데큰문제가없음을알수있었다. Fig. 5은 TOM 소프트웨어를이용하여쌍일치접근 (matched pairs approach) 방법을이용한전체피험자에서얻은삼차원뇌표준판 (Fig. 3a) 과그에따른회백질 (Fig. 3b), 백질 (Fig. 3c), 뇌척수액 (Fig. 3d) 조직맵의표준뇌영상이다. 현재 SPM5에서사용하고있는 MNI152 뇌표준판에서복셀크기 mm과비교하면노인및치매환자의뇌표준판의복셀크기는 mm로공간분해능 (spatial resolution) 이높았다. Fig. 6은 Fig. 5a에서보여준 3차원 T1 표준영상을 2차원횡단면뇌표준판 (transverse brain template) 으로다시보여준영상이다. 시야는 mm로 MNI152 표준판의시야 mm와비교할때매우높은신호와해상도를보여주고있다. Fig. 7은최종뇌표준판평가 (estimation) 과정에서일반선형모델 (general linear model) 방정식을이용한값에따른피험자군에대한 3차원 T1영상및조직맵 ( 회백질, 백질, 뇌척수액 ) 표준판의최소제곱방법의변수에따른변화 (beta) 이 다. 나이인자 (age) 는회귀모델 (regression model) 을 3차다항식으로정의하여계산한결과값이고, 전체피험자에대한성별인자 (gender) 및환자군간의인자 (DDX) 에따른변화가나타나있다. Table 2는정규화된 MNI152표준판과본연구에서개발한뇌표준판각각의특징을비교한결과이다. 회백질과백질은뇌전체영역중에서회백질과백질의영역을확률이 50% 이상인복셀개수를세어계산하였다. 회백질의경우한국노인및치매환자의뇌표준판은 MNI152에비하여약 20% 적었고, 백질의경우 2.2% 더적었다. 대체적으로본연구에서개발한뇌표준판의회백질과백질의영역이작았고, 백질보다회백질에서더많은차이가있었다. 고찰본연구에서는자기공명영상을이용한한국노인및치매환자에서뇌기능의활성화된영역을찾기위한복셀기반형태분석 (Voxel-Based Morphometry, VBM) 을위하여삼차원T1 강조뇌구조영상을분할하고특정뇌표준판을만드는연구를 Fig. 5. The created standard brain templates of three-dimensional T1- weighted (a) and the corresponding tissue maps of gray matter(gm, b), white matter (WM, c), andcerebrospinal fluid (CSF, d). a b c d

27 김민지외 시행하였다자기공명영상은점차고령화가가속화함에따른한국인노인및알츠하이머성치매환자의활성화된뇌영역을분석하는연구에널리기여하고있다 (27). 특히삼차원T1강조혹은삼차원MPRAGE 뇌구조영상방법을이용한뇌세포분할과회백질의위축 (atrophy) 의분석등을통한조직의손상또는특질상취약한뇌영역의관찰과뇌기능의활성화된영역을찾기위한복셀기반형태분석방법이가장보편적으로사용되고있다 (4). 그예로알츠하이머성치매환자에서삼차원뇌구조 T1 강조영상을이용한회백질감소혹은 Voxel-based DTI (11) 분석혹은알츠하이머성치매환자에서ASL을이용한뇌관류영상분석 (12) 등이보고된바있다. 이러한알츠하이머성치매에서의형태분석을위해각대상자의삼차원T1강조영상을뇌표준판 (brain standard template) 에맞춰공간정규화 (spatial normalization) 하여위치정보를얻는다 (5). SPM프로그램에서일반적으로사용되는표준뇌모형은서양의젊은성인 ( 평균 27.8세, 표준편차 5.1) 으로만든 MNI152 표준판이다 (20). MNI152표준판에직접한국노인및치매환자의뇌를공 간정규화할경우인종또는성별, 나이에따른형태학적, 기능적오차로인해부정확한정보를제공할수있다 (21, 22). 평균한국인뇌의길이와 MNI 뇌표준판의길이를비교한연구에서한국인평균세로길이는남자는 16.5 cm, 여자는 15.6 cm로, 가로길이는남자는 14.3 cm, 여자는 13.5 cm로, 높이길이는남자는 12.1 cm, 여자는 11.4 cm로 MNI의뇌에서세로 18.3 cm, 가로 14.2 cm, 높이 13.3 cm와비교할때많은차이가있다고보고되었다 (17). 이러한오차때문에각대상자에맞는뇌표준판을만드는연구가많이진행되고있는데현재까지동물을대상으로한뇌표준판과 (13, 14), 신생아 (15) 혹은 20대에서 40대사이의정상한국인 (16, 28) 혹은국내어린이 (18) 등을대상으로한표준판이개발되었으며계속해서임상에필요한여러표준판들이개발중에있다. 그러나아직까지한국노인이나치매환자를위한한국인뇌표준판에대한자료가부족한실정이고나이가많은노인환자군에서얻은영상을분석하기위해서는연구중심의표준화된특정뇌표준판이필요하다. 본연구에서구조영역별표준판을완성하기위하여 SPM5프 Fig. 6. The created standard brain template of three-dimensional T1-weighted images was shown as the axial plane slices

28 정상노인및경도인지장애및알츠하이머성치매환자에서의한국인뇌구조영상표준판개발 로그램에서제공된VBM5 소프트웨어 (23) 를이용하여뇌구조를회백질 (Gray matter, GM), 백질 (White matter, WM) 및뇌척수액 (Cerebrospinal Fluid, CSF) 으로분할하여조직맵 (tissue maps) 으로구분하였다. 그결과각각의조직맵이명확하게관찰되었고본연구에서사용한 VBM5 소프트웨어가정상인과환자군모두에서조직맵을잘분할하여뇌표준판및표준조직맵이생성되는데큰문제가없음을알수있었다 (Fig. 2). 분할된구조조직별뇌표준판을만들기위해 TOM 소프트웨어 (25) 를이용한두단계를시행하였다. 첫번째단계는평가 (estimation) 로서나이와성별, 환자군차이에따른영향을얻기위하여다중회기모델 (multiple regression model) 방정식을사용하여변수에따른변화값 (beta) 을얻는과정이다. 나이를인자로사용한이유는전체피 험자의나이분포가 50~87세로넓게분포되었기때문이며나이에대한회기모델 (regression model) 로는 3차 (cubic) 로선택하여 3차다항식으로정의하여계산되었다 (26). 성별을인자로사용한이유는치매환자가대체적으로여성에많이발병되고본연구에이용된피험자의경우남자와여자간의성별의차이가있기때문에인자로선택하였고환자군차이를인자로사용한이유는세가지 ( 정상군, 경도인지장애군, 치매환자군 ) 다른군간의차이점을보정해주기위함이다. 이러한인자들은 student t-test를통한각군간의성별과나이를비교하여나타난결과를바탕으로선택되었다. 성별에서의차이는정상인 (CN) 과 MCI환자, 정상인과 AD환자사이에서통계적으로별차이가없었지만 (p > 0.05), MCI환자와 AD환자간에는유의한차이가있었다 (p < 0.05). 나이에따른차이에서는정상인 Fig. 7. Beta image volumes in a general linear model; The ages are the coefficients of the third order polynomial Maps from the second row to the sixth row represent beta image volumes in a general linear model of the standard templates caused by the co-varietiesof age, gender, and DDX. GM: Gray matter WM: White matter CSF: Cerebrospinal Fluid DDX: Differential diagnosis

29 김민지외 과 MCI환자에서는차이가거의없었지만 (p > 0.05) 정상인과 AD환자및 MCI환자와 AD환자간에는유의한차이가있었다 (p < 0.05) (Table1). 따라서우리의모델을평가하기위하여일반선형모델 (general linear model) 방정식을사용하여각복셀에대한 T1강조영상과회백질, 백질및뇌척수액의나이에따른 4개의인자와하나의성별및환자군간의차이에따른조직맵을얻었다 (Fig. 7). 다음으로생성 (creation) 단계를통해평가 (estimation) 된변화인자를이용하여공변량값을마찬가지로나이와성별로하여쌍일치접근 (matched pairs approach) 방법으로하여각각변수에대하여각조직맵을만들고한국노인및치매환자의뇌표준판을만들었다. 한국노인및치매환자의뇌표준판과 MNI152 뇌표준판의각기준점들간의평균거리를알기위해정의된8개의 Talairach 기준점 (Talairach reference point) 중에서본연구에서는 6개의기준점을선택하여각각의거리를수동적으로계산하였는데그결과로 AP-PP 거리에서 MNI152 뇌표준판은 mm, 한국노인의뇌표준판은 mm 이었고 RP-LP 거리는각각 131 mm, mm 이었으며 SP-IP 거리는각각 mm와 mm이었다 (Fig. 2). 또한 MNI 뇌표준판과한국노인및치매환자의뇌실의크기를알기위해 a부터 e까지의특정영역을선정하여각각에따른거리를수동적으로계산하였다. 그결과전반적으로두표준판에서뇌실의크기에따른차이가있었다 (Fig. 3). 두연구간에뇌표준판의크기 (template size) 가다르기때문에직접적인평균거리와뇌실의크기를비교하는데에는제한이있었다. 평균적으로이들표준뇌영상은현재 SPM5 프로그램에서사용하고있는 MNI152 뇌표준판의복셀크기 mm과비교하면한국노인및치매환자의뇌표준판의복셀크기는 mm로공간분해능 (spatial resolution) 이뛰어남을보여주었다. 회백질과백질의영역을조사하기위해서뇌전체영역에따른회백질과백질의확률이 50% 이상인복셀개수를세어계산하였다. 회백질의경우한국노인및치매환자의뇌표준판은 34.9% 이었고 MNI152뇌표준판은 54.9% 로본연구에서의뇌표준판이약 20% 적었고, 백질의경우각각 21.2% 와 23.4% 로본연구에서개발한뇌표준판이약2.2% 더적었다. 대체적으로본연구에서개발한뇌표준판의회백질과백질의영역이작았고, 백질보다회백질영역에서더많은차이가있었다. 비교한결과로보아연령간에차이와인종간의차이때문에발생한것으로판단된다. 이번연구에서제한점은피험자군간의성별과나이의차이가유의하게나타났는데뇌표준판을만드는과정에서성별, 나이별및환자군별에따른차이 (Differential diagnosis, DDX) 를고려하여만들어연구의단점을극복하였다고평가할수있다. 결 본연구는한국노인및치매환자들의뇌기능을분석하기위한삼차원T1강조영상을이용한복셀기반형태분석에서 SPM5 프로그램을이용해뇌표준판에공간정규화할경우분석오차를최소화하기위해서뇌구조영상의표준판을개발하는연구를시행하였다. 50~80대사이한국노인및치매환자에조직맵 ( 회백질, 백질및뇌척수액 ) 을분할한뒤, 평가 (estimation) 와생성 (creation) 과정을통해한국노인과치매환자의세분화된특정뇌표준판을완성하였다. 각기준점들간의평균거리와뇌실의거리를쟀을경우두표준판에유의미한차이가있었다. 그러나두연구간의뇌표준판과크기가다르기때문에크기를비교하는데는제한이있었다. 뇌전체영역에따른회백질및백질의영역를확률로계산하여비교한결과에서회백질과백질영역모두에서한국및치매환자의뇌표준판이더작았고, 백질의영역보다회백질에서더많은차이를보였다. 또한연구에맞는특별한대상으로개발한표준판이공간분해능과공간해상도가높음을보여주었다. 본연구에서개발한뇌표준판은앞으로한국노인과치매환자의질환을분석하는데에기여하고자한다. 나아가우리는 SPM5 프로그램을사용했는데현재까지 SPM8 프로그램이개발되어사용중에있고앞으로계속적인소프트웨어프로그램발전을통해더세밀한분할과평탄화, 운동물 (artifacts) 제거등을통한정확한분석과판단이가능해질것으로기대해본다. 론 참고문헌 1.Brant-Zawadzki, M, G.D. Gillan, and W.R. Nitz, MP RAGE: a three-dimensional, T1-weighted, gradient-echo sequence--initial experience in the brain. Radiology 1992;182: Yamashita E, et al. Evaluation of three-dimensional fast spoiled gradient recalled acquisition in the steady state (FSP- GR) using ultra magnetic field 3-Tesla MRI for optimal pulse sequences of T1-weighted imaging. Nippon Hoshasen Gijutsu Gakkai Zasshi 2006;62: Pruessner JC, et al. Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. Cereb Cortex 2000;10: Ashburner J. and K.J. Friston, Voxel-based morphometry--the methods. Neuroimage 2000;11: Evans AC, et al. Anatomical mapping of functional activation in stereotactic coordinate space. Neuroimage 1992;1: Braak, H. and E. Braak, Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991;82: Lim HK, Choi EH, and Lee CH, A voxel-based Morphometry of gray matter reduction in patients with dementia of the Alzheimer s type. Kor J Biol Psychia 2008;15: Kakeda, S. and Y. Korogi, The efficacy of a voxel-based mor

30 정상노인및경도인지장애및알츠하이머성치매환자에서의한국인뇌구조영상표준판개발 phometry on the analysis of imaging in schizophrenia, temporal lobe epilepsy, and Alzheimer s disease/mild cognitive impairment: a review. Neuroradiology, Frisoni GB, et al. The Clinical Use of Structural MRI in Alzheimer Disease. Nat Rev Neurol 2010;6: Choi SH, et al. Optimized VBM in patients with alzheimer s disease: gray matter loss and its correlation with cognitive function. J Kor Rad Soc 2005;53: Abe O, et al. Voxel-based analysis of the diffusion tensor. Neuroradiology, Jahng, GH and N. Schuff, Influence of selecting EPI readoutencoding bandwidths on arterial spin labeling perfusion MRI. MAGMA 2009;22: Schweinhardt P, et al. A template for spatial normalisation of MR images of the rat brain. J Neurosci Methods 2003;129: Tang S, et al. RABBIT: rapid alignment of brains by building intermediate templates. Neuroimage 2009;47: Kazemi K, et al. A neonatal atlas template for spatial normalization of whole-brain magnetic resonance images of newborns: preliminary results. Neuroimage 2007;37: Choi DY, et al. Development of Korean standard brain templates according to gender and age. The Korean J Aant 2004; 37: Lee JS, et al. Development of Korean standard brain templates. J Korean Med Sci 2005;20: Shin DH, et al. A study on the deviation of cluster based on template images of Korean children s brain SPECT image using the statistical parametic mapping. Kor Med Phys 2004; 15: Talairach, J. and P. Tournoux, Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system-an approach to cerebral imaging. Thieme Medical Publishers 1988: p Lancaster JL, et al. Bias between MNI and Talairach coordinates analyzed using the ICBM-152 brain template. Hum Brain Mapp 2007;28: Zilles, K, et al. Hemispheric shape of European and Japanese brains: 3-D MRI analysis of intersubject variability, ethnical, and gender differences. Neuroimage 2001;13: Chung SC, et al. The voumetric study of the ventricle in Korean according to age and gender. Kor J Anat 2005;38: May, A. and C. Gaser, Magnetic resonance-based morphometry: a window into structural plasticity of the brain. Curr Opin Neurol 2006;19: Wells WM, et al. Adaptive segmentation of MRI data. IEEE Trans Med Imaging 1996;15: Wilke M, et al. Template-O-Matic: a toolbox for creating customized pediatric templates. Neuroimage 2008;41: Franke K, et al. BrainAGE: a completely automated age estimation framework using structural MRI. 16th Annual Meeting of the Organization for Human Brain Mapping Barcelona, Spain 27.Karas G, et al. Precuneus atrophy in early-onset Alzheimer s disease: a morphometric structural MRI study. Neuroradiology 2007;49: Lee JS, et al. Development of Korean Standard Brain Templates. Kor Acad Med Sci 2005;20:

31 김민지외 J. Korean Soc. Magn. Reson. Med. 14: (2010) Development of a Korean Standard Structural Brain Template in Cognitive Normals and Patients with Mild Cognitive Impairment and Alzheimer s Disease Min-Ji Kim 1, 2, Geon-Ho Jahng 2, Hack-Young Lee 3, Sun-Mi Kim 2, Chang-Woo Ryu 2, Won-Chul Shin 3, Soo-Yeol Lee 1 1 Department of Biomedical Engineering, Kyunghee University, Youngin 2 Department of Radiology, Kyunghee University Hospital-Gangdong, School of Medicine, Kyunghee University, Seoul 3 Department of Neurology, Gangdong Kyunghee University Hospital-Gangdong, School of Medicine, Kyunghee University, Seoul Purpose : To generate a Korean specific brain template, especially in patients with Alzheimer s disease (AD) by optimizing the voxel-based analysis. Materials and Methods : Three-dimensional T1-weighted images were obtained from 123 subjects who were 43 cognitively normal subjects and patients with 44 mild cognitive impairment (MCI) and 36 AD. The template and the corresponding aprior maps were created by using the matched pairs approach with considering differences of age, gender and differential diagnosis (DDX). We measured several characteristics in both our and the MNI templates, including in the ventricle size. Also, the fractions of gray matter and white matter voxels normalized by the total intracranial were evaluated. Results : The high resolution template and the corresponding aprior maps of gray matter, white matter (WM) and CSF were created with the voxel-size of mm. Mean distance measures and the ventricle sizes differed between two templates. Our brain template had less gray matter and white matter areas than the MNI template. There were volume differences more in gray matter than in white matter. Conclusion : Gray matter and/or white matter integrity studies in populations of Korean elderly and patients with AD are needed to investigate with this template. Index words : Alzheimer s disease Brain template Voxel-based analysis Age Gender Address reprint requests to : Geon-Ho Jahng, Ph.D., Department of Radiology, Kyunghee University Hospital-Gangdong, School of Medicine, Kyung Hee University, 149 Sangil-dong, Gangdong-gu, Seoul , Korea. Tel Fax ghjahng@gmail.com

32 활성자극파라다임 fmri 에서저주파요동성분분석 나성민 1 박현정 2 장용민 1, 3 목적 : 활성자극파라다임을사용한기능적자기공명영상데이터에서자발적요동에해당하는저주파 BOLD 신호의존재여부를규명해보고자하였다. 대상및방법 : 20명의여자양궁선수들과양궁경험이없는 23명의여자들을대상으로 fingertapping 파라다임은 30초간의운동기와휴지기를 3회반복하였다. 혈액산소수준의존 (BOLD) fmri 영상은 3.0 T MR 기기에서경사자장반향 EPI 영상을해부학적영상은 3차원 T1 강조영상을사용하였다. 뇌활성화차이는 SPM-5를사용하여분석하였고저주파요동성분을찾기위해 GIFT 프로그램을사용하였다. 결과 : 두군모두에서 finger-tapping에따라대뇌좌측의주운동영역과보조운동영역그리고우측소뇌에서의활성화가관찰되었다. GIFT를사용한 ICA 분석에서피검자들의반측감각운동망, 동측감각운동망그리고인지기능과연관된신경망에해당하는독립적인성분들이구별되었다. 결론 : Finger-tapping fmri 데이터에서 BOLD 신호의자발적요동에해당하는저주파신호성분들을 ICA 기법을사용하여분리해낼수있었고이러한독립성분들이일차운동감각신경망그리고운동인지기능을담당하는신경망의휴지기신경활동을나타낸다는사실을규명할수있었다. 서론현재까지시행되고있는고식적인기능적자기공명영상 (functional magnetic resonance imaging: fmri) 기법은주로특정한활성자극 (active stimulation) 을주고자극에반응하는뇌영역을규명하는방법이대부분이다 (1, 2). 최근특정한자극이주어지지않은휴지상태 (resting-state) 에서도자발적으로요동하는혈액산소수준의존 (blood oxygen level dependent: BOLD) 신호가존재하며이러한 BOLD 신호의자발적요동 (spontaneous fluctuation) 은뇌대사의대부분을차지하는자발적신경활동 (spontaneous neuronal activity) 을반영하는것으로해석되고있다 (3-5). BOLD 신호의자발 적요동은매우낮은주파수영역에서일어나는것으로알려져있으며자발적요동성분을찾기위해서는활성자극이주어지지않은휴지상태에서 BOLD 신호를측정한후 0.01에서 0.1 Hz 영역의저주파신호를분리한후동일한양상 (pattern) 으로자발적요동을나타내는뇌영역을표시하게되는데이를휴지상태기능적자기공명영상 (resting-state fmri) 이라한다. 본연구에서는활성자극파라다임을사용한고식적인기능적자기공명영상데이터에서 BOLD 신호의자발적요동에해당하는저주파 BOLD 신호의존재여부를규명해보고자하였다. 고식적인기능적자기공명영상의자극상태에서발생하는저주파 BOLD 신호의규명은자극에대한뇌활성화영역과자극과상관없는자발적신경활동을구분할수있다는점에서매우중요한의미를가진다. 또한자극상태에서발생하는자발적신경활 대한자기공명의과학회지 14: (2010) 1 경북대학교대학원의용생체공학과 2 제주대학교수의과대학 3 경북대학교병원영상의학과본연구는보건복지가족부보건의료연구개발사업의지원에의해이루어진것임 (A092106) 접수 : 2010 년 11 월 1 일, 수정 : 2010 년 11 월 5 일, 채택 : 2010 년 11 월 8 일통신저자 : 장용민, ( ) 대구광역시중구삼덕동 50, 경북대학교병원영상의학과 Tel. (053) FAX. (053)

33 나성민외 동인저주파 BOLD 신호를나타내는뇌영역이전문가집단과대조군사이에차이를보이는지알아보기위해단순한감각운동 (sensorimotor) 활성자극파라다임인 finger-tapping 파라다임을사용하여저주파 BOLD 신호를나타내는뇌영역이양궁선수군과대조군사이에차이를보이는지알아보고자하였다. 대상및방법가. 대상 20명 ( 평균나이 : 28.9세 ) 의오른손잡이여자양궁선수들과대조군으로양궁경험이없는 23명 ( 평균나이 : 26.3세 ) 의오른손잡이여자들을대상으로하였다. 두군간나이차이는통계적으로유의하지않았다 (p=0.49). 선수군과대조군모두과거신경학적병력이없고현재뇌신경계에영향을미칠수있는약물을복용하지않는사람을대상으로하였다. 모든대상자는연구의목적과방법에대하여충분히이해하였으며자발적동의후, 실험에참가하였다. 나. 활성자극파라다임및기능적자기공명영상데이터획득대상자들은몸의움직임을최소화하기위해고정기구를사용하였다. finger-tapping 파라다임은운동기동안에오른손엄지를제외한네손가락을 첫번째손가락 (1)-세번째손가락 (3)- 두번째손가락 (2)-네번째손가락 (4) 의순서로반복적으로두드리는동작을시행하고휴지기동안에는동작을멈추었다. 30 초간의운동기와 30초간의휴지기를반복하였으며각각의운동기와휴지기는 3회반복하였으며총 3분이소요되었다. 혈액산소수준의존 (BOLD) fmri 영상은 3.0 T MR 기기 (VHi, GE healthcare, USA) 에서 8채널두부코일을사용하여경사자장반향 EPI 기법을적용하였다. 영상획득파라미터는 TR/TE= 2 sec/30 ms, FOV 220 mm, matrix 64 64, slice thickness 4 mm로하였으며모든영상은전교련과후교련을연결한선 (AC-PC line) 에평행이되도록경축면 (transaxial) 으로촬영하였다. 고해상도해부학적영상은 3차원 FSPGR T1 강조영상을사용하여획득하였다. 다. 기능적자기공명영상데이터분석 (1) 활성자극데이터분석 Finger-tapping에따른운동기와휴지기의뇌활성화차이는 MATLAB(Mathwork INC, Natick, MA, USA) 에서 SPM- 5 software (Wellcome Department of Cognitive Neurology, London, UK) 을이용해분석하였다. 기능적영상데이터는분석에앞서움직임을보정하기위해재정렬과 SPM 에서제공하는 Montreal Neurological Institute (MNI) 템플릿에맞추어규격화 (normalization) 하였다. 뇌활성화차이는일차적으로개별데이터를분석한후랜덤효과분석법을사용하여군별그룹분석을시행하였다. 또한다중 비교에따른 1종오류인 faluse positive error를보정하기위해 faluse discovery rate(fdr) 보정을시행하였으며통계적으로 p <0.05 (FDR corrected) 일때의미있게활성화된영역으로간주하였다. (2) 저주파요동성분분석기능적자기공명영상데이터로부터저주파요동성분을찾기위해 SPM에서제공하는 GIFT ( sourceforge.net) 프로그램을사용하였다. GIFT는사용자가주관적으로관심영역을설정하여분석하는 seed 분석법과달리영상데이터를통계적인의미로써최대한독립적인요소들을분리하는매우객관적인방법인독립요소분석 (Independent Component Analysis: ICA) 를사용하는장점이있다. GIFT 를사용한저주파요동성분분석역시앞서활성자극데이터분석에서처럼영상데이터의전처리과정을거친후 0.01에서 0.1 Hz대역의저주파 BOLD 신호를 ICA 분석법으로분석하였다. 일차적으로개별데이터를분석한후랜덤효과분석법을사용하여군별그룹분석을시행하였으며. 다중비교에따른오류를보정하기위해 faluse discovery rate(fdr) 보정을시행하였으며통계적으로 p <0.05 (FDR corrected) 일때의미있는저주파 BOLD 신호를나타내는영역으로간주하였다. 결과가. Finger-tapping 자극에따른뇌활성화영상양궁선수군및대조군모두에서오른손가락의 fingertapping에따라대뇌좌측의주운동영역 (primary motor area) 과보조운동영역 (supplemntal motor area) 그리고우측소뇌에서의활성화가관찰되었다 (Fig. 1). 두군모두에서대뇌우측주운동영역및 premotor 영역에서미약한활성화가추가적으로관찰되었다. 두표본 t 검증 (two sample t-test) 에서두군간차이는나타나지않았다. 나. 저주파요동성분영상 GIFT를사용한 ICA 분석에서오른손잡이인피검자들의반측 (contralateral) 감각운동망 (Fig. 2), 동측 (ipsilateral) 감각운동망 (Fig. 3) 그리고인지기능과연관된신경망 (Fig. 4) 에해당하는독립적인성분들이구별되었다. 반측및동측감각운동두표본 t 검증 (two sample t-test) 에서두군간차이는나타나지않았다. 고찰 Finger-tapping 자극은감각운동신경망을알아보는데매우보편적으로사용되고있는파라다임으로 Finger-tapping 자극에반응하여활성화된뇌영역들은다른연구자들에의해보고된영역들과유사한결과를나타내었는데오른손가락운동에대하

34 활성자극파라다임 fmri 에서저주파요동성분분석 여대뇌의반측감각운동신경망이주로활성화되는결과를보여주고있다 (6, 7). 또한숙련된운동집단인양궁선수군과대조군에서활성화영역들에차이가없었다는결과는 Fingertapping과같은단순운동에대해서는훈련된운동선수들이나일반인모두동일한뇌영역을사용한다는사실을보여주고있다. 운동기와휴지기를반복하는 Finger-tapping 파라다임수행동안획득된영상데이터의 0.01에서 0.1 Hz대역의저주파 BOLD 신호를 ICA 분석법으로분석한결과몇개의의미있는독립성분들을분리해낼수있었다. 첫째대뇌반측및동측감각운동망에해당하는독립성분들이분리되었는데이는대뇌반측 및동측감각운동망이서로기능적으로연결성 (connectivity) 을가지는것으로해석할수있다. 해부학적그리고기능적으로대뇌좌우반구의감각운동신경망이서로연결되어있다는사실은과거많은연구를통해잘알려져있다 (8, 9). Fingertapping 자극에반응하여활성화된뇌영역들과자발적저주파 BOLD 신호를통해획득한감각운동망사이의일치는감각운동신경망이 Finger-tapping과같은능동적인운동을시행하지않는경우에도감각운동망을형성하는대뇌구조물사이에자발적 (spontaneous) 이고서로밀착된 (coherent) 저주파요동성분의신호를형성하고있다는사실을시사한다. 즉, 운동을하 Fig. 1. One sample t-test group activation map for active finger-tapping task (FDR corrected p<0.01). Fig. 2. Group map of ICA component-1 represents contralateral sensorimotor network for dominant right hand (FDR corrected p<0.01)

35 나성민외 지않는휴지상태에서도대뇌감각운동망은자발적신경활동을하고있음을의미하는것으로해석할수있다. 본연구결과의중요한또다른시사점은휴지상태에서뇌가사용하는대사소모량에비해자극에따른활성화는 5% 미만의증가를보인다는연구결과에비추어볼때 Finger-tapping 자극에반응하여활성화된뇌영역의대사 (metabolism) 증가는휴지상태에서대뇌감각운동망의자발적신경활동에사용되는대사량과비교하는경우매우미약한증가라는점이다. 또한양궁선수군과대조군에서대뇌반측및동측감각운동망에해당하는독립성분들에차이를보이지않았다는결과는대조군에비해많은훈련을거친운동전문가집단이나대조군모두에서휴지상태에서대뇌감각운동망의자발적신경활동에는차이가없다는사실을시사한다. 즉, Finger-tapping과같이일상적으로반복되는매우단순한운동에대한대뇌감각운동망의자발적신경활동은훈련에의해변화하지않는것으로해석할수있다. 그러나피아노연주자와같이 Finger-tapping과연관된훈련과정을반복한전문가집단에서도훈련에의해대뇌감각운동망의자발적신경활동이변화하지않는지여부는추후연구를통해규명하여야할것으로판단된다. ICA 분석결과서로밀착된저주파 BOLD 신호를나타내는또다른독립성분으로는전운동영역 (premotor area), 전보조운동영역 (pre-sma), 배외측전전두피질 (dorsolateral prefrontal cortex), 왼쪽복외측전전두피질 (ventrolateral prefrontal cortex) 로구성된신경망이있다. 전운동영역은움 직임의감각적유도 (sensory guidance) 을주관하는뇌영역으로알려져있는데 Finger-tapping 운동시손가락으로고정판을두드리는과정에서고정판과손가락의접촉에의한감각을감지하여손가락이적절하게고정판을두드리게하는역할을담당하는것으로판단된다 (10). 전보조운동영역은새로운운동순서 (sequence) 를학습하는과정에서중요한역할을하는구조물로알려져있다 (11, 12). 본연구에서사용한 Fingertapping 파라다임은운동기동안에오른손엄지를제외한네손가락을 의순서로반복적으로두드리는동작을시행하게하였으므로대부분의피검자들이이러한일련의운동순서를학습하는것과연관된것으로판단된다. 배외측전전두피질은운동계획 (motor planning), 구성, 규제등운동의인지적기능에중요한역할을담당한다 (13). 즉, Finger-tapping 운동시네손가락을 의순서로반복적으로두드리는동작을계획하고운동순서를구성하며계획된순서를제대로시행하는지모니터링하는과정을담당하는것으로판단된다. 최근의연구결과에따르면왼쪽복외측전전두피질은기억조절 (memory control) 과매우밀접한연관성을가진다는사실이보고되었다 (14). 본연구에서는네손가락을 의순서로반복적으로두드리는동작을기억하여조절하는것과연관되어자발적인신경활동을보이는것으로판단된다. 전운동영역, 전보조운동영역, 배외측전전두피질, 왼쪽복외측전전두피질로구성된신경망은앞서의감각운동신경망이일차운동감각 (primary sensorimotor) 신경망을구성하는대뇌구조물간의 Fig. 3. Group map of ICA component-2 represents ipsilateral sensorimotor network for dominant right hand (FDR corrected p<0.01)

36 활성자극파라다임 fmri 에서저주파요동성분분석 Fig. 4. Group map of ICA component-3 represents cognitive network for dominant right hand (FDR corrected p<0.01). 자발적이고서로밀착된요동을나타내는것과비교하여 Finger-tapping 운동의학습, 계획, 순서기억및모니터링과같은인지기능을담당하는신경망구조물사이의자발적이고서로밀착된요동을나타내는것으로해석할수있다. 본연구의제한점으로는호흡및심장박동에따른저주파잡음을별도로제거하지않았다는점이다. 호흡이나심장박동주기에의해발생하는저주파잡음은저주파의자발적요동신호에영향을미칠수있으나여러보고에따르면저주파의자발적요동신호는호흡이나심장박동주기에의해발생하는저주파잡음신호와는주파수특성과양상이매우다르다고알려져있다 (15, 16). 하지만호흡이나심장박동과같은생리적인저주파잡음은저주파의자발적요동신호를분리해낼때주요잡음으로작용하여신호대잡음비 (singal-to-noise ratio) 를떨어뜨릴가능성이있으므로동기화 (gating) 기법등을사용하여가능한이러한잡음원인을제거하는것이필요할것이다. 결론본연구에서는활성자극파라다임인 Finger-tapping 기능적자기공명영상데이터에서 BOLD 신호의자발적요동에해당하는저주파 BOLD 신호성분들을 ICA 기법을사용하여분리해낼수있었고이러한독립성분들이일차운동감각신경망그리고운동의학습, 계획, 순서기억및모니터링과같은인지기능을담당하는신경망의자발적이고서로밀착된신경활동을나타낸 다는사실을규명할수있었다. 참고문헌 1.Bandettini PA, Wong EC, Hinks RS, Tikofsky RS, Hyde JS. Time course EPI of human brain-function during task activation. Magn Reson Med 1992;25: Ogawa S, Tank DW, Menon R, et al. Intrinsic signal changes accompanying sensory stimulation-functional brain mapping with magnetic-resonance-imaging. Proc Natl Acad Sci USA 1992;89: Attwell D, Laughlin SB. An energy budget for signalling in the grey matter of the brain. J Cereb Blood Flow Metab 2001;21: Ames AI. CNS energy metabolism as related to function. Brain Res Rev 2000;34: Raichle ME, Mintun MA. Brain work and brain imaging. Annu Rev Neurosci 2006;29: Indovina I, Sanes JN. Combined visual attention and finger movement effects on human brain representations. Exp Brain Res 2001;140: Sadato N, Campbell G, Ibán ez V, Deiber M, Hallett M. Complexity affects regional cerebral blood flow change during sequential finger movements. J Neurosci 1996;16: Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain. Magn Reson Med 1995;34: Mayka MA, Corcos DM, Leurgans SE, Vaillancourt DE. Three

37 나성민외 dimensional locations and boundaries of motor and premotor cortices as defined by functional brain imaging: a metaanalysis. Neuroimage 2006;31: Mushiake H, Inase M, Tanji J. Neuronal activity in the primate premotor, supplementary, and precentral motor cortex during visually guided and internally determined sequential movements. J Neurophysiol 1991;66: Cunnington R,Windischberger C, Deecke L, Moser E. The preparation and execution of self-initiated and externally-triggered movement: a study of event-related fmri. Neuroimage 2002;15: Deiber MP, Honda M, Ibanez V, Sadato N, Hallett M. Mesial motor areas in self-initiated versus externally triggered movements examined with fmri: effect of movement type and rate. J Neurophysiol 1999;81: Jenkins IH, Jahanshahi M, Jueptner M, Passingham RE, and Brooks DJ. Self-initiated versus externally triggered movements. II. The effect of movement predictability on regional cerebral blood flow. Brain 2000;123: Badre D, Wagner AD. Left ventrolateral prefrontal cortex and the cognitive control of memory. Neuropsychologia 2007; 45(13): Birn RM, Diamond JB, Smith MA, Bandettini PA. Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fmri. Neuroimage 2006;15: Shmueli K, van Gelderen P, de Zwart JA, et al. Low-frequency fluctuations in the cardiac rate as a source of variance in the resting-state fmri BOLD signal. Neuroimage 2007;38: J. Korean Soc. Magn. Reson. Med. 14: (2010) Low Frequency Fluctuation Component Analysis in Active Stimulation fmri Paradigm Sung-Min Na 1, Hyun-Jung Park 2, Yongmin Chang 1, 3 1 Department of Medical and Biological Engineering, Kyungpook National University 2 Jeju National University College of Veterinary Medicine 3 Department of Radiology, Kyungpook National University Hospital Purpose : To separate and evaluate the low frequency spontaneous fluctuation BOLD signals from the functional magnetic resonance imaging data using sensorimotor active task. Materials and Methods : Twenty female archery players and twenty three control subjects were included in this study. Finger-tapping task consisted of three cycles of right finger tapping, with a subsequent 30 second rest. Blood oxygenation level-dependent (BOLD) data were collected using T2*-weighted echo planar imaging at a 3.0 T scanner. A 3-D FSPGR T1-weighted images were used for structural reference. Image processing and statistical analyses were performed using SPM5 for active finger-tapping task and GIFT program was used for statistical analyses of low frequency spontaneous fluctuation BOLD signal. Results : Both groups showed the activation in the left primary motor cortex and supplemental motor area and in the right cerebellum for right finger-tapping task. ICA analysis using GIFT revealed independent components corresponding to contralateral and ipsilateral sensorimotor network and cognitive-related neural network. Conclusion : The current study demonstrated that the low frequency spontaneous fluctuation BOLD signals can be separated from the fmri data using finger tapping paradigm. Also, it was found that these independent components correspond to spontaneous and coherent neural activity in the primary sensorimotor network and in the motor-cognitive network. Index words : fmri, Active paradigm, Spontaneous fluctuation, ICA Address reprint requests to : Yongmin Chang, Ph.D., Department of Radiology, Kyungpook National University Hospital, Sam-duk-dong, 2ga 50, Daegu , Korea. Tel Fax

38 유방암환자에서추가병변평가를위한 3 테슬러유방자기공명영상의임상적경험 이지혜 1 김성헌 1 강봉주 1 최재정 1 이아원 2 목적 : 본연구는유방암진단후추가적으로유방암을발견하는데있어 3 테슬러유방자기공명영상의진단적정확성을알아보고자하였다. 대상및방법 : 2009년 3월부터 6월까지, 새롭게유방암을진단받은 101명의환자가유방자기공명영상을촬영하고수술을받았다. 자기공명영상에서는종양의범위와다초점, 다중심, 반대측유방암이의심되는소견에대해분석하였다. 자기공명영상으로발견된유방암은조직검사나위치결정술후수술로진단되었다. 결과 : 34명환자에서 37예의암이의심되는소견이추가적으로자기공명영상에서보였다. 16 예의다초점유방암, 11예의다중심유방암그리고 2예의반대측유방암을포함하여 29예가진양성이었다 (29/37, 78.4%); 13 (44.8%) 예는관내상피암그리고 16 (55.1%) 예는침윤성암이었다. 6예의양성병변, 2예의고위험병변을포함하여 8예가위양성이었다 (8/37, 21.6%). 결론 : 3 테슬러자기공명영상에서최근에유방암이진단된환자의 33.7% 에서추가적으로암이의심되는소견이보였다. 추가적으로유방암을발견하는 3 테슬러자기공명영상의민감도와특이도는각각 100%, 89.3% 였다. 서론역동성조영증강자기공명영상은유방암의발견, 진단및병기결정에있어민감도가높은우수한영상검사로알려져있다하지만, 높은민감도에비해특이도가낮은제한점이있고이로인해불필요한조직검사, 환자의불안, 의료비지출을유발할수있다 (1-3). 임상에서고자장 (3 테슬러 ) 자기공명영상의사용이증가하고있으며, 이는 3 테슬러자기공명영상의높은신호대잡음비율로인해높은공간해상능과시간해상능을얻을수있어조영증강과정확한병변의평가를통해유방암발견을향상시킬수있기때문이다 (2, 4, 5). 3 테슬러자기공명영상을 1 테슬러, 1.5 테슬러자기공명영상과비교한연구에서, 3 테슬러자기공명영상이유방암발견에있어더높은민감도를 보였고, 비슷한특이도를보였다고발표하였다 (1). 본연구는 3 테슬러유방자기공명영상의임상경험을보고하고유방암진단후추가적유방암발견을위한 3 테슬러유방자기공명영상의진단적정확성을알아보고자하였다. 대상및방법 2009년 3월부터 6월까지, 125명의환자가 3 테슬러유방자기공명영상을촬영하였다. 유방암검진을위한간질유방성형술 (interstitial mammoplasty) 환자 3명, 항암치료를받기로예정되었거나받은후추적검사를시행한 8명, 유방절제술후암이진단된환자 4명, 유방암수술후추적검사를시행한환자 9명을제외하였다. 새롭게유방암이진단되고수술을시행했던총 101명의환자가이연구에포함되었다. 환자의평균연령 대한자기공명의과학회지 14: (2010) 1 가톨릭대학교의과대학영상의학과 2 가톨릭대학교의과대학병원병리학과접수 : 2010 년 6 월 9 일, 수정 : 2010 년 9 월 15 일, 채택 : 2010 년 11 월 17 일통신저자 : 김성헌, ( ) 서울시서초구반포동 505 번지, 가톨릭의과대학영상의학과 Tel. (02) Fax. (02) rad-ksh@catholic.ac.kr

39 이지혜외 은 51.2 세였고연령분포는 35세에서 75세였다. 자기공명영상검사는 3T Magnetom Verio (Siemens Medical Solutions, Erlangen, Germany) 과유방전용코일을사용하였다. 사용된영상기법은다음과같다 ; 축상 turbo spin-echo T2-weighted imaging sequence (TR/TE= 4530/93, a flip angle of 80, 34 slices with FOV (320 mm), matrix ( ), 1 NEX and 4 mm slice thickness, acquisition time of 2 minutes 28 seconds); 조영증강전과조영증강후축상 T1-weighted flash threedimensional, VIBE sequence (TR/TE=4.4/1.7, flip angle 10, 1.2 mm slice thickness, acquisition time of 7 minutes 7 seconds) 는 Gd-DPTA (Magnevist, Schering, Berlin, Germany) 주입전과주입후 7, 67, 127, 187, 247 그리고 367초에얻었다. 조직학적으로악성이확인된병변외에자기공명영상을통해서만추가적으로보이는악성이의심되는병변을분석하여자기공명영상의정확성을알아보았다. 두명의영상의학과의사가자기공명영상을후향적으로분석하였다. 자기공명영상에서악성이의심되는소견은다음과같이정의하였다 (6, 7); 침상또는불규칙한경계를갖고불균일하거나환상조영증강을보이는종괴, 관상 (ductal), 구역상 (segmental) 또는국소성 (regional) 분포를보이는비종괴양병변 (non mass-like lesion), 그리고지연시유실형 (washout) 조영증강을보이는종괴혹은종괴양병변. 유방촬영상에서보이지않을때, 초음파에서보이지않거나양성병변 ( 범주 2, 양성소견또는범주 3, 양성추정소견 ) 으로보였지만, 자기공명영상에서악성이의심되는소견이추가적으로보일때를자기공명영상양성소견 (positive finding) 으로보았다. 이병변에대해서는초음파를다시시행하여초음파유도하조직검사또는위치결정술후수술적조직검사를시행했고, 초음파에서뚜렷하지않을경우는수술검체를통하여확인하였다. 자기공명영상으로추가적으로발견된악성이의심되는병변은이미조직검사를시행한지표종양 (index tumor) 을기준으 로같은사분역 (quadrant) 에있을때는다초점성, 다른사분역에있을때는다중심성, 다른쪽유방에있는때는반대측병변으로분류하였다. 결 34명환자에서 37예의암이의심되는소견이추가적으로자기공명영상에서보였다 (Table 1). 17예는종괴로, 20예는비종괴양병변으로보였다. 종괴의평균크기는 0.9 cm( 크기분포 cm) 이었고비종괴양병변의평균크기는 1.8 cm( 크기분포 cm) 이었다. 침상또는불규칙한경계를갖고불균일하거나환상조영증강을보이는종괴는 12예, 관상 (ductal), 구역상 (segmental) 또는국소성 (regional) 분포를보이는비종괴양병변 (non mass-like lesion) 은 20예, 그리고지연시유실형 (washout) 조영증강을보이는종괴혹은종괴양병변은역동조영증강그래프의분석이가능한 32예중 19예였다. 추가적으로자기공명영상에서보인병변들은처음시행한초 Fig year-old woman with invasive ductal cancer and true positive multifocal malignancies. 3D MIP image shows an index mass (arrow) and two multifocal daughter nodules (arrowheads) at upper outer quadrant of right breast. 과 Table 1. Additional Suspicious Lesions on 3.0 T MRI True Positivity False Positivity Multifocality (n=20) 16 4 Multicentricity (n=14) 11 3 Bilaterality (n=3) 2 1 Total 29/37 (78.4%) 8/37 (21.6%) Histology DCIS (n=13) fibrocystic disease (n=3), invasive cancer (n=16) sclerosing adenosis ( n=2) fibroadenoma (n=1) atypical ductal hyperplasia (n=1) lobular carcinoma in situ (n=1) Note.-DCIS indicates ductal carcinoma in situ

40 유방암환자에서추가병변평가를위한 3 테슬러유방자기공명영상의임상적경험 음파에서양성으로여겨졌던병변이 14개, 처음시행한초음파에서는발견하지못했지만초음파를다시시행했을때보였던병변이 13개, 다시시행한초음파에서도뚜렷하지않았던병변은 10개였다. 후향적으로유방촬영술을다시보았을때 4예에서희미한악성이의심되는석회부위가, 1예에서구조왜곡이발견되었다. 16예의다초점유방암 (Fig. 1), 11예의다중심유방암 (Fig. 2) 그리고 2예의반대측유방암 (Fig. 3) 을포함하여 29예가진양성이었다 (29/37, 78.4%). 13예 (44.8%) 가관내상피암그리고 16예 (55.1%) 는침윤성암이었다. 16명환자에서동측유방암이, 2명환자에서반대측유방암이발견되었다. 8예는위양성이었다 (8/37, 21.6%). 섬유낭성질환 (3예), 경화샘증 (2예), 섬유선종 (1예) 를포함하여 6예가양성병변이었고비정형관증식증과상피내소엽성암종각1예씩 2예가고위험병변이었다. 추가적으로유방암을발견하는 3 테슬러자기공명영상의민감도와특이도는각각 100%, 89.3% 였다. 67명의환자는 3 테슬러자기공명영상에서지표종양외에추가적으로암이의심되는소견이없었다. 6명을제외한 61명의환자가평균 12개월 (6개월-15개월) 의추적기간내에유방초음파와유방촬영술의추적영상검사를시행하였고조직검사가필요한악성의심소견은보이지않았다. 고 찰 Fig year-old woman with invasive ductal cancer and true positive multicentric malignancies. Axial subtraction image shows an index mass (arrow) at upper inner quadrant of left breast. Also detected multifocal and multicentric malignancies (arrowheads) are noted at left upper breast. Fig year-old woman with invasive ductal cancer and true positive contralateral malignancy. Axial subtraction image shows an index mass at right breast and an irregular spiculated homogeneously enhancing mass at left breast. 유방자기공명영상은높은민감도로인해유방암환자에서유방촬영술에서보이지않는다초점, 다중심유방암을추가적로발견할수있고, 고위험군에서치밀유방일경우유방암을발견할수있고수술전항암치료의반응을평가할수있는우수한검사방법이다. 하지만, 특이도가높지않은제한점이있다 (1-3). 또한유방암이의심되는병변의확진을위해중심코어생검등의조직검사를대체할수없다. 따라서자기공명영상의임상적으로가치있는발전은특이도를증가시켜양성병변을구별하여불필요한조직검사를줄이는방향으로이루어진다 (8). 3 테슬러자기공명영상은 1.5 테슬러자기공명영상에비해신호대잡음비율이더높아서정해진시간에높은공간대조능의영상을제공한다. 따라서보다정확한병변의형태학적분류를가능하게하여특이도를증가시킬수있다 (8). Kuhl 등은 37명, 53예의병변에대하여 1.5 테슬러와 3 테슬러자기공명영상을동시에얻어비교하였다. 78% 만이같은 BI-RADS 범주에속하였고 11개의병변은다른범주로분류되었는데, 병리결과를참고할때 3 테슬러영상이병변의분석과범주결정에우수하였다. 또한 1.5 테슬러영상은 4예에서섬유선종과동반된격막을구별하여보여주지못했지만, 3 테슬러영상에서는뚜렷하게잘보여주어범주 2, 양성소견을줄수있었다 (9). 1 또는 1.5 테슬러자기공명영상의민감도는 71% 에서 100% 까지, 특이도는 73.7% 에서 98% 까지보고되었다 (1, 3, 10-12). 3 테슬러자기공명영상의진단적정확도에대한연구는많지않다. 이중한연구는 434명의유방암의고위험군을대상으로 3 테슬러자기공명영상을촬영하였고 3 테슬러자기공명영상의민감도는 100%, 특이도는 93.9% 라고보고하였다 (1). 또다른연구는유방촬영술, 초음파검사가병변의평가에불충분할때, 유방암환자의수술전병기결정을위해, 유방암수술후추적검사를위해, 고위험군의검진목적으로 54명의환자에대해 3 테슬러자기공명영상을시행하였고민감도는 100%, 특이도는 74% 로보고하였다. 3차원최대강도투사재건영상 (3D maximal intensity projection reconstruction image) 을통

41 이지혜외 해혈관분포지도 (vascular map) 을얻어추가적으로병변평가에적용했을때특이도가 87% 까지증가했다고보고하였다 (8). 이전연구들의문헌을비교할때, 3 테슬러자기공명영상의민감도는 1 또는 1.5 테슬러자기공명영상보다우수하나특이도는비슷한정도임을알수있다. 최근에유방암을진단받은환자에서추가적인암발견의 3 테슬러자기공명영상의정확도를연구한본연구결과는민감도 100%, 특이도 89.3% 였으며이전결과들과비슷하였다. 본연구는적은수의환자를대상으로한후향적검사라는제한점이있었다. 또한자기공명영상에서악성이의심되는경우자기공명영상유도하위치결정술이나자기공명영상유도하조직검사를시행하지못하고초음파유도하조직검사를시행하거나병리조직검사를참고하였다. 따라서병리결과가자기공명영상의양성소견을직접적으로반영하지못하였다. 결론적으로, 3 테슬러자기공명영상에서최근에유방암이진단된환자의 33.7% 에서추가적으로암이의심되는소견이보였다. 추가적으로유방암을발견하는 3 테슬러자기공명영상민감도와특이도는각각 100%, 89.3% 였다. 참고문헌 1.Elsamaloty H, Elzawawi MS, Mohammad S, Herial N. Increasing accuracy of detection of breast cancer with 3-T M- RI. AJR Am J Roentgenol 2009;192: Orel SG, Schnall MD. MR imaging of the breast for the detection, diagnosis, and staging of breast cancer. Radiology 2001;220: Riedl CC, Ponhold L, Flory D, et al. Magnetic resonance imaging of the breast improves detection of invasive cancer, preinvasive cancer, and premalignant lesions during surveillance of women at high risk for breast cancer. Clin Cancer Res 2007;13: Kuhl CK. Breast MR imaging at 3T. Magn Reson Imaging Clin N Am 2007;15: Sasaki M, Shibata E, Kanbara Y, Ehara S. Enhancement effects and relaxivities of gadolinium-dtpa at 1.5 versus 3 Tesla: a phantom study. Magn Reson Med Sci 2005;4: Liberman L, Morris EA, Dershaw DD, Abramson AF, Tan LK. MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. AJR Am J Roentgenol 2003;180: Mameri CS, Kemp C, Goldman SM, Sobral LA, Ajzen S. Impact of breast MRI on surgical treatment, axillary approach, and systemic therapy for breast cancer. Breast J 2008;14: Schmitz AC, Peters NH, Veldhuis WB, et al. Contrast-enhanced 3.0-T breast MRI for characterization of breast lesions: increased specificity by using vascular maps. Eur Radiol 2008;18: Kuhl CK, Jost P, Morakkabati N, Zivanovic O, Schild HH, Gieseke J. Contrast-enhanced MR imaging of the breast at 3.0 and 1.5 T in the same patients: initial experience. Radiology 2006;239: Wiener JI, Schilling KJ, Adami C, Obuchowski NA. Assessment of suspected breast cancer by MRI: a prospective clinical trial using a combined kinetic and morphologic analysis. AJR Am J Roentgenol 2005;184: Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 2004;351: Leach MO, Boggis CR, Dixon AK, et al. Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet 2005;365:

42 유방암환자에서추가병변평가를위한 3 테슬러유방자기공명영상의임상적경험 J. Korean Soc. Magn. Reson. Med. 14: (2010) Clinical Experience of 3T Breast MRI in Detecting the Additional Lesions in Breast Cancer Patients Ji Hye Lee 1, Sung Hun Kim 1, Bong Joo Kang 1, Jae Jeong Choi 1, Ah Won Lee 2 1 Department of Radiology, College of Medicine, The Catholic University of Korea 2 Department of Hospital Pathology, College of Medicine, The Catholic University of Korea Purpose : The purpose of this study was to evaluate the diagnostic accuracy of 3.0-T breast MRI for detecting additional breast cancer soon after the initial diagnosis of breast cancer. Materials and Methods : From March to June 2009, 101 patients recently diagnosed breast cancer underwent breast MRI and surgery. Parameters analyzed on MRI were total extent of tumor, suspicious findings of multifocal, multicentric, or contralateral cancer. The diagnosis of MRI-detected cancer was confirmed by means of biopsy or surgical specimen evaluation after the localization. Results : MRI showed 37 additional suspicious findings in 34 patients. Twenty nine findings were truepositive (29/37, 78.4%), including 16 cases of multifocality, 11 cases of multicentricity and 2 cases of contralateral cancer. Among these cancers, 13 (44.8%) were ductal carcinoma in situ (DCIS) and 16 (55.1%) were infiltrating cancer. Eight findings were false-positive (8/37, 21.6%) including 6 cases of benign disease and 2 cases of high-risk lesions. Conclusion : In women with recently diagnosed breast cancer, 3.0-T MR imaging showed additional suspicious findings in 33.7%. The sensitivity and specificity for detecting additional breast cancer was 100% and 89.3%, respectively. Index words : Magnetic resonance imaging 3.0 Tesla Breast Breast cancer Address reprint requests to : Sung Hun Kim, M.D., Departement of Radiology, The Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul , Korea. Tel Fax rad-ksh@catholic.ac.kr

43 뇌피질이형성증의 3 차원뇌표면연출영상 황승배 곽효성 이상용 진공용 한영민 정경호 목적 : 뇌피질이형성증에서 3차원뇌표면연출영상의유용성을평가하고자하였다. 대상및방법 : 19명의국소적뇌피질이형성증을대상으로 MP-RAGE영상을이용하여 3차원뇌표면연출영상을얻었다. 비정상적인뇌이랑과뇌고랑의해부학적위치, 침범부위의뇌이랑과뇌고랑의형태와모양을평가하였다. 결과 : 비정상적인뇌이랑과뇌고랑의모양은 19명중 18명의환자에서관찰되었다. 병변부위의뇌이랑과뇌고랑의형태와배열, 침범모양은뇌표면연출영상에서명확하게평가되었다. 무뇌회증에서는엽이구분되지않았고, 뇌고랑이없고두껍고매끄러운뇌이랑이하나의엽으로되어있었다. 분열뇌증에서는분열틈을중심으로여러뇌이랑이바퀴모양을형성하고, 넓은뇌이랑을가지고있었다. 일측성거대뇌증에서는병변측대뇌반구가커져있었고, 두껍고넓은뇌이랑을가지고있었다. 선천성양측실비안주위증후군에서는섬피질이노출되어있었고, 병변부위의뇌이랑은두꺼워져있었다. 국소적뇌피질이형성증에서는균일하지않은톱니모양이나두껍고커진뇌이랑이보였다. 이중피질증후군에서는뇌이랑과뇌고랑의이상소견은보이지않았다. 결론 : 뇌피질이형성증환자에서 3차원뇌표면연출영상은비정상적인뇌피질의뇌이랑과뇌고랑의모양을평가할수있고정확한병변의위치를평가하는데유용하다. 뇌표면연출영상은수술전계획을세우는데유용한정보를제공한다. 서론간질은전국민의 0.5~1% 정도의유병률을가진흔한신경질환중하나이다. 치료약제의개발덕분에간질환자의경련을조절하는데많은발전이되었지만, 이중 25~30% 정도는약물치료로조절되지않는다 (1). 뇌피질이형성증 (cortical dysplasia) 은태생기초에시작되는신경이주이상 (neuronal migration disorder) 으로약물치료로조절이어려운경련성질환의주된원인이다 (2, 3). 경련성질환의원인으로뇌의국한된부위에병소가제한되어있을때수술적인치료방법이적용되기때문에 2차원적인뇌의이상소견뿐만아니라 3차원적인뇌표면의침범부위와모양 그리고주위정상적인뇌부위와해부학적인관계를파악하는것이필요하다. 측두엽성간질보다뇌피질이형성증에의한간질이수술후완치율이낮아서수술이전에원인이되는병변의정확한위치및모양, 그리고운동감각중추, 언어중추, 시각중추등뇌의중요부위와상세한공간적인관계를정확히확인해야한다 (4-7). 자기공명영상 (MRI) 은뇌의이상소견을발견하는데가장효과적인영상기법이다. 신경이주이상은뇌회질과백질사이의모양이나뇌회질의비정상적인신호강도와두께를 2차원적인영상으로평가해왔다 (8, 9). 그러나 2차원뇌영상으로는신경이주이상환자에서병변이침범된뇌표면의 3차원적인소견즉뇌이랑 (gyri) 이나뇌고랑 (sulci) 에대한형태학적소견은알기가어렵다. 최근 3차원자기공명영상에의해얻은정보로뇌표 대한자기공명의과학회지 14: (2010) 전북대학교의학전문대학원영상의학과 This paper was supported by funds from Chonbuk National University Hospital Research Institute. 접수 : 2010 년 8 월 13 일, 수정 : 2010 년 9 월 20 일, 채택 : 2010 년 11 월 17 일통신저자 : 정경호, ( ) 전주시덕진구금암동 , 전북대학교의학전문대학원영상의학과 Tel. (063) Fax. (063) chunggh@chonbuk.ac.kr

44 뇌피질이형성증의 3 차원뇌표면연출영상 면의재구성영상이가능해졌으며운동, 감각과언어중추영역과병변과의연관성을수술전에확인할수있어수술전치료계획에큰도움이될수있다 (10, 11). 이에저자들은 2차원자기공명영상에서뇌피질이형성증으로진단된환자에서 3차원표면연출영상 (surface rendering imaging) 을만들어뇌피질이형성증의 3차원해부학적위치를발견할수있는지그리고병변부위의뇌표면의뇌이랑과뇌고랑의두께와형태를파악하고주위정상부위와관련성을잘파악할수있는지를알아보고자하였다. 대상및방법신경이주이상인뇌피질이형성증환자 19명을대상으로하였으며남자 11명과여자 8명이었고평균연령은 26.6세 ( 연령범위, 1-50세 ) 이었다. 병변은 2명의뇌신경계를전문으로하는영상의학과의사가전형적인 2차원자기공명영상소견을중심으로무뇌회증 (lissencephaly) 2명, 분열뇌증 (schizencephaly) 4명, 일측성거대뇌증 (hemimegalencephaly) 2명, 선천성양측실비안주위증후군 (congenital bilateral perisylvian syndrome) 2명, 이중피질증후군 (double cortex syndrome) 1명, 그리고국소적뇌피질이형성증 (focal cortical dysplasia) 8명으로진단하였고, 이중 4명에서는수술을시행하여병리학적으로확진되었다. 뇌자기공명영상은 1.5T의 MRI기기 (Symphony, Siemens, Erlangen, Germany) 로시행하였으며, T1강조영상과 T2강조영상을 5 mm 두께로얻었고, 3차원표면연출영상을얻기위해 MP-RAGE(magnetization prepared papid gradient echo) 기법을이용하여 T1강조관상면영상을얻었다. MP- RAGE 영상의 parameter는 TE 4.0 msec, TR 9.7 msec, flip angle 12, matrix , slice thickness 1 mm(coronal slab, 256 mm thick, with 256 partitions), field of view , inplane resolution mm, 영상획득시간 11.56분이었다. 각각의얻은영상은 Marosis 5 를통해 Dicom형태로 VoxelPlus software (Mevisys, Daejeon, Korea) 로전송하여 3D plus 기능을이용하여뇌의뇌이랑과뇌고랑이가장잘보이는영상조건으로 3차원표면연출영상을시행하였고기본적으로각영상을 15 간격으로좌우, 그리고상하로돌려가면서저장하였으며그외의방향은 3 차원영상을여러각도로돌려가면서가장병변이잘보이는면을중심으로저장하였다. 모든환자에서고식적인 MR 영상소견과 3차원표면연출영상을 2명의뇌신경계를전문으로하는영상의학과의사가양측뇌이랑과뇌고랑의해부학적위치와비정상적인뇌이랑과뇌고랑의형태를관찰하였다. 결과 MP-RAGE T1강조영상을이용한 3차원표면연출영상의영 상획득시간은약 15분정도소요되었다. 3차원표면연출영상에서는전두엽, 두정엽, 그리고측두엽의중요한정상적인뇌이랑과뇌고랑의형태를파악할수있었다. 2D MR 영상에서는평가되지않았던병변의뇌이랑과뇌고랑의모양을정확하게평가할수있었고주위정상뇌이랑과뇌고랑의관계를 2D MR 영상보다잘평가할수있었다 (Fig. 1). 3차원표면연출영상에서이중피질증후군을제외한 18예에서비정상적인뇌이랑과뇌고랑의윤곽과형태그리고침범위치를알수있었다. 국소적뇌피질이형성증에서는두꺼워진뇌이랑과피질면이평활하며커진경우와피질면이톱니모양으로커진뇌이랑의부분이잘표현되었고, 침범된뇌이랑과뇌고랑부위가주위의정상부위와정확하게경계지워졌다 (Fig. 1). 2명의무뇌회증에서한명은양측전두-두정엽에병변이있었고다른한명은양측두정-후두-측두엽에병변이있었으며전두-두정엽에병변이있는증례에서는전두엽과두정엽이하나의덩어리로보이면서중심구 (central sulcus) 부위만뇌고랑의모양을일부보이고있었고뇌이랑의면은부드럽지않고울퉁불퉁하였다. 또한, 정상부위와병변부위가정확하게구분되어보였다 (Fig. 2). 4명의분열뇌증에서는전두엽과두정엽부위에분열된뇌의틈 (cleft) 이있었고전두엽과두정엽의뇌이랑부분이틈주위를둘러싼바퀴모양으로구성되어있었으며, 뇌고랑부위는정상보다깊고뚜렷하게보였고정상뇌이랑의크기보다크고작은뇌이랑의모양을확인하였으며뇌이랑의크기가증가한부분은 2차원영상에서뇌피질이형성증이동반되어있었다. 또한, 열린분열뇌증에서는병변중심틈이넓었지만닫힌분열뇌증에서는좁았다 (Fig. 3). 2명의일측성거대뇌증에서는병변측두정엽과후두엽부위가반대편보다용량이커져있었으며정상보다 2~3배크고면이고르지않은뇌이랑이병변측전두엽의뒷부분부터두정엽, 그리고후두엽에놓여있었다 (Fig. 4). 2명의선천성양측실비안주위증후군에서는양측실비안열 (sylvian fissure) 이열려있고도 (insular cortex) 피질이노출되어있었으며노출된도피질도두껍고면이울퉁불퉁해있었고전두엽, 측두엽을포함된대부분의뇌이랑이수직방향으로배치되어있었다 (Fig. 5). 이중피질증후군에서는 3차원표면연출영상에서뇌이랑과뇌고랑에이상소견을보이지않았다 (Fig. 6). 고찰뇌피질은위치에따른기능적구조로되어있으므로비침습적으로실제뇌의표면해부학적구조를보는것은신경질환의진단에매우도움이된다. 보편적인자기공명영상에서각촬영면에따라뇌이랑과뇌고랑이잘라지기때문에연속된뇌의모양을정확하게인지하는것은어렵다. 뇌피질의뇌이랑과뇌고랑의형태학적이상을가진뇌피질

45 황승배외 Fig. 1. Focal cortical dysplasia. Axial and coronal MP RAGE T1 weighted images show the cortical dysplasia in right frontoparietal area(a). 3D surface rendering images show an enlarged right frontoparietal gyri. The involved gyri show irregular serrated surface in right superior and inferior frontal, parietal lobes. The abnormal gyral patterns of involved gyri are clearly delineated from surrounding normal gyri in right cerebral hemisphere arrows (b). a b 이형성증환자는지능이떨어지고언어발달장애등여러가지정신과육체적장애를보인다. 영상기술의발달특히자기공명영상의발달로 2차원적인병변의위치와뇌백질과뇌회질의이상소견은 T1강조영상, T2강조영상, 액체감쇄영상 (FLAIR) 등의신호강도의변화를확인하여진단이가능해졌다. 하지만, 뇌표면의뇌이랑과뇌고랑의 3차원적인모양과위치관계는표현이어려웠다. 이를해결하기위하여경사자장을이용한 3차원 T1 강조영상인 MP-RAGE 기법으로나온 MR 데이터를 VoxelPlus 로옮겨 3차원뇌표면연출영상을만들어실제뇌표면의뇌이랑과뇌고랑의모양과윤곽및위치를파악하고병변과정상부위의경계와병변이침범된뇌고랑의크기와모양의정확한변화를확인할수있었다. 3차원표면연출영상은해부학적영역사이의신호강도차이에 의존하여개발된기법이다. 3차원 T1강조영상인 MP-RAGE 기법으로생성된데이터를이용하여뇌피질과지주막하공간사이의신호강도차이를이용하여서로다른조직간의화소신호강도차이에따라조직의분획화를시행하여뇌피질표면을 3차원영상으로표현한다 (12-15). 3차원표면연출영상을좋은영상으로만들기위해서는 3D MP-RAGE T1강조영상의대조도와공간적인화상의질이좋아야한다. 대조도가좋지못하면 3차원표면연출영상을소프트웨어자체만으로는자동적으로만들지못하며뇌표면이표현되지않은부위는인위적으로조정하여영상을만들어야하고시간도많이소요된다. 3차원표면연출영상의단점은국소적뇌피질이형성증에서보이는뇌회질과뇌백질사이경계면의변화를알수없고정상 4~5 mm보다도두꺼운뇌회질의내부적인두께를볼수없으

46 뇌피질이형성증의 3 차원뇌표면연출영상 며 T1강조영상, T2강조영상, FLAIR 등여러가지영상조건에따른신호강도의차이를보이는뇌회질과뇌백질의변화를알수가없다. 또한, 3차원표면연출영상에서는임의적으로선택된색채를사용하여영상을구성하기때문에뇌회질의신호변화를알수가없다. 본연구에서사용된 Voxel Plus 뿐만아니라 Rapidia, Voxar, Vitrea 등여러가지 3차원영상을만들수있는소프트웨어를따로구입해야하는경제적부담이있으며이전에비해서짧아졌지만 15분정도의영상구성시간이필 요하고또한숙련된인원이필요하다. 이전에는 3차원표면연출영상을사용된소프트웨어에서만볼수있고필름작업으로가능하지않았지만, 최근에는 PACS(picture archiving and communication system) 에저장하여 3차원영상으로볼수있게되었다. 뇌피질이형성증환자는대부분간질이발생하며수술적치료를받는경우에간질병소를얼마나완전하게절제하는것이매우중요하다. 대부분의뇌피질이형성증은전두엽과두정엽에 Fig. 2. Lissencephaly. 3D surface rendering images show scant sulcation with a thick and smooth gyral pattern in both frontoparietal cortex. Fig. 3. Schizencephaly. 3D surface rendering images show open-lip schizencephalic defect in right-side and closed-lip defect in left-side lined by pachygyria. There are central cleft with radiating thickened gyri of right frontoparietal lobes

47 황승배외 서주로발생하기때문에이부위의간질병소절제시에는운동, 감각과언어중추를정확히확인하여보존하면서간질병소를충분히제거하여야한다 (4-6). 뇌피질이형성증환자는대뇌에부분적으로뇌신경세포와신경섬유의비정상적인배열로특징되어지는데자기공명영상에서는뇌백질의비정상신호강도, 뇌회질-백질사이의신호강도차이의감소로경계가불분명해지고결절과밴드모양의뇌수질의두께가증가하며이러한소견은 2D MR 영상에서확인이가능하다. 그러나수술전 2D MR 영상은병변부위와주위정상적인뇌이랑과뇌고랑부위와 의정확한연관성뿐만아니라배열을정확히확인하는데어려움이있다. 병변부위와중요기능을가진뇌피질부위와의국소적인해부학적관계는단지수술시야에서직접확인하여치료되었으나뇌피질에대한 3차원표면연출영상이가능하여, 수술전에병변과운동, 감각과언어중추영역과의연관성을 3차원적인시각으로확인할수있어수술전치료계획에큰도움이될수있다 (10, 11, 13-16). 본원에서는간질의수술적치료전모든환자에서 3차원표면연출영상을만들어정확한병변의침범위치와모양을 3차원적으로제공함으로써수술전계획에매 Fig. 4. Hemimegalencephaly. 3D surface rendering images show an enlarged right cerebral hemisphere with thickened gyri in right superior frontal, parietal and occipital lobes. Fig. 5. Congenital bilateral perisylvian syndrome. The characteristic 3D surface rendering images show opened both sylvian fissure. The exposed insular cortex consists of the irregular thickened gyral pattern. Both temporal lobes consists of vertically oriented gyri

48 뇌피질이형성증의 3 차원뇌표면연출영상 Fig. 6. Double cortex syndrome. Areas which are clearly shown are: precentral gyrus, postcentral gyrus, superior parietal lobules, precentral sulcus, central sulcus. There are normal findings of brain sulcal and gyral pattern. 우유용하게이용되고있으며저자들의연구에서도 3차원표면연출영상에서병변부위의비정상적인뇌이랑의형태, 위축된뇌이랑와확장된뇌고랑의형태를찾을수있었으며, 병변주위의정상적인뇌이랑와뇌고랑과의정확한연관성을확인하여수술시간질병소의충분하고정확한절제에큰도움이되었다. 매끄러운뇌표면을가진무뇌회증은경련, 근력저하, 작은뇌 (microcephaly) 와얼굴기형을보이는질환으로완전한뇌이랑없음증 (agyria) 과일부큰뇌이랑증 (pachygyria) 을포함한불완전한모양의뇌이랑없음증이있고피질은두껍고피질하백질은얇으며정상적인뇌회질-백질의깍지낌 (interdigitation) 이부족하다. 불완전한덮개화 (opercularization) 에의해서실비안열은얇고뇌의모양은타원형또한모래시계 (hourglass) 모양을보인다 (17-19). 3차원표면연출영상에서는전두-두정엽에병변이있는증례에서전두엽과두정엽이하나의덩어리로보이면서중심구 (central sulcus) 부위만뇌고랑의모양을일부보이고있었고덩어리모양으로보인뇌이랑의면은부드럽지않고울퉁불퉁하였다 (Fig. 1). 분열뇌증은자기공명영상으로쉽게진단되며대뇌의갈라진틈 (cleft) 을볼수있고그틈을둘러싸고있는비정상적으로두꺼워진뇌피질을확인할수있으며, 주위에뇌피질이형성증을동반하는경우가많다 (20-22). 3차원표면연출영상에서는전두엽, 두정엽, 측두엽에상관없이엽을넘어서벌어진틈을둘러싸기위해틈을중심으로방사성원형모양으로뇌이랑과뇌고랑이배열되어있어병변을중심으로뇌이랑과뇌고랑이좌우뇌에서전체적으로재배치되어있었으며동반된뇌피질이형성증에의해일부뇌이랑은두꺼워져있었다 (Fig. 2). 일측성거대뇌증은대뇌의반구가커지면서이형성과오종으로확대되는질환으로이소증 (heterotopias) 이나별아교세포양 (astrocytosis) 과같은뇌백질의다양한정도의비정상적인 T1과 T2의길어짐으로인해뇌회질-백질의경계부위가불분명해지고병변측의측뇌실이커지는질환이다 (23, 24). 3차원표면연출영상에서는병변부위의두정엽과후두엽부위가반대편보다용량이커져있으며정상보다 2~3배크고면이고르지않은뇌이랑이병변쪽전두엽의뒷부분부터두정엽, 그리고후두엽에놓여있었다 (Fig. 3). 선천성양측실비안주위증후군은양측실비안주위뇌피질이두껍고덮개가이형성되어실비안열이열려있으며거짓연수마비 (pseudobulbar palsy), 간질, 인지기능장애를보인다 (25-27). 3차원표면연출영상에서는양측실비안열을덮고있던덮개에결손이있어도 (insular cortex) 피질이노출되어있으며노출된도피질도두껍고면이울퉁불퉁해있고전두엽, 측두엽을포함된대부분의뇌이랑이수직방향으로배치되어있었다 (Fig. 4). 국소적뇌피질이형성증은대뇌피질일부에비정상적인신경세포와아교 (glial) 세포가있는질환으로뇌회질과백질사이의경계가불분명해지며부분적으로뇌피질이두꺼워진다. 커다란뇌이랑과넓거나깊은골을가지고있다. 3차원표면연출영상에서는두꺼워진뇌이랑과피질면이평활하며커진경우와피질면이톱니모양으로커진뇌이랑의부분이잘표현되었고침범된범위와주위의정상뇌이랑과뇌고랑이정확하게경계지워졌다 (Fig. 5). 이중피질증후군은여자에서주로일어나는 X연관우성유전 (X-linked dominant inheritance) 으로자기공명영상에서얇은뇌백질에의해뇌회질이뇌피질과뇌피질하뇌회질로나뉘어진다 (28). 뇌피질은정상이거나큰뇌이랑증 (pachygyria) 패턴을보인다. 본증례에서는 3차원표면연출영상에서병변이뇌표면에침범되지않고뇌백질에또다른뇌회질이있는모양으로표현되기때문에비정상적인뇌이랑과뇌고랑의윤곽과형태를

49 황승배외 보이지않았다 (Fig. 6). 결론적으로 3차원뇌표면연출영상은뇌피질이형성증환자에서 3차원적인뇌이랑과뇌고랑의정확한모양과침범범위그리고주위정상구조물과의관계, 해부학적인이상소견을영상의학적으로정확하게표현하였고간질병소의정확한해부학적위치및주위의중요한운동, 감각과언어중추부위와의관계를파악할수있었다. 따라서뇌피질이형성증환자에서 3차원뇌표면연출영상은정확한병변의침범위치와모양을 3차원적으로제공함으로써수술전계획에매우유용하게이용할수있다. 참고문헌 1.Kerä nen T, Riekkinen P. Severe epilepsy: diagnostic and epidemiological aspects. Acta Neurol Scand Suppl 1988;117: Palmini A, Andermann F, Olivier A, Tampieri D, Robitaille Y, Andermann E, et al. Focal neuronal migration disorders and intractable partial epilepsy: a study of 30 patients. Ann Neurol 1991;30: Vital A, Marchal C, Loiseau H, Rougier A, Pedespan JM, Rivel J, et al. Glial and neuronoglial malformative lesions associated with medically intractable epilepsy. Acta Neuropathol 1994;87: Pedespan JM, Loiseas H, Vital A, Marchal C, Fontan D, Rougier A. Surgical treatment of an early epileptic encephalopathy with suppression bursts and focal cortical dysplasia. Epilepsia 1995;36: Palmini A, Andermann F, Olivier A, Tampieri D, Robitaille Y. Focal neuronal migration disorders and intractable partial epilepsy: results of surgical treatment. Ann Neurol 1991;30: Devaux B, Chassoux F, Landre E, Turak B, Abou-Salma Z, Mann M, et al. Surgical resections in functional areas: report of 89 cases. Neurochirurgie 2008;54: Spencer SS, Berg AT, Victrey BG, Sperling MR, Bazil CW, Shinnar S, et al. Initial outcomes in the multicenter study of epilepsy surgery. Neurology 2003;61: Lee BC, Schmidt RE, Hatfield GA, Bourgeois B, Park TS. MRI of focal cortical dysplasia. Neuroradiology 1998;40: Kuzniecky R, Garcia JH, Faught E, Morawetz RB. Cortical dysplasia in temporal lobe epilepsy: magnetic resonance imaging correlations. Ann Neurol 1991;29: Hattingen E, Good C, Weidauer S, Herminghaus S, Raab P, Marquardt G, et al. Brain surface reformatted images for fast and easy localization of perirolandic lesions. J Neurosurg 2005;102: Araujo D, Machado HR, Oliveira RS, Terra-Bustamante V, Barros de Araujo D, Santos AC, et al. Brain surface reformatted imaging (BSRI) in surgical planning for resections around eloquent cortex. Childs Nerv Syst 2006;22: Mugler III JP, Brookeman JR. Rapid three-dimensional T1- weighted MR imaging with the MP-RAGE sequence. J Magn Reson Imaging 1991;1: Kulynych JJ, Vladar K, Jones DW, Weinberger DR. Three-dimensional surface rendering in MRI morphometry: a study of the planum temporale. J Comput Assist Tomogr 1993;17: Levin DN, Hu XP, Tan KK, Galhotra S. Surface of the brain: three-dimensional MR images created with volume rendering. Radiology 1989;171: Gong X, Fang M, Wang J, Sun J, Zhang X, Kwong WH, et al. Three-dimensional reconstruction of brain surface anatomy based on magnetic resonance imaging diffusion weighted imaging: a new approach. J Biomed Sci 2004;11: Lee BCP, Hatfield G, Park TS, Kaufman BA. MR imaging surface display of the cerebral cortex in children. Pediatr Radiol 1997;27: Abdel Razek AAK, Kandell AY, Elsorogy LG, Elmongy A, Basett AA. Disorders of cortical formation: MR imaging features. AJNR Am J Neuroradiol 2009;30: Byrd SE, Osborn RE, Bohan TP, Naidich TP. The CT and MR evaluation of migrational disorders of the brain. Part I. lissencephaly and pachygyria. Pediatr Radiol 1989;19: de Rijk-van Andel JF, van der Knaap MR, Valk J, Arts WF. Neuroimaging in lissencephaly type I. Neuroradiology 1991;33: Barkovich AJ, Kjos BO. Schizencephaly: correlation of clinical findings with MR characteristics. AJNR Am J Neuroradiol 1992;13: Lopes CF, Cendes F, Piovesana AM, Torres F, Lopes-Cendes I, Montenegro MA, et al. Epileptic features of patients with unilateral and bilateral schizencephaly. J Child Neurol 2006;21: Packard AM, Miller VS, Delgado MR. Schizencephaly: correlations of clinical and radiologic features. Neurology 1997;48: Nakahashi M, Sato N, Yagishita A, Ota M, Saito Y, Surgai K, et al. Clinical and imaging characteristics of localized megalencephaly: a retrospective comparison of diffuse hemimegalencephaly and multilobar cortical dysplasia. Neuroradiology 2009;51: Flores-Sarnat L. Hemimegalencephaly: part 1. Genetic, clinical, and imaging aspects. J Child Neurol 2002;17: Donders J, Mullarkey SK, Allchin J. Congenital bilateral perisylvian syndrome: a case study. Clin Neuropsychol 2009;23: Margari L, Presicci A, Ventura P, Buttiglione M, Andreula C, Perniola T. Congenital bilateral perisylvian syndrome with partial epilepsy. Case report with long term follow up. Brain Dev 2005;27: Luat AF, Bernardi B, Chygani HT. Congenital perisylvian syndrome: MRI and glucose PET correlations. Pediatr Neurol 2006;35: Koutsouraki E, Timplalexi G, Papadopoulou Z, Costa V, Baloyannis S. A case of intractable epilepsy in a double cortex syndrome. Int J Neurosci 2008;118:

50 뇌피질이형성증의 3 차원뇌표면연출영상 J. Korean Soc. Magn. Reson. Med. 14: (2010) Three-Dimensional Brain Surface Rendering Imaging of Cortical Dysplasia Seung Bae Hwang, Hyo Sung Kwak, Sang Yong Lee, Gong Yong Jin, Young Min Han, Gyung Ho Chung Department of Radiology, Chonbuk National University Medical School Jeonju, Jeonbuk, Korea Purpose : The study was to evaluate the localization of the abnormal gyral and sulcal patterns obtained by means of brain surface rendering imaging. Materials and Methods : Nineteen patients with cortical dysplasia who underwent brain surface rendering MR imaging were included in this study. We acquired MP-RAGE sequence and created the 3-D surface rendering MR images by using VoxelPlus. Anatomical locations and configurations of abnormal gyri and sulci were reviewed. Results : Abnormal gyral and sulcal patterns were seen 18 in 19 patients. The configuration and orientation of affected gyri and sulci were clearly evaluated in the brain surface rendering images. In a lissencephaly, the a cortex was not delineated and showed markedly thick and smooth gyral pattern. In a schizencephaly, there were wheel shaped broad gyral pattern around the cleft. In a hemimegalencephaly, an affected hemisphere were enlarged and displayed thick and wide gyral pattern. In CBPS, the insular cortex was exposed and the gyri of the lesion were thickened. In focal cortical dysplasia, there were irregular serrated or thick and enlarged gyri. Conclusion : Brain surface rendering MR imaging is useful for the evaluation of a detailed gyral pattern and accurate involvement site of abnormal gyri. Index words : Brain Magnetic resonance (MR) Cortical dysplasia Surface rendering Address reprint requests to : Gyung Ho Chung, M.D., Department of Radiology, Chonbuk National University Medical School, , Keumam-dong, Deokjin-gu, Jeonju, Jeonbuk , Korea. Tel Fax chunggh@chonbuk.ac.kr

51 MR Imaging Findings of Parosteal Lipoma: Case Report Hyoung-ju Bae 1, Suk-Joo Hong 1, Yelim Kim 1, Eun-Young Kang 1, Hak Jun Kim 2, Young Jun Ryu 3, Woon Yong Jung 3 Parosteal lipoma is a rare benign tumor containing mature adipose tissue having an intimate relationship to the periosteum. Characteristically, this tumor presents as a lipomatous mass adjacent to bone, eliciting variable reactive changes in the underlying cortex. We report a case of parosteal lipoma of the foot. The MR findings consisted of juxtacortical lipomatous mass abutting to bony protuberance, with internal fibrous striations, and osseous reaction in the adjacent bone. By the aid of multiplanar imaging capability, high spatial and contrast resolution of MRI, characteristic features of parosteal lipoma can lead to diagnosis on imaging. Index words : Fatty neoplasm Lipoma Magnetic resonance imaging (MRI) Introduction Parosteal lipoma is a rare benign fatty neoplasm containing mature adipose tissue that is firmly adherent to the periosteum of the underlying bone (1-5). The incidence of this tumor is 0.3% of all lipomas (2, 3, 6-11). Parosteal lipoma occurs almost exclusively in the extremities and is always solitary (3, 8-11). This tumor occurs most commonly in the 5 th -7 th decades and presents as a painless, non-tender slowly growing mass which is present for an average of 8-10 years (3, 8-11). To the best of our knowledge, there has been only one case report of the magnetic resonance (MR) imaging features of parosteal lipoma from Korea (12). We report a case of parosteal lipoma of the foot focusing on MR imaging findings. Case Report A 48-year-old woman presented with a progressive painful, palpable mass at the lateral aspect of her right foot, plantar surface. The patient didn t complain any symptoms related to nerve compression. Lateral JKSMRM 14: (2010) 1 Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea 2 Department of Orthopedic Surgery, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea 3 Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea Received; September 2, 2010, revised; September 29, 2010, accepted; October 19, 2010 Corresponding author : Suk-Joo Hong, M.D., Department of Radiology, Korea University Guro Hospital, Korea University College of Medicine, 97 Guro-dong, Guro-gu, Seoul , Korea. Tel Fax hongsj@korea.ac.kr

52 MR Imaging Findings of Parosteal Lipoma radiograph of the right foot showed an irregular bony protruding lesion from the right 5 th metatarsal base toward the plantar surface, with a surrounding wellcircumscribed low-density soft tissue mass-like lesion (Fig. 1a). On non-enhanced coronal T1-weighted and axial T2-weighted MR images, a multi-lobulated and well-marginated high signal intensity mass with several thin low signal striations was noted in the plantar surface of right mid foot, between the 1 st and 2 nd muscle layers, just deep to the flexor digitorum brevis muscle a c b d e Fig. 1. A 48-year-old female patient with parosteal lipoma in the right foot. (a) Lateral radiograph of the right foot shows an irregular bony protrusion from right 5 th metatarsal base with surrounding low-density soft tissue mass-like lesion (arrows). Non-enhanced coronal T1-weighted (b), axial T2-weighted (c) MR images show a multi-lobulated well-marginated high signal intensity mass (asterisks) with several thin low signal striations(open arrows) in the plantar surface of right mid foot just deep to the flexor digitorum brevis muscle. (d) Fat-suppressed coronal T2-weighted image shows low signal intensity conversion in almost whole area of the mass (asterisks) and high signal thin striations (open arrow). (e) Post-contrast fat-saturated coronal T1-weighted image shows minimal enhancement in the internal striations (open arrow) without demonstrable enhancing solid portion in the mass. A focal nodular enhancement is seen in the junction between the bony protuberance and the mass (arrowheads). A peripheral ill-defined subtle enhancement is seen in the mass which corresponds to the high signal portion on pre-contrast fat-suppressed T2-weighted image (thick arrows in Fig. b, d, e), representing secondary focal cystic change. The mass shows irregular attachment (arrowheads in Fig. b, d, e) to the cortical based bony excrescence arising from the inferior aspect of the 5 th metatarsal base (B on Fig. b-e). Medullary continuation between bony protuberance and the 5 th metatarsal bone is not definite on the precontrast T1-weighted coronal image, although suspected in the other pulse sequences (thin arrows in Fig. b, d, e). Focal cortical erosion is combined in the inferomedial side of the 5 th metatarsal base (curved arrows in Fig. b-e)

53 Hyoung-ju Bae et al Fig. 1. (f) Photomicrograph ( 40, H-E stain) reveals the junction between bony protuberance (B) and the lipoma (L) with reactive cortical hypertrophic changes, cortical erosions (arrow), and fibrovascular proliferation of the intervening periosteum (P). f (Fig. 1b, c). On fat-suppressed coronal T2-weighted images, almost whole area of the mass showed low signal intensity conversion representing fatty signal intensity with high signal thin striations (Fig. 1d). On enhanced fat-saturated coronal T1-weighted MR images, nearly most of the entire mass showed low signal intensity and minimal central thin septal enhancement was seen without a demonstrable enhancing solid portion, representing a benign lipomatous lesion (Fig. 1e). A focal nodular enhancement was seen in the junction between the mass and the bony protuberance, raising the possibility of reactive soft tissue change (arrowheads in Fig. 1b, d, e). A peripheral ill-defined subtle enhancement is seen in the soft tissue mass which corresponded to the high signal intensity portion on precontrast fat-suppressed T2-weighted images (thick arrows in Fig. 1b, d, e), representing secondary focal cystic change of the large lipomatous lesion. The mass showed irregular attachment to the cortical based bony excrescence arising from the inferior cortex of 5 th metatarsal base (Fig. 1b-e). There was no definite medullary continuation between the bony protuberance and the 5 th metatarsal bone on pre-contrast T1-weighted coronal images (Thin arrow in Fig. 1b). Although medullary continuation was suspected on the coronal fatsuppressed T2-weighted and post-contrast T1-weighted images, they are considered less reliable in the evaluation of the osseous medulla than T1-weighted images (thin arrows in Fig. 1b, d, e). The flexor digitorum brevis muscle was compressed, thinned, and was bulging inferiorly toward the plantar surface, without internal fatty striation suggesting atrophic change of the muscle (Fig. 1b, d, e). Focal external pressure erosion was combined in the inferior cortex of the 5 th metatarsal base, medial to the bony excrescence, by a small lobulated portion of the soft tissue mass (curved arrows in Fig. 1b-e). The patient underwent complete mass excision including excision of the bony protuberance. At surgery, the lipomatous mass was yellowish, soft, and encapsulated, and strongly adherent to the underlying periosteum of the 5th metatarsal base and the bony protuberance, requiring subperiosteal dissection and the use of an osteotome for the removal of the soft tissue mass and the bony protuberance. The histologic diagnosis of the soft tissue mass was lipoma composed of mature adult fat (Fig. 1f). The junction between bony protuberance and the lipoma showed reactive cortical hypertrophic changes, cortical erosions, and fibrovascular proliferation of the intervening periosteum (Fig. 1f). There was no detectable cartilage or osteoid metaplasia adjacent to the osseous excrescence. Discussion Lipoma is the most common benign tumor of the soft tissues and can be classified according to their location of origin, such as subcutaneous, intramuscular, intermuscular, intraosseous, intracortical, and parosteal. Parosteal lipoma is a rare benign fatty neoplasm containing mature adipose tissue that arises directly

54 MR Imaging Findings of Parosteal Lipoma adjacent to bone, in continuity with the underlying periosteum (1-5). The incidence of this tumor is 0.3% of all lipomas (2, 3, 6-11). The most common sites of origin for parosteal lipomas are the thigh adjacent to the femur or the upper extremity near the proximal radius (3, 8-11). Other sites include the tibia, humerus, scapula, clavicle, ribs, pelvis, metacarpals, metatarsals, mandible, and skull. Patients with parosteal lipoma range from the 5 th -7 th decades and usually present with a history of a slowly growing, large, painless and nontender immobile mass not fixed to the skin (3, 8-11). Occasionally, compressive neuropathy may occur if the mass is sufficiently large or located in a strategic location that allows encroachment upon the nerve such as in the proximal radius (6, 7, 9). Pathologically, parosteal lipomas are adherent to the underlying periosteum and are circumscribed greasy yellowish masses with thin, fibrous capsule. These lesions are composed of mature adult fat identical to soft-tissue lipomas. Cartilage, osteoid metaplasia, and areas of osseous excrescences or cortical thickening extending from and attaching the lesion to the bone surface are common (4, 13). These osseous excrescences do not show cortical or medullary continuity with the adjacent bone (2, 3). This relationship to the underlying bone distinguishes this lesion from a soft-tissue lipoma. The radiographic features of parosteal lipoma are usually characteristic. In a study of parosteal lipoma by Fleming et al, nearly 70% of patients had abnormal underlying bone and 50% had osseous reaction. The most frequent osseous reactive changes included bowing of bone or cortical erosion secondary to the adjacent lipomatous mass. In a study by Murphey et al (2), the major radiographic features of parosteal lipoma included a juxtacortical radiolucent lipomatous mass with varying degrees of septation associated with surface bone productive changes ranging from very subtle to obvious cortical thickening and variably sized ossific protuberances or excrescences. These areas of cortical abnormality do not show medullary continuity with the underlying bone, as would be expected in an osteochondroma (2, 3). On MR images, the tumor is identified as a juxtacortical mass with signal intensity identical to that of subcutaneous fat, regardless of pulse sequence (2). Heterogeneity in these lesions is invariably present and corresponds to the pathologic components in the lesion. Areas with intermediate signal intensity on T1- weighted images that are high signal intensity on T2- weighted images represent the cartilaginous components in parosteal lipoma (2). Fibrovascular septa may cause a lobulated appearance of the fat component, with low-signal-intensity strands on T1- weighted images that become higher in signal intensity on the long TR images (particularly with fat suppression). These thin fibrous septa are different from those of well-differentiated liposarcoma, which are thick and show marked enhancement (14). Larger areas of bone production surrounded by the lipomatous components are also well demonstrated with MR imaging. Adjacent muscle atrophy, poorly demonstrated by CT, is identified on MR images as increased striations of fat in the affected muscle and is caused by associated nerve entrapment(2). This finding is best appreciated on T2-weighted images because of the decreased signal intensity of normal muscle relative to fat. In contrast with radiography and CT imaging, which highlights the bony protuberance and changes of underlying bone, MR imaging best demonstrates the soft tissue portion and relationship of the tumor to the underlying native bone and muscle, and this information is important for surgical planning because parosteal lipoma is usually firmly adherent to the underlying cortex at the site of surface bone production. In our case, bony protuberance and surrounding juxtacortical benign lipoma was seen in the plantar surface of the right 5 th metatarsal base, with focal cortical erosion, suggestive of the typical findings of parosteal lipoma, which were well appreciated in MR imaging. The exclusion of medullary continuity between bony protuberance and the adjacent bone, which is the differential diagnostic clue from osteochondroma, was also well appreciated in the precontrast T1-weighted images. Additionally, no findings related with nerve compression were detected in MR imaging, providing confidence to the clinical examination results. In summary, by the aid of multiplanar imaging capability, high spatial and contrast resolution of MRI, characteristic features of parosteal lipoma can lead to a reliable diagnosis on imaging. Recognition of these characteristic features is important because of the apparent lack of malignant potential of parosteal

55 Hyoung-ju Bae et al lipoma. References 1.Kransdorf MJ, Moser RP Jr., Meis JM, Meyer CA. Fatcontaining soft-tissue masses of the extremities. Radiographics 1991;11: Murphey MD, Johnson DL, Bhatia PS, Neff JR, Rosenthal HG, Walker CW. Parosteal lipoma: MR imaging characteristics. AJR Am J Roentgenol 1994;162: Ramos A, Castello J, Sartoris DJ, Greenway GD, Resnick D, Haghighi P. Osseous lipoma: CT appearance. Radiology 1985;157: Jones JG, Habermann ET, Dorfman HD. Case report 553. Parosteal ossifying lipoma of femur. Skeletal Radiol 1989;18: Kawashima A, Magid D, Fishman EK, Hruban RH, Ney DR. Parosteal ossifying lipoma: CT and MR findings. J Comput Assist Tomogr 1993;17: Nishida J, Shimamura T, Ehara S, Shiraishi H, Sato T, Abe M. Posterior interosseous nerve palsy caused by parosteal lipoma of proximal radius. Skeletal Radiol 1998;27: Henrique A. A high radial neuropathy by parosteal lipoma compression. J Shoulder Elbow Surg 2002;11: Jacobs P. Parosteal lipoma with hyperostosis. Clin Radiol 1972;23: Moon N, Marmor L. Parostel Lipoma of the Proximal Part of the Radius. A Clinical Entity with Frequent Radial-Nerve Injury. J Bone Joint Surg Am 1964;46: Krajewska I, Vernon-Roberts B, Sorby-Adams G. Parosteal (periosteal) lipoma. Pathology 1988;20: Berry JB, Moiel RH. Parosteal lipoma producing paralysis of the deep radial nerve. South Med J 1973;66: Yu JS, Weis L, Becker W. MR imaging of a parosteal lipoma. Clin Imaging 2000;24: Demos TC, Bruno E, Armin A, Dobozi WR. Parosteal lipoma with enlarging osteochondroma. AJR Am J Roentgenol 1984;143: Ohguri T, Aoki T, Hisaoka M, Watanabe H, Nakamura K, Hashimoto H, et al. Differential diagnosis of benign peripheral lipoma from well-differentiated liposarcoma on MR imaging: is comparison of margins and internal characteristics useful? AJR Am J Roentgenol 2003;180: 대한자기공명의과학회지 14: (2010) 뼈주위지방종의자기공명영상소견 : 증례보고 1 고려대학교구로병원영상의학과 2 고려대학교구로병원정형외과 3 고려대학교구로병원병리과 배형주 1 홍석주 1 김예림 1 강은영 1 김학준 2 류영준 3 정원용 2 뼈주위지방종은골막과밀접한관련성을지니며발생하는드문양성지방종으로조직소견은전형적인연부조직지방종과같은성숙지방세포로구성된다. 영상에서특징적으로뼈와인접한지방성의덩어리로나타나며인접한골피질에다양한반응성변화를일으킨다. 자기공명영상에서는뼈주위에위치한양성지방종, 이와연결된뼈의돌기또는반응성골피질변화, 또한신경압박에의한이차적근육퇴행등의소견을관찰할수있다. 이보고에서는중족골에연해발생한뼈주위지방종의증례를자기공명영상소견을중심으로기술하고자한다. 통신저자 : 홍석주, ( ) 서울특별시구로구구로동 97, 고려대학교구로병원영상의학과 Tel Fax hongsj@korea.ac.kr

56 MR Images and 1 H MR Spectroscopy of Enteric Duplication Cyst of the Pancreas in an Adult Sung Hee Park 1, Mi Young Kim 1, Chang Hae Suh 1, Keon Young Lee 2, Suk Jin Choi 3, Jae Young Cho 4 Enteric duplications associated with the pancreas are especially uncommon, and the differential diagnosis of pancreatic duplication cysts is often difficult, and may be confused with various cystic lesions of the pancreas. We report a case of pancreatic duplication cyst; present the images and laboratory findings including cyst fluid tumor markers. MR and MRS findings enabled the detection of the location, contour, characteristics of cystic fluid and definition of tissue planes between the lesion and adjacent structures, providing useful information for an accurate surgical approach. Index words : Pancreas Duplication cyst Magnetic resonance (MR) Magnetic resonance spectroscopy (MRS) Computed tomography (CT) Introduction Enteric duplication is an ectopic cyst or a tubular structure composed of smooth muscles surrounding mucosa of the gastrointestinal tract (1). Most cases of duplication are present before the age of 2 years as an acute abdomen or bowel obstruction (2). Diagnosis of duplication cyst is uncommon in adults, and enteric duplication within the pancreas is especially uncommon and difficult to diagnose because it may be confused with pancreatic pseudocyst, mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, choledochal cyst or lymphangioma. We report clinical findings and imaging of pancreatic duplication cyst in an adult. To our knowledge, this is the first reported case of a pancreatic duplication cyst in an adult demonstrated by MR imaging and MR Spectroscopy. Case Report A 46-year-old woman with abdominal pain was JKSMRM 14: (2010) 1 Department of Radiology, Inha University School of Medicine, Inha University Hospital, Korea 2 Department of Surgery, Inha University School of Medicine, Inha University Hospital, Korea 3 Department of Pathology, Inha University School of Medicine, Inha University Hospital, Korea 4 Department of Biology, College of Arts and Science, New York University, 100 Washington Square E, New York, NY 10003, USA Received; September 6, 2010, revised; September 15, 2010, accepted; October 6, 2010 Corresponding author : Mi Young Kim, M.D., Department of Radiology, Inha University School of Medicine, Inha University Hospital, 7-206, 3-ga, Sinheung-dong, Jung-gu, Incheon , Korea. Tel Fax mykim@inha.ac.kr

57 Sung Hee Park et al referred to our hospital because of known pancreatic mass, diagnosed on ultrasonography 3 years ago. Her medical history was unremarkable. She previously had undergone tonsillectomy 5 years ago. On physical examination, the patient had a palpable abdominal mass on the right upper quadrant. Laboratory examinations revealed decreased serum hemoglobin (9.2 g/dl) and normal white cell count. The serum amylase, lipase, carbohydrate-associated antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were within normal limits. Ultrasonography and contrast enhanced computed tomography (CT) showed two homogeneous echogenic cystic masses, one 9 cm sized spherical shaped mass and the other one 11 3 cm sized tubular cystic mass each located in the pancreatic head and the body, respectively (Fig. 1a, b). MR imaging and MR spectroscopy (MRS) were performed (Sigma 1.5T GE. Milwaukee, WI, U.S.A.). T1-weighted (TR/TE, 100/4.2 msec) and T2-weighted (TR/TE, 1500/89 msec) MR images showed a well circumscribed cystic mass consisting of cm sized spherical and cm sized tubular cystic lesions in pancreatic head and body, respectively. The cystic lesions had homo- a b c d Fig. 1. (a) Ultrasound image shows a spherical (S) and tubular (T) cystic mass, containing relatively echogenic materials in spherical cyst of pancreatic head. (b) Contrast enhanced CT scan demonstrates a spherical and tubular cystic mass arising from the pancreatic head and partially invaded in body, and free distal portion of tubular cystic lesion (*). (c) Axial T1- weighted and (d) T2-weighted MR images reveal a hypointense and hyperintense cystic mass without septation or a mural nodule in the pancreatic head and body

58 MR Images and 1 H MR Spectroscopy of Enteric Duplication Cyst of the Pancreas in an Adult e f g h Fig. 1. (e) MRCP shows normal pancreatic main duct (arrowheads) without distension and a cystic mass (asterisk). (f) MR spectroscopy shows minimal peak in 1.31 ppm (*) and non-specific peaks. (g) Surgical specimen shows a dumbbell-shaped spherical (S, arrows) and tubular (T, arrowheads) mass partly covered by pancreatic tissue. It is filled with yellowish mucoid materials. Inner surface of the cyst is partly covered by necrotic debris. (h) Microscopic examination of the cystic mass shows mildly inflamed gastric antral and fundic mucosa along with intact submucosa, muscularis mucosa, and proper muscle coats (H&E 200). (i) The other portion of cystic mass comprised of respiratory mucosa and underlying normal smooth muscle coats (H&E 200). i

59 Sung Hee Park et al geneously hypointense fluid on T1-weighted images and hyperintense fluid within hypointense cystic wall on T2-weighted images (Fig. 1c, d). MRCP showed normal contour of the biliary duct and pancreatic duct without communication with the cystic lesions (Fig. 1e). In vivo MRS was performed with a free-breathing multivoxel point-resolved spectroscopy (PRESS) sequence (TR/TE=1500/30 msec, 2048-point acquisition, 2500 Hz bandwidth four averages). CHESS water suppression with 20 Hz bandwidth was obtained after semi-automated higher-order shimming. Outer volume suppression was achieved with six suppression bands placed three-dimensionaly around the lesions. Postprocessing was applied automatically with zero-order phase correction, zero-filling to 4096 points, and noise was removed with a low pass 800-ms Gaussian filter. The voxel of interest ( mm) was placed completely within the cyst. Spectroscopy revealed a short peak at 1.31 ppm, and there were no spectral peaks (Fig. 1f). Laparoscopic subtotal pancreatectomy was performed. During the surgery, a smooth-walled cyst was identified in the pancreatic head and partially embedded in the pancreatic body. The whole specimen containing cystic mass was removed, and free distal portion of tubular cystic lesion was not communicated with the pancreatic mid-body and tail. Aspiration of the cystic contents yielded thick yellowish fluid. The fluid was transferred for analysis of CA19-9, and CEA levels. Marked elevated levels of CA19-9 (> 2400 U/ml) and CEA (> 880 ng/ml) were reported. The resected specimen was a dumbbell-shaped cystic mass filled with yellowish mucoid material partly covered with the pancreatic tissue and the inner surface of the cyst was partly covered with necrotic debris (Fig. 1g). Pathological examination was consistent with an enteric duplication, and it demonstrated mildly inflamed gastric or respiratory mucosa (Fig. 1h, i). The post-operative course was uneventful, and she was discharged on postoperative day 29. Discussion Isolated duplication cyst is a rare congenital anomaly (1, 3), and occurs most commonly along the ileum, esophagus, or colon. Enteric duplication cyst contains smooth muscle layers and mucous membrane lining, occasionally gastric, intestinal, and respiratory epithelia. Enteric duplication typically lies on the paramesenteric border of the intestine, and generally do not communicate with the lumen, but may share smooth muscle layers with the adjacent bowel (1). However, it rarely occurs in such ectopic locations as the pancreas, biliary tree, and tongue. Although the embryology of duplication cyst remains unknown, enteric duplication cyst is thought to be the result of a diverticulum of the embryonic intestine that fails to undergo regression or defective recanalization of the alimentary tube during early fetal life (2). Both the stomach and pancreas arise as a bud from the primitive foregut. If the diverticulum forms on or near the pancreatic bud, a duplication cyst with pancreatic communication would result (4). The presenting symptoms are non-specific and can be revealed by complications such as infection, hematemesis, compression or carcinoma arising in the cyst (2). The symptoms of pancreatic duplication cyst are reported as recurrent abdominal pain caused either by recurrent pancreatitis or peptic ulceration (5). When radiologic images show pancreatic cystic mass, the differential diagnosis includes all cystic masses such as pancreatic pseudocyst, cystadenoma, intraductal papillary mucinous neoplasm, choledochal cyst, cystic lymphangioma, etc. Ultrasonography usually demonstrates an anechoic mass with good through transmission due to clear fluid contents or can also produce complex internal echoes with hemorrhage and infection. CT or MRI show the full extent of the duplication cyst, excluding noncystic masses, presence of hemorrhage or protein, and additional anomalies (6). This case of duplication cyst was partially located in the pancreatic head and did not adhere to the pancreatic body and tail. Coexistence of spherical and tubular countered cysts are a highly suggestive findings of duplication cyst. Although the fluid within the duplication cyst has homogenous high signal intensity on T2-weighted MR images, variable patterns of signal intensity are seen on T1-weighted MR images because of the presence of protein or hemorrhage. ERCP is a useful tool for biliary and pancreatic ductal anatomy and demonstrates any communication between the duplication cyst and the main pancreatic duct to aid in planning surgical approach. MR cholangiography is a noninvasive way to detect biliary abnormalities and relationship between the duplication cyst, common bile

60 MR Images and 1 H MR Spectroscopy of Enteric Duplication Cyst of the Pancreas in an Adult duct and pancreatic duct (5). On previous report, mediastinal foregut duplication cyst with in vivo 1 H MRS on a 1.5T magnet showing a large metabolite peak at 2.02 ppm, attributable to N- acetylated compounds in addition to smaller peak at 1.33 ppm, was considered to represent lipids (7). In our case, a short peak was detected at 1.31 ppm and no other peaks were demonstrated. The mucus secreted by respiratory epithelium and the mucous glands of the foregut cyst contain-glycoproteins that have N- acetylhexosamines as components and lipid breakdown products that are thought to contribute to the observed spectrum (7). The analysis of cystic fluid for the differential diagnosis of benign vs. premalignant or malignant pancreatic cystic lesions suggest that high CEA level predicts mucinous cystic neoplasm (2, 3, 8) and low levels of CEA or CA 19-9 suggest the presence of a serous cystadenoma or pseudocyst (8). In our case, the contents of the cyst revealed high levels of CEA and CA19-9, and there was no malignant lesion on pathologic examination. High concentrations of CEA and CA19-9 have been reported in a duplication cyst in the absence of malignancy (2). Although carcinoma arising from a duplication cyst is extremely rare, the production of oncofetal antigens by the epithelial lining of duplication cyst raises the problem of a precancerous condition in long standing intestinal duplications (2). Duplication cyst must be completely excised because it often has been the cause of morbidity. Adenocarcinoma has been reported in foregut duplications (9). Complete local resection of enteric duplication cysts in the pancreatic head can be performed for definitive management, avoiding the complications of more radical procedures. Local resection can prevent the development of pancreatic insufficiency in the young patients. The optimal treatment procedure for an enteric duplication cyst varies considerably, depending on its location in the pancreas (10). Identifying the presence or absence of communication with the pancreatic duct is very important for selecting appropriate surgical procedure. In conclusion, enteric duplication cyst of pancreas is a rare lesion in adult, and it should be included in the differential diagnosis of various cystic pancreatic lesions. We present a case of pancreatic duplication cyst, coexisting spherical and tubular cystic lesions partially located in the pancreatic head on radiologic images, that contains fluid with high CEA and CA 19-9 levels, and non-specific MR spectroscopy peaks. Radiologists should be aware of this rare case of pancreatic cystic lesion and imaging findings for differential diagnosis, which is significantly helpful in terms of accurate preoperative diagnosis and obtaining information for planning proper surgical approach for this condition. Acknowledgment This work was supported by INHA UNIVERSITY Research Grant. References 1.Siddiqui AM, Shamberger RC, Filler RM, Perez-Atayde AR, Lillehei CW. Enteric duplications of the pancreatic head: definitive management by local resection. J Pediatr Surg 1998;33: D Journo XB, Moutardier V, Turrini O, et al. Gastric duplication in an adult mimicking mucinous cystadenoma of the pancreas. J Clin Pathol 2004;57: Brugge WR, Lewandrowski K, Lee-Lewandrowski E, et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 2004;126: La Hei ER, Cohen RC. Antenatal detection of a pancreatic foregut duplication cyst. J Pediatr Surg 2001;36: Wong AM, Wong HF, Cheung YC, Wan YL, Ng KK, Kong MS. Duodenal duplication cyst: MRI features and the role of MR cholangiopancreatography in diagnosis. Pediatr Radiol 2002;32: Macpherson RI. Gastrointestinal tract duplications: clinical, pathologic, etiologic, and radiologic considerations. Radiographics 1993;13: Santhosh K, Thomas B, Varma L, et al. Metabolite signature of developmental foregut cyst on in vivo and in vitro (1)H MR spectroscopy. J Magn Reson Imaging 2008;28: van der Waaij LA, van Dullemen HM, Porte RJ. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointestinal Endoscopy 2005;62: Olsen JB, Clemmensen O, Andersen K. Adenocarcinoma arising in a foregut cyst of the mediastinum. Ann Thorac Surg 1991;51: Kohno M, Ikawa H, Konuma K, Masuyama H, Fukumoto H, Ogawa E, et al. Laparoscopic enucleation of a gastroenteric duplication cyst arising in a pancreatic tail that did not communicate with the pancreatic duct: report of a case. Surg Today 2010;40:

61 Sung Hee Park et al 대한자기공명의과학회지 14: (2010) 췌장중복낭의자기공명영상소견과수소자기공명분광법 : 증례보고 1 인하대학병원영상의학과 2 인하대학병원외과 3 인하대학병원병리과 4 뉴욕대학교자연과학대학생물학과 박성희 1 김미영 1 서창해 1 이건영 2 최석진 3 조재영 4 췌장의중복낭은성인에서매우드문병변으로췌장의다양한낭성병변들과감별진단이용이하지않다. 저자들은성인에서발견된췌장중복낭의영상소견들을알아보고임상소견및낭종액내종양표지자를포함한검사결과를함께보고하고자한다. 자기공명영상과 H-1 자기공명분광법소견들은췌장중복낭의위치, 형태, 낭종액의특성을진단하고주변구조물과의경계를구분하여보다정밀한수술적접근에유용한정보를제공한다. 통신저자 : 김미영, ( ) 인천광역시중구신흥동 3 가 7-206, 인하대학병원의과대학영상의학과 Tel Fax mykim@inha.ac.kr

62 Non-Functioning, Malignant Pancreatic Neuroendocrine Tumor in a 16-Year-old Boy: A Case Report Se Woong Lim 1, Young Hwan Lee 1, See Sung Choi 1, Hyun Sun Cho 2 We report the case of a 16-year-old boy with a solid pancreatic mass which proved to be a nonfunctioning, malignant pancreatic neuroendocrine tumor (PNET). In pediatric patients, malignant pancreatic tumors are rare, especially malignant PNET. When dynamic contrast enhanced MRI showed a well enhancing solid pancreatic tumor on arterial and delayed phases and combined with malignant features, such as vascular invasion, invasion of adjascent organs, and lymphadenopathy, we should include malignant pancreatic neuroendocrine tumor in the differential diagnosis of childhood pancreatic tumors. Index words : Pancreatic neuroendocrine tumor Islet cell tumor Children Magnetic resonance (MR) Although various types of pancreatic neoplasms have often been studied, malignant pancreatic endocrine tumors in children have rarely been reported in the medical literature. We herein present the CT and MR imaging findings, including MR cholangiopancreaticography (MRCP), of a nonfunctioning, malignant pancreatic neuroendocrine tumor (PNET) in a 16-yearold boy. To the best of our knowledge, this is the first such report in the radiology literature regarding the imaging findings of a malignant endocrine tumor of detected in a child. Case Report A 16-year-old boy suffered from epigastric pain, radiating to the right upper quadrant of the abdomen for one year. He visited a community clinic where ultrasound examination showed a mass-like lesion in the head of the pancreas. He was referred to our hospital for further study of the pancreas. On physical examination, a palpable abdominal mass was detected in the right upper quadrant of the abdomen. The laboratory studies including those regarding pancreatic enzymes and tumor markers, were within normal limits. JKSMRM 14: (2010) 1 Department of Radiology, Wonkwang University School of Medicine and Hospital 2 Department of Radiology, Inje University Sanggyepaik Hospital This paper was supported by Wonkwang university in Received; September 14, 2010, revised; September 29, 2010, accepted; October 19, 2010 Corresponding author : Young Hwan Lee, M.D., Department of Radiology, Wonkwang University Hospital, Shinyong-dong, Iksan, Jeonbuk , Korea. Tel Fax yjyh@wonkwang.ac.kr

63 Se Woong Lim et al Contrast-enhanced pancreas CT scan (Fig. 1a) yielded a 4 5 cm-size solid mass with a multilobulated contour and with inhomogeneous enhancement in the head of the pancreas. Multiple enlarged lymph nodes were noted on portocaval and aortocaval spaces, and along the root of the mesentery. The pancreatic parenchyma was atrophied with upstream dilatation of the main pancreatic duct. a b c d e Fig. 1. A 16-year-old boy with epigastric pain for one year. (a) Ccontrast-enhanced CT of the abdomen showed a multilobulated contoured solid mass with inhomogeneous enhancement in the region of the pancreatic head (arrows). (b) The axial T2-weighted MR image obtained at the same level as in A, depicts a multilobulated mass with heterogeneous high signal intensity. (c) The mass showed intermediate to low signal intensity on the axial T1-weighted MR image. (d) The mass revealed a reticular pattern of inhomogeneous enhancement on the late portal phase of dynamic gadolinium-enhanced T1-weighted MR image. (e) On the delayed phase of dynamic gadolinium-enhanced T1-weighted MR image, persistent and intense enhancement of the mass and multiple conglomerated metastatic lymphadenopathy were seen (arrow)

64 Non-Functioning, Malignant Pancreatic Neuroendocrine Tumor in a 16-Year-old Boy For further evaluation of the pancreatic mass, vascular invasion and bile duct obstruction, we performed pancreas MR imaging, including MR angiography and MRCP. The mass showed heterogeneous high signal intensity on T2-weighted image (Fig. 1b) and intermediate to low signal intensity on T1-weighted image (Fig. 1c). On dynamic T1- weighted MR image obtained after intravenous administration of gadolinium, the mass showed inhomogeneous enhancement with a reticular pattern on the portal phase (Fig. 1d) and persistent intense enhancement on the delayed phase (Fig. 1e). On f g h i Fig. 1. (f) MRCP showed that despite the large size of the mass, the common bile duct (arrow) was not dilated but had been displaced by the mass. (g) The coronal T1-weighted MR image showed encasement of the main portal vein (arrow) by the mass, which suggested the malignant features of the mass. (h) Photomicrograph (H & E, 400 ) of the specimen showed that the tumor cells had a trabacular pattern over the fibrotic and hyaline stroma. (i) The immunohistochemistry staining for synaptophysin ( 100) was positive which confirmed the diagnosis of malignant endocrine neoplasm of the pancreas

65 Se Woong Lim et al MRCP, despite the large size of the mass, the common bile duct was not dilated but was displaced by the mass (Fig. 1f). Coronal T1-weighted MR image of MR angiography showed encasement of the main portal vein by the mass (Fig. 1g), which suggested its malignant features in addition to the presence of metastatic lymphadenopathy. These CT and MRI findings were indicative of a primary malignant pancreatic neoplasm. Exploratory surgery revealed a large, hard mass in the pancreatic head and with conglomerated lymphadenopathy along the mesenteric root. As complete resection of the mass was not possible, metastatic lymph nodes were extracted. Microscopy of the specimens revealed that the tumor cells had a trabacular pattern over fibrotic and hyaline stroma (Fig. 1h). Immunohistochemistry staining revealed positive reaction for synaptophysin, neuronspecific enolase, Chromogranin A, and Pan CK, and was weakly positive for alpha-1-antipchymotrypsin (Fig. 1i). However, there were no detected endocrine substances including insulin, glucagon, and somatostatin. According to these results, the histopathologic diagnosis of the mass was well differentiated endocrine carcinoma of the pancreas, and the confirmative diagnosis of non-functioning, malignant pancreatic neuroendocrine tumor (PNET) was thus made. Discussion Pancreatic neoplasms are rarely seen in children. They can be divided into epithelial and nonepithelial types. Epithelial tumors may be further classified as exocrine or endocrine tumors. Exocrine tumors include acinar cell orign tumors i.e. pancreatoblastoma, acinar cell carcinoma; ductal cell orgin tumors, i.e. ductal cell adenocarcinoma; and undetermined cell origin tumors, i.e. solid-pseudopapillary tumor. Endocrine cell tumors are uncommonly encountered in older children, they can be functioning or nonfunctioning. Nonepithelial neoplasms, such as lymphoma or sarcoma, arising primarily in the pancreas are quite rare in children. Among these neoplasms, pancreatoblastoma and solidpseudopapillary tumors often occur in children and adolescents (1). When the imaging findings suggest malignant pancreatic tumor, pancreatoblastoma should not be ruled out in the differential diagnosis in infants and young children, as it is the most common childhood neoplasm. Pancreatoblastomas tend to be large, solitary tumors that most frequently arise from the pancreas body and/or tail or that involve the entire pancreas rather than usually being located in the pancreatic head. There may be direct extension to other abdominal organs, including the spleen, left kidney, and omentum. Hepatic metastasis, vascular encasement, and calcification are not uncommon (2). The other tumor that should be included in differential diagnosis of pancreatic tumor of children is solid pseudopapillary tumor. This tumor usually occurs in adolescent or young adult female. It is heterogeneous in internal architecture, with a complex mass of solid and cystic hemorrhagic and necrotic portions. The findings of fibrous capsule and internal hemorrhage are the features that can distinguish solid pseudopapillary tumor from other pancreatic tumors (3). Although malignant pancreatic neuroendocrine tumors are rarely seen in children, they should be included in the differential diagnosis when a malignant pancreatic mass is suspected. Among the endocrine tumors of the pancreas occurring in children, most cases of malignant endocrine tumors are found to be functioning endocrine tumors, such as malignant insulinoma or gastrinoma (4). Endocrine tumor of the pancreas can be associated with inherited disease processes such as multiple endocrine neoplasia (MEN type 1) and von Hippel-Lindau disease. As suggested by the recent studies that have reported the detection of only two cases of tuberous sclerosis complex in children (5, 6), there are very few reported studies of this tumor occurring in children. Nonfunctioning PNET is pathologically indistinguishable from functioning PNET, both of which are distinguished by the clinical or biochemical evidence of hormone hypersecretion. Widely accepted CT findings of nonfunctioning PNET include the following: a welldefined pancreatic mass of an unusually large size; moderate to strong enhancement seen on the arterial phase for either primary or hepatic metastases; wellenhanced lymph node enlargement; and frequent vascular encasement (7, 8). Differentiating benign from malignant PNET is not easy. Distinctions between benign and malignant

66 Non-Functioning, Malignant Pancreatic Neuroendocrine Tumor in a 16-Year-old Boy tumors can be made based on the tumor size, lymph node involvement, and the presence of distant metastasis. Tumors are also considered to be malignant if there is any histologic evidence of vascular, lymphatic or perineural invasion. On CT and MRI scans of our patient, the initial differential diagnosis of this tumor included pancreatoblastoma and malignant PNET due to its solid nature, the absence of cystic or necrotic portions, its heterogeneous enhancement pattern, lymph node metastasis, and the portal vein encasement. It has been reported that some pancreatic endocrine tumors show delayed contrast enhancement on dynamic CT, caused by the presence of tumor thrombi in the veins around the mass (9). Some researchers have reported that delayed phase T1-weighted MR imaging is useful for the detection of PNET, especially scirrhous type (10). In our case, the delayed phase of dynamic MRI showed persistent inhomogeneous enhancement of both the pancreatic mass and the metastatic lymph nodes. Considering this dynamic MR imaging findings, the diagnosis was closer to that of malignant PNET. The treatment of malignant PNET is primarily by surgical resection, especially for unmetastasized tumors; unfortunately, as surgical resection was not feasible in our case due to extensive peritoneal and retroperitoneal adhesion of tumor and metastatic lymphadenopathy, only biopsies of the mass and lymph node were performed. In conclusion, the imaging findings of malignant PNET in pediatric patients do not different from those of adult onset ones, as a solid pancreatic mass with malignant features such as vascular invasion, adhesion to adjascent organs or lymph node metastasis. The dynamic MR imaging might be useful in the differential diagnosis of malignant pancreatic tumors occurring in children. A larger number of reported cases, as well as analysis of malignant PNET will be needed in order to further advance our understanding of the imaging features of this tumor. References 1.Shorter NA, Glick RD, Klimstra DS, Brennan MF, LaQuaglia MP. Malignant pancreatic tumors in childhood and adolescence: the Memorial Sloan-Kettering experience, 1967 to present. J Pediatr Surg 2002;37: Roebuck DJ, Yuen MK, Wong YC, Shing MK, Lee CW, Li CK. Imaging features of pancreatoblastoma. Pediatr Radiol 2001;31: Chung EM, Travis MD, Conran RM. Pancreatic tumors in children: radiologic-pathologic correlation. Radiographics 2006;26: Grosfeld JL, Vane DW, Rescorla FJ, McGuire W, West KW. Pancreatic tumors in childhood: analysis of 13 cases. J Pediatr Surg 1990;25: Verhoef S, van Diemen-Steenvoorde R, Akkersdijk WL, Bax NM, Ariyurek Y, Hermans CJ, et al. Malignant pancreatic tumour within the spectrum of tuberous sclerosis complex in childhood. Eur J Pediatr 1999;158: Francalanci P, Diomedi-Camassei F, Purificato C, Santorelli FM, Giannotti A, Dominici C, et al. Malignant pancreatic endocrine tumor in a child with tuberous sclerosis. Am J Surg Pathol 2003;27: Procacci C, Carbognin G, Accordini S, Biasiutti C, Bicego E, Romano L, et al. Nonfunctioning endocrine tumors of the pancreas: possibilities of spiral CT characterization. Eur Radiol 2001;11: Stafford-Johnson DB, Francis IR, Eckhauser FE, Knol JA, Chang AE. Dual-phase helical CT of nonfunctioning islet cell tumors. J Comput Assist Tomogr 1998;22: Koito K, Namieno T, Nagakawa T, Morita K. Delayed enhancement of islet cell carcinoma on dynamic computed tomography: a sign of its malignancy. Abdom Imaging 1997;22: Ichikawa T, Peterson MS, Federle MP, Baron RL, Haradome H, Kawamori Y, et al. Islet cell tumor of the pancreas: biphasic CT versus MR imaging in tumor detection. Radiology 2000;216:

67 Se Woong Lim et al 대한자기공명의과학회지 14: (2010) 16 세남아에서발생한췌장의비기능성악성신경내분비종양 : 증례보고 1 원광대학교의과대학영상의학과 2 인제대학교상계백병원영상의학과 임세웅 1 이영환 1 최시성 1 조현선 2 소아에서췌장의악성종양은매우드물게발생하고있으며, 특히악성신경내분비종양은더더욱드물다. 저자들은 16세소아환자에서발생한비기능성악성신경내분비종양의증례를경험하여 CT와 MRI 소견을보고하고자한다. 췌장두부에서발생한고형종양으로조영증강 MRI의문맥기에서지연기로갈수록조영증강이잘되고, 주변의혈관침습, 총담관폐색, 림프절병증등악성소견을동반할때췌장의비기능성악성신경내분비종양을감별진단에포함하여야한다. 통신저자 : 이영환, ( ) 전북익산시신용동 344-2, 원광대학교병원영상의학과 Tel Fax yjyh@wonkwang.ac.kr

68 일차성간림프종 : 자기공명영상과병리소견의연관 김한나 1 신유리 1 나성은 1 정은선 2 오순남 1 최준일 1 정승은 1 이영준 1 일차성간림프종은전체림프절외장기를침범하는림프종의 1% 미만에서나타나는매우드문질환이다. 저자들은수술로확진된일차성간림프종의자기공명영상과병리소견의특징을보고한다. 간세포특이조영제를주입하여얻은역동적조영증강영상에서점차적으로조영증강되어간내담관암과유사하게보였다. 그러나 20분지연후얻은간담관기영상과확산강조영상에서서로다른신호강도를보이는세층의띠모양의병변이특징적으로보였으며이는병리적으로외층의생존종양, 중간층의괴사된종양, 및종양에둘러싸인중앙부의괴사된간실질과일치되는소견을보였다. 서 론 증례보고 일차성간림프종은비장, 림프절, 골수또는다른림프조직을침범하지않고, 간에국한되어있는림프종으로정의할수있다 (1). 간은진행된비호지킨림프종환자에서흔히침범하는림프절외장기의하나이지만대부분이차성간림프종이며, 일차성간림프종은매우드물다. 간림프종의영상진단은, 이차성인경우동반된다른소견과함께고려할때비교적쉽게진단할수있으나, 일차성의경우그다양한발현양상과드문빈도로인해영상소견이잘정리되어보고되지않아영상진단에어려움을겪는경우가흔하다 (2, 3). 일차성간림프종의자기공명영상소견은거의보고되지않았는데, 저자들은최근단일종괴로발현하였으며간표면위축을동반하였고, 역동적조영증강소견등을고려할때간내담관암을의심할수있었던일차성간림프종을경험하였다. 특히본증례에서는간세포특이조영제를이용한자기공명영상및확산강조자기공명영상에서림프종의병리소견을잘설명할수있는특징적인영상소견을확인할수있었기에이를보고하고자한다. 78세남자환자가 2개월간의우상복부통증으로입원하였다. 환자는체중감소나야간발한등은없었다. 환자는과거력에서특이소견이나간경변을시사하는소견은없었으며비장이나림프절이촉지되지않았다. 혈액검사결과는젖산탈수소효소가경미하게증가된것이외에정상이었고혈청검사결과 A형, B형그리고 C형간염검사가모두음성이었으며태아성암항원 (CEA), 알파태아단백 (alpha-fetoprotein), 당쇄항원 19-9(CA 19-9) 를포함한종양표지검사도모두정상범위였다. 복부초음파검사에서는간에크기약 6 cm의크고불균질한에코를보이는종괴가보였다. 역동적조영증강전산화단층촬영에서는큰고형의저감쇠를보이는종괴가간좌엽에있고동맥기와문맥기에서는주변부가조영증강되고평형기로갈수록중심부에점차조영증강이되는양상을보였다. 간피막의퇴축이동반되어있었다. 자기공명영상 (Achieva 1.5T, Philips medical systems, Best, The Netherlands) 에서는간좌엽에분엽상의큰종괴가보이고간원삭틈새와좌문맥의배꼽분절을둘러싸고있으나종괴에의한간문맥과간원삭틈새의폐쇄는보이 대한자기공명의과학회지 14: (2010) 1 가톨릭대학교의과대학방사선과학교실서울성모병원영상의학과 2 가톨릭대학교의과대학병원병리학교실서울성모병원접수 : 2010 년 10 월 5 일, 수정 : 2010 년 10 월 10 일, 채택 : 2010 년 10 월 14 일통신저자 : 신유리, ( ) 서울특별시서초구반포동 505 번지, 가톨릭대학교의과대학방사선과학교실서울성모병원영상의학과 Tel. (02) Fax. (02) crystal57@catholic.ac.kr

69 김한나외 a b c d Fig. 1. A 78-year-old man with primary hepatic lymphoma. (a) Axial fat suppressed T2-weighted fast spin echo image shows a large lobulated hyperintense mass (arrows) in the left hepatic lobe. (b) Coronal T2-weighted single shot fast spin echo image shows a large lobulated heterogeneous hyperintense mass (arrows), surrounding the fissure for ligamentum teres (arrowhead). (c) Axial pre-contrast T1-weighted image shows hypointense mass (arrow) in the left hepatic lobe. (d, e) Axial portal venous (d) and equilibrium (e) phase contrast-enhanced T1-weighted image show poor, heterogeneous enhancement of the mass (arrow). Progressive enhancement is seen in the central portion of the mass. e

70 일차성간림프종 f g h j i Fig. 1. (f) Axial 20 minute-delayed hepatobiliary phase contrast-enhanced T1-weighted image clearly shows two different signal intensity of the lesion: lymphoma with very low signal intensity area (arrow) and slightly low signal intensity entrapped by the tumor with necrotic hepatic parenchyma (dotted arrow). (g) Axial diffusion-weighed image (b = 800) shows three different signal intensity of the lesion: a bandlike high signal intensity of the tumor (arrow), thin linear dark signal intensity along the medial margin of the high signal intensity (arrowhead), consistent with necrotic tumor, and intermediate signal intensity area (dotted arrow) entrapped by the tumor consistent with necrotic hepatic parenchyma. (h) F-18 FDG PET-CT shows a band-like hot uptake showing the same configuration with that of diffusion-weighted image, suggestive of a viable tumor. (i) Gross specimen shows three different zones consisting of a bandlike lobulated tumor (arrow), focal tumoral necrosis (arrowhead), and necrotic hepatic parenchyma without tumor involvement (dotted arrow). (j) Photomicrography of specimen (immunohistochemical staining for CD20, 400) shows multiple large atypical lymphoid cells expressing CD20, consistent with diffuse large B-cell lymphoma

71 김한나외 지않았고비정상적인담관확장도없었다. 종괴는지방억제고속스핀에코 T2 강조영상 (TR/TE=2855/80 msec) 에서는불균질한고신호강도로보였고 (Fig. 1a, b) 고속경사에코 T1 강조영상 (TR/TE=240/4.6 msec, Flip angle 80 ) 에서저신호강도로보였다 (Fig. 1c). 지방억제호흡정지 3D 경사에코 (THRIVE, TR/TE = 4.4/2.1 msec, Flip angle 15, echo train 60, Matrix , NEX 1.0, section thickness/gap 4.0 mm/2.0 mm) 를이용한역동적조영증강검사를시행하였으며신체중량의 kg당 mmol의 gadoxetic acid (Gd-EOB-DTPA; Primovist, Bayer-Schering pharma, Berlin, Germany) 를주사한후 30 ml의식염수를신속주입하였다. 종괴는동맥기에서는조영증강을거의보이지않았으며문맥기와평형기에는회오리모양으로간실질보다낮게조영증강되었다 (Fig. 1d, e). 조영증강 20분후에얻은간담관기에서종괴의가장자리부분은더낮은저신호강도를보이고중심부는덜낮은신호강도를보였다 (Fig. 1f). 확산강조영상 (b=800) 에서종괴주변부는회오리모양의밴드양상의고신호강도를보였으며그내측에얇은띠모양의매우낮은신호강도를보이는부분이있었고중심부는정상간실질과등신호강도를보였다 (Fig. 1g). 양전자방출단층촬영 (F-18 FDG PET- CT) 에서종괴는주변부에확산강조영상과비슷한밴드양상의강한신호를보이는고대사성병변으로보였고중심부는섭취결손을보였다 (Fig. 1h). 종괴의수술전진단은간내담관암으로생각하였다. 환자는좌간절제술을시행하였으며수술소견은황백색의단단한종괴였고변연은잘국한된분엽상을보였다 (Fig. 1i). 병리소견에서는미만성대세포림프종으로확진되었다 (Fig. 1j). 자기공명영상소견과병리소견을연관하여보면확산강조영상에서주변부에고신호로보였던부분은살아있는림프종세포가있는부위이며그내측으로띠모양의매우낮은신호강도를보이는부분은괴사였고내부에정상간과등신호강도를보인부분은암세포가아닌죽은간세포부위였다. 간담관기영상에서도림프종부위는매우저신호강도를보였으나중심부의죽은간세포부위는약간저신호강도를보였다 (Fig. 1f, g, i). 고찰간은림프종이자주침범하는대표적인림프절외장기로알려져있으나, 간을침범하는림프종은대부분간외림프종으로시작된이차성림프종이다. 간에서기원하는일차성림프종은매우드물어서전세계적으로 100예미만이보고되어있다 (4). 간림프종의영상소견은다양하게보고되었는데크게단일성종괴, 다발성종괴, 침윤성병변의세가지양상으로구분할수있다 (4-6). 이차성간림프종은간외침범이동반되므로영상의학적진단이어렵지않으나, 일차성간림프종중특히단일성종괴로발현하는경우다른간내원발암과의감별이어려워대부분의일차성간림프종의경우수술후확진된다 (7). 하지만림 프종은항암화학요법으로치료하는질환이므로영상의학적으로간림프종을의심하고영상유도하조직검사를하여정확한진단하는것이불필요한수술을피하는데많은도움이된다. 간림프종은초음파검사에서대부분저에코의종괴로보이며, CT에서는거의대부분정상간실질보다낮은음영으로보인다 (6). 조영증강후 CT에서간림프종은대부분간실질보다낮은균일한조영증강을보이며일부에서는반점형조영증강또는고리모양의조영증강양상을보인다 (5, 6). 자기공명영상에서 T1 강조영상에서저신호강도로, T2 강조영상에서는고신호강도로보여, 간림프종의영상소견은특징적인점이없다 (4-6). 또한최근이용이증가하고있는간세포특이조영제를이용한간담관기영상이나확산강조영상소견은보고된바없다. 본증례는좌문맥의배꼽분절을둘러싸는커다란종괴로발견되었고역동적조영증강 CT 및자기공명영상에서시간이지날수록종양중심부의조영증강이강화되는소견과간표면퇴축이동반되어간내담관암을의심하여수술을시행하였으나병리학적으로림프종으로확진되었다. 후향적으로영상소견을분석해보면상당히큰종괴임에도불구하고주변담관확장이동반되지않았고, 종괴의중심부에위치한문맥과간원삭틈새주변의지방층이폐색되지않고잘유지되어있는점등이간내담관암의영상소견과는다른점이라생각된다. 또한간표면퇴축으로판단하였던소견은종괴가중심에위치한문맥및간원삭틈새주변을보존하며자라나서주위간표면을불룩하게만들어생긴이차적인현상으로생각된다. 본증례의흥미로운점은확산강조영상과간담관기조영증강영상소견이육안병리소견과잘일치하는점인데생존종양부위와괴사부위, 또한종양의중심부에위치했던괴사에빠진정상간이서로다른세층의신호강도로구분되어보였다. 림프종은일반적으로주변혈관이나장기의형태를유지하며자라는것이특징인데본증례에서도종괴의중심부에위치한문맥과간원삭틈새주변의지방층이잘유지되었으며이런병리학적소견이확산강조영상과간담관기조영증강영상소견에서잘반영되어보였다. 또한미만성대세포림프종은항암치료를받지않아도림프종자체에괴사부위가생길수있는데이런병리학적소견도영상소견에서잘반영되어보였다 (8). 이런소견들은간내담관암과의감별진단에도움이될것으로생각되며, 간종괴에대한자기공명영상시간세포특이조영제를이용하고확산강조영상을추가하는것이감별진단에도움이될것으로기대된다. 결론적으로본증례는매우드문일차성간림프종으로고식적자기공명영상에서간내담관암과유사하여감별이어려웠으나, 종양의범위와병리학적특징을간세포특이조영제를이용한간담관기영상과확산강조영상이잘반영하므로이들기법의추가가간내종괴평가에도움이되었던증례이다

72 일차성간림프종 참고문헌 1.Peixoto MCG, Filho AAA, Ribeiro ACR, D lppolito G. Non- Hodgkin s lymphoma presenting as a single liver mass. Radiol Bras 2009;42: Miyamoto Y, Izuo M, Ikeya T, et al. Right hepatic lobectomy for primary lymphoma: a case report and literature review. Jpn J Surg 1986;16: Ryan J, Straus DJ, Lange C, et al. Primary lymphoma of the liver. Cancer 1988;61: Noronha V, Shafi NQ, Obando JA, Kummar S. Primary non- Hodgkin s lymphoma of the liver. Crit Rev Oncol hematol 2005;53: Maher MM, McDermott SR, Fenlon HM, et al. Imaging of primary non-hodgkin s lymphoma of the liver. Clin Radiol 2001;56: Gazelle GS, Lee MJ, Hahn PF, Goldberg MA, Rafaat N, Mueller PR. US, CT, and MRI of primary and secondary liver lymphoma. J Comput Assist Tomogr 1994;18: Doi H, Horiike N, Hiraoka A, et al. Primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type: case report and review of the literature. Int J Hematol 2008; 88: Juan Rosai. Rosai and Ackerman s surgical pathology, 9th ed. Mosby edinburg : J. Korean Soc. Magn. Reson. Med. 14: (2010) Primary Hepatic Lymphoma: MR Imaging and Pathologic Correlation Hanna Kim 1, Yu Ri Shin 1, Sung Eun Rha 1, Eun Sun Jung 2, Soon Nam Oh 1, Joon-Il Choi 1, Seung Eun Jung 1, Young Joon Lee 1 1 Department of Radiology, Seoul St. Mary s Hospital, College of Medicine, The Catholic University of Korea 2 Department of Hospital Pathology, Seoul St. Mary s Hospital, College of Medicine, The Catholic University of Korea Primary hepatic lymphoma is extremely rare, representing less than 1% of all extranodal lymphomas. We report MR imaging features and pathologic correlation of a case of primary hepatic lymphoma. MR images showed a large lobulated mass with gradual contrast enhancement, resembling intrahepatic cholangiocarcinoma. However, both hepatobiliary phase image obtained 20 minutes after injection of hepatocyte specific contrast agent and diffusion-weighted image demonstrated characteristic three layered pattern representing viable lymphoma in the outer layer, tumor necrosis in the middle layer and necrotic hepatic parenchyma in the center. Index words : Lymphoma Liver Magnetic resonance imaging (MRI) Address reprint requests to : Yu Ri Shin, M.D., Department of Radiology, Seoul St. Mary s Hospital, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul , Korea. Tel Fax crystal57@catholic.ac.kr

73 일차성간림프종 : 자기공명영상과병리소견의연관 김한나 1 신유리 1 나성은 1 정은선 2 오순남 1 최준일 1 정승은 1 이영준 1 일차성간림프종은전체림프절외장기를침범하는림프종의 1% 미만에서나타나는매우드문질환이다. 저자들은수술로확진된일차성간림프종의자기공명영상과병리소견의특징을보고한다. 간세포특이조영제를주입하여얻은역동적조영증강영상에서점차적으로조영증강되어간내담관암과유사하게보였다. 그러나 20분지연후얻은간담관기영상과확산강조영상에서서로다른신호강도를보이는세층의띠모양의병변이특징적으로보였으며이는병리적으로외층의생존종양, 중간층의괴사된종양, 및종양에둘러싸인중앙부의괴사된간실질과일치되는소견을보였다. 서 론 증례보고 일차성간림프종은비장, 림프절, 골수또는다른림프조직을침범하지않고, 간에국한되어있는림프종으로정의할수있다 (1). 간은진행된비호지킨림프종환자에서흔히침범하는림프절외장기의하나이지만대부분이차성간림프종이며, 일차성간림프종은매우드물다. 간림프종의영상진단은, 이차성인경우동반된다른소견과함께고려할때비교적쉽게진단할수있으나, 일차성의경우그다양한발현양상과드문빈도로인해영상소견이잘정리되어보고되지않아영상진단에어려움을겪는경우가흔하다 (2, 3). 일차성간림프종의자기공명영상소견은거의보고되지않았는데, 저자들은최근단일종괴로발현하였으며간표면위축을동반하였고, 역동적조영증강소견등을고려할때간내담관암을의심할수있었던일차성간림프종을경험하였다. 특히본증례에서는간세포특이조영제를이용한자기공명영상및확산강조자기공명영상에서림프종의병리소견을잘설명할수있는특징적인영상소견을확인할수있었기에이를보고하고자한다. 78세남자환자가 2개월간의우상복부통증으로입원하였다. 환자는체중감소나야간발한등은없었다. 환자는과거력에서특이소견이나간경변을시사하는소견은없었으며비장이나림프절이촉지되지않았다. 혈액검사결과는젖산탈수소효소가경미하게증가된것이외에정상이었고혈청검사결과 A형, B형그리고 C형간염검사가모두음성이었으며태아성암항원 (CEA), 알파태아단백 (alpha-fetoprotein), 당쇄항원 19-9(CA 19-9) 를포함한종양표지검사도모두정상범위였다. 복부초음파검사에서는간에크기약 6 cm의크고불균질한에코를보이는종괴가보였다. 역동적조영증강전산화단층촬영에서는큰고형의저감쇠를보이는종괴가간좌엽에있고동맥기와문맥기에서는주변부가조영증강되고평형기로갈수록중심부에점차조영증강이되는양상을보였다. 간피막의퇴축이동반되어있었다. 자기공명영상 (Achieva 1.5T, Philips medical systems, Best, The Netherlands) 에서는간좌엽에분엽상의큰종괴가보이고간원삭틈새와좌문맥의배꼽분절을둘러싸고있으나종괴에의한간문맥과간원삭틈새의폐쇄는보이 대한자기공명의과학회지 14: (2010) 1 가톨릭대학교의과대학방사선과학교실서울성모병원영상의학과 2 가톨릭대학교의과대학병원병리학교실서울성모병원접수 : 2010 년 10 월 5 일, 수정 : 2010 년 10 월 10 일, 채택 : 2010 년 10 월 14 일통신저자 : 신유리, ( ) 서울특별시서초구반포동 505 번지, 가톨릭대학교의과대학방사선과학교실서울성모병원영상의학과 Tel. (02) Fax. (02) crystal57@catholic.ac.kr

74 김한나외 a b c d Fig. 1. A 78-year-old man with primary hepatic lymphoma. (a) Axial fat suppressed T2-weighted fast spin echo image shows a large lobulated hyperintense mass (arrows) in the left hepatic lobe. (b) Coronal T2-weighted single shot fast spin echo image shows a large lobulated heterogeneous hyperintense mass (arrows), surrounding the fissure for ligamentum teres (arrowhead). (c) Axial pre-contrast T1-weighted image shows hypointense mass (arrow) in the left hepatic lobe. (d, e) Axial portal venous (d) and equilibrium (e) phase contrast-enhanced T1-weighted image show poor, heterogeneous enhancement of the mass (arrow). Progressive enhancement is seen in the central portion of the mass. e

75 일차성간림프종 f g h j i Fig. 1. (f) Axial 20 minute-delayed hepatobiliary phase contrast-enhanced T1-weighted image clearly shows two different signal intensity of the lesion: lymphoma with very low signal intensity area (arrow) and slightly low signal intensity entrapped by the tumor with necrotic hepatic parenchyma (dotted arrow). (g) Axial diffusion-weighed image (b = 800) shows three different signal intensity of the lesion: a bandlike high signal intensity of the tumor (arrow), thin linear dark signal intensity along the medial margin of the high signal intensity (arrowhead), consistent with necrotic tumor, and intermediate signal intensity area (dotted arrow) entrapped by the tumor consistent with necrotic hepatic parenchyma. (h) F-18 FDG PET-CT shows a band-like hot uptake showing the same configuration with that of diffusion-weighted image, suggestive of a viable tumor. (i) Gross specimen shows three different zones consisting of a bandlike lobulated tumor (arrow), focal tumoral necrosis (arrowhead), and necrotic hepatic parenchyma without tumor involvement (dotted arrow). (j) Photomicrography of specimen (immunohistochemical staining for CD20, 400) shows multiple large atypical lymphoid cells expressing CD20, consistent with diffuse large B-cell lymphoma