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1 J Korean Balance Soc 2008;7(2): 메니에르병환자에서고실내 Gadolinium-diethylen -triamine pentaacetic acid 주입후자기공명영상을통한내림프공간의시각화 연세대학교의과대학이비인후과학교실 1, 영상의학교실 2 서영준 1, 심대보 1, 김진아 2, 이원상 1 Visualization of endolymphatic hydrops using Magnetic Resonance Imaging after intratympanic Gd-DTPA administration in patients with Meniere s disease Young Joon Seo, MD 1, Dae Bo Shim, MD 1, Jinna Kim, MD 2, Won Sang Lee, MD 1 Departments of 1 Otorhinolaryngology and 2 Radiology, Yonsei University College of Medicine, Seoul, Korea Background and Objectives: Endolymphatic hydrops are known as major causes of Meniere s disease. MRI (Magnetic resonance imaging) with contrast tried recently makes it possible to visualize perilymphatic and endolymphatic space without invasive procedures. There are no tryouts in the interior of our country. We attempted MRI after injection of gadolinium-diethylen triamine pentaacetic acid (Gd-DTPA) in normal adults and patients with Meniere s disease to make sure 3D-FLAIR (fluid-attenuated inversion recovery) MRI parameters and to visualize endolymphatic spaces. Materials and Methods: Five normal adults and Five patients with Meniere s disease were included in this study. Twenty-four hours after Gd-DTPA intratympanic injection, we performed 3D-FLAIR and 3D-IR imaging at 3T. MRI region of interest signal intensity was used to determine the diffusion of Gd-DTPA into the perilymphatic fluid spaces over time. Results: Five of five in normal group, using 3D-IR MRI after Gd injection, had enhanced imagings (perilymphatic spaces) of inner ears. Five of five in patients group, using 3D-IR after Gd injection, had enhanced perilymphatic spaces and non-enhanced endolymphatic hydrops. Conclusions: Delayed contrast imaging of the inner ear with 3D-IR MRI after Gd-DTPA intratympanic injection revealed in vivo visualization of endolymphatic hydrops. Key words: Endolymphatic hydrops, 3D-FLAIR MRI, Gd-DTPA, Intratympanic injection Address for correspondence: Won Sang Lee, MD Departments of Otorhinolaryngology, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul , Korea Tel: , Fax: wsleemd@yuhs.ac 서론 메니에르병은반복적인어지럼증과청력장애, 이 167

2 메니에르병환자에서고실내 Gd-DTPA 주입후자기공명영상을통한내림프공간의시각화 명, 이충만감을특징으로하는질환으로그원인은아직확실히밝혀져있지않으나, 현재까지내림프액의과도한생성혹은흡수장애로인한내림프수종 (endolymphatic hydrops) 이발병기전으로제시되고있다. 1 메니에르병은유병률이높은반면진단은환자의증상에대부분의존하며아직객관적인진단방법이미미한실정이다. 2 이에대한영상학적평가가가능하다면환자를진단하는데에도큰도움이될뿐만아니라, 치료대상과방법을선정하며재발의예측인자를평가하는데도큰도움이될것이다. 최근에고자장자기공명영상 (High resolution magnetic resonance imaging; MR imaging) 을이용하여내림프액공간을영상화하고자하는연구들이진행되고있으며이들은 MR 조영제인 Gd-DTPA (gadoliniumdiethylen triamine pentaacetic acid) 를고실내에주입하여외림프액만을선택적으로조영증강시킴으로써상대적으로조영증강이되지않는내림프액공간의영상을얻고있다. 3-6 저자들은아직국내에서는시도되지않았던자기공명영상기법을이용하여내이에질병이없는정상성인과메니에르병환자에서고실을통한 Gd-DTPA 주입후고자장자기공명영상을이용하여내이의내림프액공간을비교해봄으로써내림프수종을시각화할수있는지에대한연구를진행하였으며이를문헌고찰과함께보고하는바이다. 대상및방법 대상피실험자는외이도및중이, 내이에질병이없는건강한성인 5명과본원에서메니에르병으로진단및치료받는 5명의환자들을선정하여실험하였다. 정상군의대상피실험자들은각각질병과거력, 어지럼, 청력, 고막상태등에대해이비인후과전문의 2명에의해이중선별검사를받았으며모두특별한이상을보이지않았다. 정상군의평균연령은연령은 24~34세까지였으며, 평균연령은 25.5±3.78세, 남녀비는 4:1이었으며모두좌측에조영제를주입하였다. 실험환자군은병력과청각및전정기능검사를통해일측성이며, 명확한 (definte) 메니에르병으로진단되고, 이과적수술치료를받지않은환자로, 현재보존치료에도불구하고지속적으로어지럼및청각장애, 이명, 이충만감증상을가지는환자 5명을대상으로 Gd- DTPA 고실내주입이후에 3T IR (inversion-recovery) MRI를촬영하였다. 연령은 32세부터 57세까지였으며, 평균연령은 49.7±5.83세, 남녀비는 3:2였다. 메니에르병의진단은 AAO-HNS (1995) 의진단기준을이용하였고양측성메니에르병이의심되거나진단된환자는연구에서제외하였다. 이실험에참가한피실험자들에게모두서문으로된동의서를받았으며, 이연구는본원에서임상시험심사위원회 (Institutional review board; IRB) 의승인을얻어시행하였다. Gd-DTPA 조영제 (Omniscan, GE healthcare AS, Oslo, Norway) 를생리식염수와 1:7로희석하여사용하였으며, 23게이지바늘을이용하여 1 ml 주사기에담아주입하였다. 피실험자는천장을보고누운채로머리를시상면에서실험할귀의반대측으로약 30 기울인후통증을줄이기위해피실험자의귀에마취연고 (emla 5% cream) 를바르고 30분뒤에조영제를주입하였다. 동일한한명의이비인후과전문의가희석된조영제를고막천자를통해고실로주입하였으며외이도로조영제가흘러나올때까지주입하였고평균주입양은 0.3~0.6 ml였다. 주입후에피실험자는시상면에서실험한귀의반대측으로머리를 60 기울여서누운채 60분간정원창을통해조영제가충분히흡수되도록기다렸다. 3T 자기공명영상장치 (Magnetom Trio, Siemens, Erlangen, Germany) 에서 receive-only 12-channel phasedarray coil을이용하여영상을얻었으며영상은조영제의고실내주입 24시간후에획득하였다. 내이미로의해부학적구조와림프액을확인하기위해 fast spinecho (FSE) T2 강조영상을얻은후내림프액과외림프액공간을구분하기위해 3D-FLAIR 및 3D IR turbo spin-echo (TSE) 영상을얻었다. 사용된 parameter는다음과같다 ; TR (repetition time), 9,000 ms; TE (effective echo time), 128 ms; TI (inversion time), 2,500 ms, 1700 ms; flip angle, 180 (constant) for the turbo spin-echo refocusing echo-train; echo-train length, 23; matrix size, ; 12 axial 2-mm-thick sections covering the labyrinth with a 16-cm square FOV acquired with use of the generalized autocalibrating partially parallel acquisition parallel imaging technique with an acceleration factor of 2; NEX, 1, and scan time, 14 minutes. 3D- FLAIR 및 IR로획득한영상은영상의학과전문의가 168

서영준외 3 인 A B Fig. 1. Perilymphatic spaces were enhanced in 3D-IR MRI after Gd-DTPA intratympanic injection in normal adults. (A) in cochlea, all turns seen well enhanced diffusely.

In normal group, 1 person had non-enhanced space (arrow) but he had no symptoms of Meniere s disease. We suppose that he had idiopathic endolymphatic hydrop visualized.

3 서영준외 3 인 A B Fig. 1. Perilymphatic spaces were enhanced in 3D-IR MRI after Gd-DTPA intratympanic injection in normal adults. (A) in cochlea, all turns seen well enhanced diffusely. (B) in vestibule and semicircular canals, well enhanced. Endolymphatic spaces non-enahanced were not seen in all normal adults. Fig. 2. In normal group, 1 person had non-enhanced space (arrow) but he had no symptoms of Meniere s disease. We suppose that he had idiopathic endolymphatic hydrop visualized. 분석하였으며, 피실험자들은 1달간외래에서추적관찰하였고실험전과동일한이학적검사가이루어졌다. 결과 10명의피실험자들에서 Gd-DTPA를고실내에주입하는동안피실험자들은특별한증상을호소하지않았으며외래추적관찰에서도고막은정상적으로 healing 되었으며다른이상소견은보이지않았다. 모든 5명의정상군에서조영제를주입한좌측내이에서외림프액공간들의조영증강을확인할수있었 으며, 조영제는달팽이관, 전정기관, 반고리관의모든외림프액공간에서확인할수있었다 (Fig. 1A,B). 5명중 4명의환자에서는조영결손을보이는부위가없어내림프액공간을확인할수없었으나, 1명의환자에서달팽이관의기저회전에서내림프액공간으로생각되는조영결손부위를발견하였다 (Fig. 2). 명확한메니에르병으로진단된 5명의환자에서 Gd-DTPA 조영제주입후에촬영한 3D-IR MRI에서 5명모두에서외림프액의조영증강을확인할수있었으며, 5명중 1 명 (20%) 에서만세반고리관에서외림프액공간을확인할수없었으며, 그외외림프액공간은모두조영 169

After Gd-DTPA intratympanic injection, 3D-IR MRI (A) T2-weighted image shows membraneous labyrinth high signals. (B) T1-weighted image after Gd-DTPA enhanced.

4 메니에르병환자에서고실내 Gd-DTPA 주입후자기공명영상을통한내림프공간의시각화 A B Fig. 3. Endolymphtaic hydrops well visualized and enhanced perilymphatic spaces seen surrounding endolymphatic spaces in left side of a definite Meniere s disease patient. After Gd-DTPA intratympanic injection, 3D-IR MRI (A) T2-weighted image shows membraneous labyrinth high signals. (B) T1-weighted image after Gd-DTPA enhanced. all cochlear turns had endolymphatic hydrops (arrow). A B Fig definite Meniere s disease patients had all endolymphatic hydrops partial or whole turns of cochlea. Those patients had non-enhanced area, endolymphatic spaces in different areas of cochlea (A, B). 증강되어시각적으로확인할수있었다. 5명의메니에르병환자들에서 5명모두 (100%) 에서달팽이관에서내림프수종으로생각되는내림프액결손이보였으며 (Fig. 3A,B), 달팽이관의모든회전에서조영결손을보이는환자는 3 (60%) 명, 기저회전에서만결손을보이는환자는 4 (80%) 명, 첨단회전에서조영결손을보이지않는경우가 2 (40%) 명있었다 (Fig. 4A,B). 구형낭과타원낭모두에서조영결손을보이는경우는 1 (20%) 이었으며, 세반고리관에서내림프액결손을보이는경우는없었다. 고찰재발성어지럼, 청력저하, 이명, 이충만감을특징으 로하는내이질환인메니에르병이라는명칭은프랑스의사인 Prosper Meniere (1799~1862) 2 의이름에서유래된것이다. 1995년 AAO-HSN에서제시한메니에르병의정의 7 는원인불명의 내림프수종 이다. 원인불명이라는것은존재하지않는다는것이아니라아직까지정확히알려진것이없다는뜻이다. 메니에르병은전체어지럼환자의약 10% 정도인고빈도를보이는내이질환중한가지이지만메니에르병의증상들을일으킨다고알려져있는내림프수종을진단하는데에객관적인방법이없다. 이때문에대부분의이비인후과의사들이환자의주관적인증상으로병의경중을논하며, 진단및치료를시행하고있다. 8 고자장의 MRI를이용하여내이의외림프액공간과내림프액공간을구분한연구는그동안많은진척이 170

서영준외 3 인 Fig. 5. Acase of a left sided definite Meniere s disease patient. He had symptoms of left hearing loss proved in PTA, recurrent spinning vertigo over 20 minutes, tinnitus and earfullness.

5 서영준외 3 인 Fig. 5. Acase of a left sided definite Meniere s disease patient. He had symptoms of left hearing loss proved in PTA, recurrent spinning vertigo over 20 minutes, tinnitus and earfullness. Dilated vestibular hydrops lesion (arrow) might block the flow of Gd-DTPA into semicircular canals non-enhanced. Left sided abnormal VEMP (vestibular evoked myogenic potential) meaning left saccular dysfunction was showed. 있었다. 동물실험을통하여전정계, 중간계, 고실계를구분하여해부학적소견과비교를통하여정확한상관관계를구분 9 했을뿐만아니라, 고자기장에영향을받지않는카데바 10 를 Gd-DTPA 주입후에 7T 자기장안에서촬영하여역시내이의해부학적구조를영상학적으로시각화하는데성공하였다. 하지만고자기장하에서환자들을촬영하기위해서는위험성이높아촬영에한계가있었고, Gd-DTPA 주입방법및주입후촬영까지걸리는시간등이정립이되지않아환자들을대상으로연구가이루어지지않았다. 이후 Zour 11 등은고실내로조영제를주입하면고실의정원창을통하여고실계 (scala tympnai) 를통해우선약물이확산되고, 이어전정계 (scala vestibule) 로확산되어외림프액이조영증강된다는것을알아내었다. 15,16 Naganawa S 등은 Gd-DTPA 조영제의주입방법과확산되는시간등에대한방법들을연구하였을뿐만아니라 3T 자기장하에 3D FLAIR MRI를이용하여보다선명하게내림프수종의존재를시각적으로증명하였다. 본연구는내림프수종이메니에르병을가진환자의내이에서특징적인소견이라는가정하에인체에서 3T MRI를촬영하여내림프수종의존재를보고한방법들을참고하여본원이비인후과에내원하는정상인들과메니에르병을가진환자들을대상으로동의를얻은후임상시험심사위원회의승인하에시행하였다. 실험을진행하는동안침습적인방법으로인하여환자에게청력감소, 어지럼악화등특별한문제점들은발견되지않았으며, 실험종료한달째까지검사에따 171

6 메니에르병환자에서고실내 Gd-DTPA 주입후자기공명영상을통한내림프공간의시각화 른문제는발생하지않았다. 본연구는건강한정상성인 5명과일관된그룹특성을가진명확한메니에르병그룹환자 5명을대상으로이루어졌다는데의의가있다. 정상성인들을대상으로우선적인실험을거쳐정상인의내이에서내림프공간을시각적으로알아보려고하였으며, 이를기초로실험군의메니에르병환자와비교하여내림프수종의상대적이고객관적인측정이가능한지알아보려고하였다. 또한이전보고연구들에서는실험군의설정의기준이모호하였으나, 본연구에서는 AAO- HSN 에서제시한메니에르병의분류에입각하여명확한메니에르병그룹에속한환자들만을선택적으로실험, 실험군간의동질성을높여보다객관적인실험이이루어지도록하였다. 정상성인에서내림프액공간은보이지않았으며, 이는내림프수종이없는정상내림프액공간이미미해서 3T MRI에서외림프액공간과구분이되지않을것으로생각된다. 한명의대조군에서내림프액공간을의심할만한조영결손이달팽이관의기저회전에서발견되었으나실험군의조영결손부위와비교하였을때, 그크기가상대적으로작고기저회전의확장소견이보이지않으며, 메니에르병의증상이없는정상성인에서도내림프수종이발견된다는사실로미루어보아특발성의 (idiopathic) 내림프수종으로생각된다. 이에반하여, 실험군에서는대조군에서보이지않았던조영결손부위가모든환자에서명확히확인할수있었다. 전정기관이하 ( 세반고리관 ) 의림프액공간에서조영증강이되지않은환자들이 1명있는데, 이는난형낭과구형낭부위의내림프수종을다른환자들과비교하였을때상당히큰것으로보아심하게확장된내림프수종이외림프액공간을막아 Gd-DTPA 조영제가확산되지못했을것으로사료된다 (Fig. 5). 17,18 이연구의가장큰한계점은비록다른연구들에비해많은환자군을대상으로실험을시행하여유의한결과를추론하였지만통계적으로유의한결과를이끌어내기에여전히부족한환자군을가지고있으며, 앞으로보다많은환자군의설정이필요할것이다. 영상학적으로뚜렷한조영결손부위를확인할수있었지만이는영상적으로결손부위, 즉음성적인소견이기때문에이부위를다른조영결손부위들 ( 뼈, 공기등 ) 과구분될수있는양성적인소견 (positive finding) 이필요할것이다. 현재증상이있는급성기의메니에르병을가진환자들에서이실험을시행하였기에만성기혹은무증상기의환자들의대상들과영상학적특징들의비교분석이이루어져야할것이며, 내림프수종을보일수있는급성난청환자, 전형적인어지럼증만있는환자등다른메니에르병분류의환자들과의비교분석이필요할것이다. 결론 본논문에서내이의내림프액공간과외림프액공간을구분하기위해 3D-IR MRI와 Gd-DTPA 조영제주입에대한방법들을확인하였으며, 정상성인의대조군과명확한메니에르병을가진환자군의비교분석을통하여내이의내림프수종을시각화하는데성공하였다. 이러한연구를바탕으로앞으로메니에르병이의심되는환자들에게보다정확한진단과치료가이루어지게될것으로믿는다. REFERENCES 1. Hallpike CS, Cairns H. Observations on the pathology of Meniere s syndrome. J Laryngol Otol 1938;53: Andrews JC, Honrubia V, Baloh RW, Halmagyi GM. Disorders of the Vestibular System. New York: Oxford University Press; 1996; Hans P, Grant AJ, Laitt RD, Ramsden RT, Kassner A, Jackson A. Comparison of three-dimensional visualization techniques for depicting the scala vestibuli and scala tympani of the cochlea by using high-resolution MR imaging. AJNR Am J Neuroradiol 1999;20: Silver RD, Djalilian HR, Levine SC, Rimell FL. Highresolution magnetic resonance imaging of human cochlea. Laryngoscope 2002;112: Nakashima T, Naganawa S, Sugiura M, Teranishi M, Sone M, Hayashi H, et al. Visualization of endolymphatic hydrops in patients with Meniere s disease. Laryngoscope 2007;117: Niyazov DM, Andrews JC, Strelioff D, Sinha S, Lufkin R. Diagnosis of endolymphatic hydrops in vivo with magnetic resonance imaging. Otol Neurotol 2001;22: Edwin MM, Thomas AB, George AG, Robert AG, William LM, John WH. Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation 172

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Microsoft Word doc KISEP Otology Korean J Otolaryngol 2006;49:7-12 돌발성난청환자에서촬영한자기공명영상의진단적유용성 안중호 1 이정현 2 여남경 1 배기훈 1 윤태현 1 이광선 1 정종우 1 The Diagnostic Value of Magnetic Resonance Imaging in Patients with Sudden Sensorineural