J Dent Hyg Sci Vol.13, No.2, 2013, pp.115-124 REVIEW ARTICLE Quantitative Light-Induced Fluorescence 의이해와치위생과정에서의활용방안 김희은 연세대학교치과대학예방치과학교실 Quantitative Light-Induced Fluorescence: A Potential Tool for Dental Hygiene Process Hee-Eun Kim Department of Preventive Dentistry & Public Oral Health, College of Dentistry, Yonsei University, Seoul 120-752, Korea Recently, there have been improvements in diagnostic methods for the assessment of early caries lesions. The reason is that dental professionals are seeking methods to reliably detect incipient dental caries and to remineralize them. This review examines the literature on principles, theoretical background, and history of the Quantitative Light-Induced Fluorescence (QLF) system (Inspektor Research Systems BV, The Netherlands). Furthermore, this paper discusses the potential application of QLF system to clinical practice for educational purpose, enabling dental hygiene students to perform oral health assessment using the QLF system. In addition, the clinical application of QLF system can motivate patients by providing additional visual information about caries and bacterial activity. The evidences on validity and reliability of the QLF system for detection of longitudinal changes in de/remineralization and caries were examined. The QLF system is capable of monitoring and quantifying mineral changes in early caries lesions. Therefore, it can be used to assess the impacts of caries preventive measures on the remineralization and reversal of the caries process. And the QLF system is a very promising equipment to assess educational effectiveness for dental hygiene students in their learning process. In conclusion, the QLF system is the most effective technology for more sensitive staging of caries and treatment without surgical intervention. Key Words: Dental caries, Dental hygiene process, Detection, Diagnosis, Quantitative light-induced fluorescence 서론 지난반세기동안전세계적으로치아우식증유병률은현저하게감소되었고 1,2), 우리나라역시 2012년국민구강건강실태조사에서 12세아동의치아우식증유병률이 1.84로조사되어이와비슷한추세를보이고있다. 이러한역학적변화로인해치과계는치아우식증의예방치료, 특히초기우식증의재광화치료에관심을가지게되었다. 이것은외과적치료법에근간을두었던치아우식증치료의패러다임이최근들어비외과적치료법으로옮겨지면서더욱큰화두가 되었다. 그러나이러한재광화치료가성공적으로수행되기위해서는무엇보다도초기우식증의정확한탐지 (detection) 및진단 (diagnosis) 이선행되어야한다 1,3-5). 초기우식증은치질에서무기질이소실된결과로치아표면이육안상주변의정상치질부분과구별되어하얗고불투명하게보인다 (Fig. 1A) 6). 초기우식증의조직학적특징을살펴보면, 병소부위는건전치면보다다공성이증가되어있긴하지만여전히무기질이풍부하게포함되어있어서우식병소본체에해당하는표면하방부위의무기질함량은약 10 70 vol% 정도이다 (Fig. 1B) 6). 이러한조직학적특 Received: June 12, 2013, Revised: June 14, 2013, Accepted: June 14, 2013 ISSN 1598-4478 (Print) / ISSN 2233-7679 (Online) Correspondence to: Hee-Eun Kim Department of Preventive Dentistry & Public Oral Health, College of Dentistry, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea Tel: +82-2-2228-3070, Fax: +82-2-392-2926, E-mail: 38317khe@yuhs.ac Copyright 2013 by the Korean Society of Dental Hygiene Science This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
J Dent Hyg Sci Vol. 13, No. 2, 2013 Fig. 1. Normal white light image (A) and histological image (B) of early caries lesion. 성때문에초기우식증을발생초기에탐지하기는매우어렵다. 전통적으로치아우식증은거의대부분치과의사의육안에의한시진 (visual inspection) 과탐침 (explorer) 을이용한촉진 (tactile assessment) 을통해진단되었으며, 보조적으로방사선사진촬영을병행하여치아우식증발병에대한임상적판단을내려왔다. 그러나이러한전통적인탐지방법은병소가법랑질외곽의최소 300 500 μm 정도깊이까지진행되었을때에만비로소탐지가가능하다고한다 7). 특히발생빈도가높은교합면의치아우식증은더욱초기단계에발견하기가힘들어서시진과촉진을함께병용할지라도실제교합면의치아우식증진단에대한민감도 (sensitivity) 는 20% 미만이고, 방사선검사시에도그민감도는 30% 에불과하여진단의정확성이매우떨어지는것으로보고되었다 8,9). 이러한진단상의한계점때문에치과병원마다치아우식증, 특히초기우식증에대한진단결과는매우큰차이를보여왔다. 이러한현상은진료계획에혼란을가중시킬뿐만아니라환자에게치과진료에대한불신을가중시키는경우도많았다. 또한초기우식증의경우, 병소를회복시킬수있는적절한치료시기를놓치고방치됨으로써와동이형성된후치아를재건하기위한수복치료를시작하게되는경우도상당수였다 2,10). 이러한전통적진단방법의한계점을극복하기위해서세계각지에서초기우식증에대한탐지장비의개발이매우활발하다. 가히춘추전국시대라고말할수있는초기우식증탐지장비의난립속에서도 Quantitative Light-Induced Fluorescence (QLF) 시스템 (Inspektor Research Systems BV, Amsterdam, The Netherlands) 은치아를구성하는무기질의미세한변화를민감하게탐지할수있기때문에, 초기우식증의발생여부및진행상태를평가하는데매우유용 한장비로인정받고있다 7,11-13). 따라서본연구에서는 QLF시스템의작동원리및진화과정을알아보고, 치위생과정수행시이것을어떻게활용할수있을지에대해제안하고자한다. 본론 1. QLF 시스템의원리및발전과정 1) 법랑질의자연형광 QLF 기술의가장핵심은자연치아의법랑질에서발생하는자가형광 (auto-fluorescence) 발현반응을수치로정량화하는것이다 14). 형광이란빛에너지를받은물질이이빛의자극에의해새로운빛을발산하는현상인데, 이때조사광보다형광의파장이길어지기때문에조사광과는다른색의빛을발산하게된다. 그동안치아에서발현되는형광은여러종류가보고되었다 15-17). 그중첫번째는근자외선영역에서여기 (excitation) 되는푸른색형광 (blue fluorescence) 이다. 두번째는푸른색과녹색계열의가시광선영역에서여기되는노란색 주황색 ( 녹색포함 ) 계열의형광 (yellow-orange fluorescence) 이고, 세번째는가장최근에밝혀진붉은색계열의형광 (red-infrared fluorescence) 이다. 이러한형광발현은그고유의색을띠게하는발색단 (chromophores) 이관여하는것으로보고되고있다. 첫번째푸른색형광은디티로신 (dityrosine) 이 18), 두번째노란색계열의형광은단백질구조내의가교결합사슬 (cross-linked chains) 이 19), 마지막으로붉은색형광은다양한프로토포피린 (protoporphyrines) 이치아조직에존재함으로써발현된다고한다 20,21). 116
김희은 :QLF 의이해와치위생과정에서의활용방안 QLF 시스템은최대강도 (peak intensity) 가 405 nm인푸른색가시광선을치아에조사한다 22). 이때건전한치아의법랑질조직은푸른색빛을흡수하고녹색 ( 노란색계열 ) 형광을발현하게된다. QLF 시스템은발현되는녹색형광을 좀더선명하게얻기위해서치아조직에서일부산란되는푸른색빛을제거하고자노란색특수필터 (λ>520 nm) 를구내카메라에장착하였고 (Fig. 2), 이것이바로 QLF의 1세대장비인 Inspektor Pro버전 (Inspektor Research Systems BV) 이다 (Fig. 3). Fig. 2. Quantitative Light-Induced Fluorescence concept: a blue excitation light beam with peak intensity at 405 nm illuminates a tooth, a yellow filter transmits green and red fluoresced photons to eye or camera. 2) QLF 시스템의초기우식증탐지원리 QLF 시스템이초기우식증을탐지하는원리를이해하기위해서는우선건전한치아조직과치아우식증부위에서색발현에차이가있음을알아야한다 (Table 1, 2). 특히, 가장주목할만한특징은법랑질병소부위에서빛의산란이증가하고녹색의자가형광발현이감소한다는것이다. QLF 시스템으로관찰시, 건전한치아의법랑질은녹색형광을발산한다. 그러나치아우식증이발생하는초기단계에서는무기질이소실된병소부위에이녹색형광의발현이줄어들어건전한부위와는구분되게상대적으로어둡게보인다 (Fig. 4). 선행연구들은여러가지기전으로형광소실의원인을설명하고있으나가장주된이유는다음과같다 12,23). 무기질이소실된병소부위는다공성이증가하게되 Fig. 3. Inspektor Pro system (A, B). (C) The Quantitative Light-Induced Fluorescence unit light box, demonstrating the handpiece and liquid light guide, (D) a close-up of the intra-oral camera featuring a disposable mirror tip that also acts as an ambient light shield (adapted from Pretty IA, J Dent 34: 727-739, 2006) 9). 117
J Dent Hyg Sci Vol. 13, No. 2, 2013 Table 1. Characteristics of the Elements Involved in Emitting Light on Enamel Health Transparency Translucent Oblique Light scattering Low High Light absorption Low Low Auto-fluorescence In blue and green part of spectrum, with minimum of red fluorescence Caries In blue and green part of spectrum lower than in healthy enamel, with elevation of exogenous red fluorescence Table 2. Characteristics of the Elements Involved in Emitting Light on Dentine Health Transparency Oblique Translucent Light scattering Low Lower Light absorption Low Low Auto-fluorescence In blue and green part of spectrum In blue and green part of spectrum higher than in healthy dentine red fluorescence from maillard products and exogenous red fluorescence Caries Fig. 4. White light image of a premolar with an approximal white spot (encircled area) on the left and its fluorescent image in the middle, which was green as visualized by the Inspektor Pro system on the right. 고, 따라서건전한부위에비해빛의산란현상이증가되면서형광발현의주된역할을하는법랑 상아질경계까지빛이도달되지못하게하는장벽이된다 (Fig. 5A). 또한치아조직내로흡수되는빛의양이감소하는것은물론이고형광이발생된다하더라도병소부위에의해재반사되기도하기때문에건전한부위에비해형광량이상대적으로줄어들게되는것이다 (Fig. 5B). 따라서 QLF 시스템에의해채득된치아이미지에서병소부위는 Fig. 4과같이상대적으로어둡게보이는것이다. 3) 탐지장비로서의 QLF 시스템의학문적근거 QLF 시스템은총 3가지종류의정량적인변수들 ( F, Area, Q) 을제시함으로써초기우식병소의상태를수치 Fig. 5. Green fluorescence shown schematically: blue photons enter the tooth and scatter in enamel and fluorescence green at the dentine (D) and enamel (E) junction (DEJ). Where there is a white spot (below in the enamel part) blue rays (A) scatter and will not reach the DEJ, fluoresced photons (B) will scatter back at the white spot, both effects resulting in a visual dark spot when viewed with Quantitative Light-Induced Fluorescence. 화하여판단할수있게한다. 첫번째로, F(%) 는병소부위의형광소실량 (fluorescence loss) 을나타내는데건전한부위에서발현되는녹색형광과비교했을때초기우식병소부위의줄어든형광량을상대적으로제시해주는변수이다. 두번째로, Area (mm 2 ) 는법랑질최외각부위에서측정된병소의면적을나타내는변수이고, 마지막으로, Q (% mm 2 ) 는 F와 Area의곱으로표현되는데, 결과적으로전체병소의부피를의미하게된다. 특히, 이세가지변수중에서 F(%) 는병소의깊이를대변할수있는데, 선 118
김희은 :QLF 의이해와치위생과정에서의활용방안 행연구에의하면 F는초기우식병소부위의병소깊이및무기질소실량을정량화하는 gold standard인 transverse microradiography과 0.62에서 0.88 사이의매우강한상관관계를가지는것으로보고됨으로써 F가병소의깊이를가늠할수있다는학문적근거를마련하였다 9,24-27). 한편, 병소부위는건전한부위와최소평균 5% 이상형광소실량의차이를보여야병소로분석된다 22). 이와더불어 QLF 시스템의초기우식증진단의정확성을판단하기위해병소의조직학적분석과비교한결과, 민감도는 0.77에서 0.93까지, 특이도 (specificity) 는 0.70에서 0.75까지보고됨으로써이탐지장비의초기우식병소에대한진단의타당성을확인할수있었다 9). 또한분석과정의신뢰도를조사해보았을때, 분석자간신뢰도는 0.93, 분석자내신뢰도는 0.92로파악되어 QLF 시스템을활용한초기우 식병소분석은매우일관되게진행될수있는것으로보고되었다 9). 또한 QLF 시스템은시진이나탐침, 혹은방사선사진검사와같은전통적인진단방법과견주어볼때, 초기우식병소를 2배이상잘탐지할수있다고보고되었다 7). 4) QLF 시스템의진화 QLF 시스템의개념은스웨덴의 Bjelkhagen과 Sundström 28) 에의해최초로제시되었다. 이들은 488 nm 파장을가진푸른색의아르곤레이저를치아에조사하면건전한치질과병소부위를구분할수있음을발견하였다. 이러한연구결과는치아우식증탐지분야에서매우획기적인결과이 Fig. 6. The concept of Quantitative Light-Induced Fluorescence Digital Biluminator 2. Fig. 7. Quantitative Light-Induced Fluorescence Digital Biluminator 2 (QLF-D) system (A) and light sources of the QLF-D (B). Fig. 8. Comparison with three kinds of light sources; normal white light (A), Inspektor Pro (B), and Quantitative Light-Induced Fluorescence Digital Biluminator 2 (C) images. 119
J Dent Hyg Sci Vol. 13, No. 2, 2013 긴하였으나빛의소스가레이저인이유로환자나술자에게가해지는위해 ( 危害 ) 의가능성이제기되었고, 이러한부분을수정보완한새로운장비가소개되었다 22). Inspektor Pro 는빛의소스를아르곤레이저대신 405 nm 파장의푸른색가시광선으로교체하였고, 핸드피스형태의구내카메라를광케이블로연결하여카메라에찍힌치아이미지를전용컴퓨터에전달할수있도록하였다 (Fig. 3C, 3D). 또한치아이미지를자동으로분석해주는소프트웨어프로그램을함께패키지화함으로써초기우식병소부위의무기질소실정도를정량화할수있도록하였다. 최근에는구강내이상증상의탐지에대한정확도를높이고, 임상활용의편의성을도모하기위해구내카메라대신디지털카메라를활용하여업그레이드시킨 QLF 시스템의 2세대버전인 Qantitative Light-Induced Fluorescence Digital Biluminator 2 (QLF-D) 가개발되었다 (Fig. 6, 7). QLF-D는탐지기능의정확도및이미지의질을높이기위해 4개의백색광원과 12개의푸른색광원의발광다이오드 (light-emitting diode) 가카메라에부착되었고 (Fig. 7B), 이로써 QLF-D는한번의촬영으로백색광의일반이미지 (Fig. 8A) 와 QLF-D의형광이미지 (Fig. 8C) 를연속적으로얻을수있게되었다. 또한 QLF-D는탐지의범위를넓혀서초기우식증뿐만아니라치면세균막이나치석등과같은박테리아관련산물들의탐지까지가능하도록하는특수필터를내장시켰다. 이와더불어이미지수집및관리를위한소프트웨어인 C3와이미지분석을위한소프트웨어인 QA2를함께제공함으로써환자의구강내이미지의질을높이고이를저장할수있으며, 환자구강상태의변화를좀더효율적으로비교분석할수있게하였다 (Fig. 9). 2. QLF 시스템의활용 QLF 시스템은초기우식병소의미세한무기질변화를정 확하게정량화할수있기때문에병소의진행상태를모니터링하기에매우유용한장비이다 (Fig. 10) 11). 보통임상에서시진이나방사선사진으로치아우식증을진단해낼수있으려면병소깊이가최소 300 500 μm까지침범되어야한 Fig. 10. Example of Quantitative Light-Induced Fluorescence (QLF) images. (A) White light image of early buccal caries effecting the maxillary teeth, (B) QLF image taken at the same time as (A), note the improved detection of lesions as a result of the increased contrast between sound and demineralised enamel, (C) 6 months after the institution of an oral hygiene programme, the lesions have resolved (adapted from Pretty IA, J Dent 34: 727-739, 2006) 9). Fig. 9. Quantitative Light-Induced Fluorescence Digital Biluminator 2 acquisition screen. 120
김희은 :QLF 의이해와치위생과정에서의활용방안 다 7). 우식병소가법랑질을관통하는데걸리는시간이평균 6년이라는선행연구를통해추론해보면 23,29,30), 초기우식병소부위에서탈회가시작된후적어도 1년 6개월에서 2년이상의시간이흘러야병소의탐지가가능해진다. 그런데우식병소가법랑질의 500 μm 이상을침범하고나면재광화치료로병소부위를회복시키기어렵다 7). 따라서무기질의변화에매우민감하게반응하는 QLF 시스템을치아우식증모니터링에활용하는것은초기우식증을좀더조기에발견하여재광화처치및관리를가능하게할수있음을시사한다. 불소함유치약의효능을평가하기위한선행연구에서 불소미함유치약과비교해서초기우식증에대한재광화의차이를단 3개월안에분명하게통계적으로구분해낸결과가이러한사실을뒷받침한다 31). 한편, 임상적경험이매우부족한학생들이치위생과정을수행할때치면세균막과치석및실란트나레진과같은수복물을건전한치면과구분하는것은쉽지않다. 그러나구강상태평가과정에 QLF 시스템을도입한다면학생들의임상적이해를도와교육의효과를배가시킬수있을것으로사료된다 (Fig. 11). 특히, 치위생과정수행의가장기본이되는치면세균막검사를시행할때사용하는치면착색제 Fig. 11. Example of Quantitative Light-Induced Fluorescence Digital Biluminator 2 (QLF-D) images with various cases, such as plaque (A, B), calculus (C, D), and resin filling (E, F). White light images (A, C, E) and QLF-D images (B, D, F) were taken at the same time. Fig. 12. Example of secondary caries. The Quantitative Light-Induced Fluorescence Digital Biluminator 2 (QLF-D) image (B) shows a lot of red fluorescence (RF) along the margins of the fillings. The left of the two central elements shows demineralization in combination with RF extending from the filling margin at the lower end of the surface. White light image (A) and QLF-D image (B) were taken at the same time. 121
J Dent Hyg Sci Vol. 13, No. 2, 2013 도포는과정상의번거로움과함께도포후구강주위의염색제착색으로인해술자와환자모두에게불편을야기할뿐만아니라적지않은시간이소모된다는단점이있었다. 그러나이때 QLF 시스템을활용하면치위생과정에서소요되는시간을절약할수있기때문에치위생과정수행의효율성을증대시킬수있을것이다. 또한 QLF 시스템을활용하면실란트대상치아선정시, 치아의건전한상태를정확히파악할수있다. 그리고실란트시술전소와나열구내에침적된치면세균막이완벽히제거되었는지도쉽게확인할수있고, 이미실란트치료가수행되었거나수복치료된치면의미세누출이나 2차우식증발생여부도쉽게확인이가능하다 (Fig. 12). 따라서실란트 Fig. 13. Calculus detection (A) and removal (B) by the Quantitative Light-Induced Fluorescence Digital Biluminator 2 system. White arrows indicate the same size. Fig. 14. Plaque visualization of orthodontic patient by the Quantitative Light-Induced Fluorescence Digital Biluminator 2 (QLF-D) system. White light image (A) and QLF-D image (B) were taken at the same time. 122
김희은 :QLF 의이해와치위생과정에서의활용방안 시술과정중 QLF 시스템을적극적으로활용한다면실란트성공률이현재보다훨씬더증가할것으로사료된다. 이와더불어예방목적의스케일링에대해보험적용이가능해지면서임상이나보건소에서이에대한수요가증가하고있기때문에 QLF 시스템을스케일링과정중에활용한다면환자의진료시간을효율적으로조절할수있을것으로사료된다 (Fig. 13). 또한교정장치를장착한환자의경우, 장치주변이나치아의인접면에서치아우식증이발생하게되면장치를제거할때까지적절한치료가지연되는경우가종종발생한다 (Fig. 14). 만약교정환자들을대상으로 QLF 시스템을적용한다면초기우식증을조기에탐지할수있기때문에교정치료를끝낸환자가치아우식증치료를이유로다시수복치료를하게되는안타까운상황을미연에방지할수있을것으로사료된다. 한편, 치위생관리를받는대상자들은본인의구강건강상태를사진으로직접확인할수있고동시에병소상태를정량화된수치로제공받을수있기때문에대상자자신의구강관리에대한동기부여에매우효과적일수있다. 특히, 재내원시마다변화되는구강상태를이전상태와비교하며시각적으로확인할수있는것은 QLF 시스템의매우큰장점으로써이러한기능을활용하여대상자에게구강관리의필요성을효율적으로부각시킬수있을것이라고사료된다. 결론 21세기로접어들면서 IT 분야의급성장과더불어진단의학분야는날이갈수록눈에띄게발전하고있다. 이러한흐름에힘입어보건의료계는 헬스케어 3.0 시대 를표방하며질병의예방과관리를강조한다. 치과계에서도구강상태를정확히탐지하고질병의진행상태를정량화시켜객관적으로제시해주는디지털탐지장비가출현함으로써구강질병을조기에진단하고예방및관리하는일련의과정이가능해졌다. 특히 QLF 시스템이국내에소개되면서구강내초기병소에대한신속ㆍ정확한치료계획수립이가능해졌고, 환자들의예방진료에대한순응도또한높아졌다. 특히, 치과임상뿐만아니라학교교육현장에서의활용도가높아지면서 QLF 시스템에대한관심은더욱고조되고있다. QLF 시스템은환자의구강상태에대해좀더객관적인근거자료를수집할수있도록함으로써임상적근거에기반한치위생과정수행이가능할것으로사료된다. 감사의글 본연구가나오기까지학문적조언과감수를아끼지않으신김백일교수님께진심으로감사드립니다. References 1. Marthaler TM: Changes in dental caries 1953-2003. Caries Res 38: 173-181, 2004. 2. Mejàre I, Stenlund H, Zelezny-Holmlund C: Caries incidence and lesion progression from adolescence to young adulthood: a prospective 15-year cohort study in Sweden. Caries Res 38: 130-141, 2004. 3. Chalmers JM: Minimal intervention dentistry: a new focus for dental hygiene. Dent Today 27: 132, 134, 136 passim, 2008. 4. Rao A, Malhotra N: The role of remineralizing agents in dentistry: a review. Compend Contin Educ Dent 32: 26-33, 2011. 5. Tranaeus S, Shi XQ, Angmar-Månsson B: Caries risk assessment: methods available to clinicians for caries detection. Community Dent Oral Epidemiol 33: 265-273, 2005. 6. Arends J, Christoffersen J: The nature of early caries lesions in enamel. J Dent Res 65: 2-11, 1986. 7. Stookey GK: Quantitative light fluorescence: a technology for early monitoring of the caries process. Dent Clin North Am 49: 753-770, vi, 2005. 8. Bader JD, Shugars DA, Bonito AJ: Systematic reviews of selected dental caries diagnostic and management methods. J Dent Educ 65: 960-968, 2001. 9. Pretty IA: Caries detection and diagnosis: novel technologies. J Dent 34: 727-739, 2006. 10. Ismail A: Diagnostic levels in dental public health planning. Caries Res 38: 199-203, 2004. 11. Ellwood RP, Goma J, Pretty IA: Caries clinical trial methods for the assessment of oral care products in the 21st century. Adv Dent Res 24: 32-35, 2012. 12. Angmar-Månsson B, ten Bosch JJ: Quantitative light-induced fluorescence (QLF): a method for assessment of incipient caries lesions. Dentomaxillofac Radiol 30: 298-307, 2001. 13. Heinrich-Weltzien R, Kühnisch J, van der Veen M, de Josselin de Jong E, Stösser L: Quantitative light-induced fluorescence (QLF TM )-A potential method for the dental practitioner. Quintessence Int 34:181-188, 2003. 14. Bjelkhagen H, Sundström F, Angmar-Månsson B, Rydén H: 123
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