연구논문 Korean Journal of Optics and Photonics, Vol. 31, No. 1, February 2020, pp. 1-6 DOI: ISSN : (P

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1 연구논문 Korean Journal of Optics and Photonics, Vol. 31, No. 1, February 2020, pp. 1-6 DOI: ISSN : (Print) ISSN : X(Online) Polarization-sensitive Optical Coherence Tomography Imaging of Pleural Reaction Caused by Talc in an ex vivo Rabbit Model Jung-Eun Park 1*, Zhou Xin 2*, Chulho Oak 3*, Sungwon Kim 4, Haeyoung Lee 5, Eun-Kee Park 6, Minjung Jung 7, Daa Young Kwon 1, Shuo Tang 2, and Yeh-Chan Ahn 1 1 Department of Biomedical Engineering and Center for Marine-Integrated Biomedical Technology, Pukyong National University, 45, Yongso-ro, Nam-gu, Busan 48513, Korea 2 Department of Electrical and Computer Engineering, University of British Columbia, 2332 Main Mall, Vancouver V6T 1Z4, Canada 3 Department of Internal Medicine, Kosin University College of Medicine, 262, Gamcheon-ro, Seo-gu, Busan 49267, Korea 4 Department of Otolaryngology-Head and Neck Surgery, Kosin University College of Medicine, 262, Gamcheon-ro, Seo-gu, Busan 49267, Korea 5 Department of Thoracic and Cardiovascular Surgery, Kosin University College of Medicine, 262, Gamcheon-ro, Seo-gu, Busan 49267, Korea 6 Department of Medical Humanities and Social Medicine, Kosin University College of Medicine, 262, Gamcheon-ro, Seo-gu, Busan 49267, Korea 7 Department of Pathology, Kosin University College of Medicine, 262, Gamcheon-ro, Seo-gu, Busan 49267, Korea (Received December 9, 2019; Revised December 17, 2019; Accepted December 18, 2019) The chest wall, an organ directly affected by environmental particles through respiration, consists of ribs, a pleural layer and intercostal muscles. To diagnose early and treat disease in this body part, it is important to visualize the details of the chest wall, but the structure of the pleural layer cannot be seen by chest computed tomography or ultrasound. On the other hand, optical coherence tomography (OCT), with a high spatial resolution, is suited to observe pleural-layer response to talc, one of the fine materials. However, intensity-based OCT is weak in providing information to distinguish the detailed structure of the chest wall, and cannot distinguish the reaction of the pleural layer from the change in the muscle by the talc. Polarization-sensitive OCT (PS-OCT) takes advantage of the fact that specific tissues like muscle, which have optical birefringence, change the backscattered light s polarization state. Moreover, the birefringence of muscle associated with the arrangement of myofilaments indicates the muscle s condition, by measuring retardation change. The PS-OCT image is interpreted from three major perspectives for talc-exposure chest-wall imaging: a thickened pleural layer, a separation between pleural layer and muscle, and a phase-retardation measurement around lesions. In this paper, a rabbit chest wall after talc pleurodesis is investigated by PS-OCT. The PS-OCT images visualize the pleural layer and muscle, respectively, and this system shows different birefringence of normal and damaged lesions. Also, an analyisis based on phase-retardation slope supports results from the PS-OCT image and histology. Keywords: Polarization imaging, Optical coherence tomography, Phase retardation, Chest wall, Talc OCIS codes: ( ) Phase shift; ( ) Optical coherence tomography 생체외토끼모델에서의탈크에의해유발되는흉막반응의편광민감광결맞음단층촬영이미징 박정은 1* ㆍ Zhou Xin 2* ㆍ옥철호 3* ㆍ김성원 4 ㆍ이해영 5 ㆍ박은기 6 ㆍ정민정 7 ㆍ권다영 1 ㆍ Shuo Tang 2 ㆍ안예찬 1 1 부경대학교의생명기계전기융합공학협동과정우 부산광역시남구용소로 45 2 브리티시컬럼비아대학교전기컴퓨터공학과우 V6T 1Z4 캐나다밴쿠버메인몰 2332 *These authors contributed equally to this work. tang@ece.ubc.ca, ORCID: ahny@pknu.ac.kr, ORCID: Color versions of one or more of the figures in this paper are available online. 1

2 2 한국광학회지제 31 권제 1 호, 2020 년 2 월 3 고신대학교의과대학내과우 부산시서구감천로 고신대학교의과대학이비인후과우 부산시서구감천로 고신대학교의과대학흉부외과우 부산시서구감천로 고신대학교의과대학인문사회의학교실우 부산시서구감천로 고신대학교의과대학병리과우 부산시서구감천로 262 (2019 년 12 월 9 일받음, 2019 년 12 월 17 일수정본받음, 2019 년 12 월 18 일게재확정 ) 흉벽은호흡을통해환경입자의직접적인영향을받는기관으로늑골, 흉막층, 늑간근으로구성되어있다. 흉벽의질병을조기에진단하고치료하기위해서는흉벽의세세한부분을시각화하는것이중요하지만, 흉부전산화단층촬영이나초음파로는흉막층의구조를볼수없다. 반면, 고해상도의광결맞음단층촬영법 (optical coherence tomography, OCT) 은미세한재료중하나인탈크에의한흉막층의반응을관찰하는데적합하다. 그러나빛세기기반의광결맞음단층촬영법은흉벽의세부구조를구별할수있는정보를제공하기에는부족하여탈크에의한흉벽의반응과근육의변화를각각구별할수없다. 편광민감광결맞음단층촬영법 (polarization-sensitive OCT, PS-OCT) 은광학적복굴절을가진근육등의특정조직들이후방산란된빛의편광상태를변화시킨다는점을이용한다. 또한근필라멘트의배열과관련된근육의복굴절은지연변화를측정함으로써근육상태를나타낸다. 편광민감광결맞음단층촬영영상은두꺼운흉벽, 흉벽과근육간의분리, 병변주위의위상지연측정의세가지주요관점에서해석된다. 본논문에서는탈크흉막유착술 (pleurodesis) 을시행한토끼의흉벽을편광민감광결맞음단층촬영법으로연구하였다. 편광민감광결맞음단층촬영영상은각층과근육을시각화하였다. 그리고이시스템은정상과손상된병변의복굴절차이를보여주었다. 또한, 위상지연기울기기반분석을통해편광민감광결맞음단층촬영영상및조직학적결과를뒷받침하였다. Keywords: 편광이미징, 광결맞음단층촬영법, 위상지연, 흉벽, 탈크 OCIS codes: ( ) Phase shift; ( ) Optical coherence tomography I. 서론 체내의먼지, 석면같은다양한발암물질은단기적으로나장기적으로연구되어야하는중요한영역이다 [1]. 그러나흉막은매우얇은층이기때문에그러한종류의입자에노출된흉막내변화는염증과정의초기단계와악성흉막반응을구별하기어렵다. 게다가기존의이미징방법들은흉벽을검사하기에는한계가있기때문에흉막변화의이미징에관한연구는거의없었다. 예를들어, 초음파이미징은흉막과폐를구별하기에너무낮은이미지대조도를가진다 [2]. 그리고흉벽의두께에관한방사선학연구는사투영 (oblique projection) 에의해정상적인주변부밀도가더욱뚜렷해지면서흉막판 (pleural plaque) 으로식별될수있다는단점이있다 [3,4]. 또한, 양전자방출컴퓨터단층촬영 (positron emission tomographycomputed tomography, PET-CT) 을이용한연구는흉벽두께의뚜렷한변화를관찰할수없다 [5]. 반면에, 광결맞음단층촬영법을활용한연구는개발된흉부창 (window) 을통해수밀리미터깊이내에서뛰어난이미지해상도와대조도로두꺼운흉부영상을얻을수있다 [6]. 그러나정상조직과비정 상조직을직접구별하거나병변의경계를정의하는것의어려움은여전히남아있다 [7]. 광결맞음단층촬영법의기능적확장인편광민감광결맞음단층촬영법은조직에두개의편광을비추고각각의편광되어후방산란되는빛을감지한다 [8]. 복굴절특성을가진조직은빛이조직구조를통과하고반사하면서빛의편광상태를변화시키기때문에편광민감광결맞음단층촬영법은위상분석을이용함으로써기능적정보를제공할수있다. 의료영상분야의편광민감광결맞음단층촬영법연구를위해우리는교원섬유 (collagen fibers) 가풍부한피부, 각막, 힘줄, 연골등의조직과규칙적인섬유배열을하는골격근 ( 또는 A-밴드 ) 으로부터충분한샘플을찾을수있다 [9-14]. 한편, 탈크는흉막유착에가장광범위하게임상적으로사용되는물질이다. 환경오염물질인석면의흉막반응을설명하기위해대체재로사용되는물질이다. 본연구에서우리는그러한편광민감광결맞음단층촬영법의장점을이용하여탈크에의한흉막염증동물모델로근육의복굴절과그변화를가시화하였다. 또한, 복굴절의비교를통해근육층으로부터복굴절이없는흉벽을구별하였다.

3 연구논문 생체외토끼모델에서의탈크에의해유발되는흉막반응의 박정은ㆍ Zhou Xin 외 동물모델준비 II. 실험방법 동물실험은실험동물의관리및사용에대한가이드에기반하여수행되었다 [15]. 이실험은고신대학교의과대학동물연구위원회에의해승인받았다. 본연구에서우리는 3.0~3.5 kg의수컷뉴질랜드흰토끼를사용하였다. 첫번째근육내마취를위해케타민 5 mg/kg과자일라진 0.8 mg/kg을주입하였고, 마취깊이유지를위해케타민 10 mg/h과자일라진 3 mg/h을주입하였다. 실험내내산소포화도는귀맥박산소측정기로모니터되었다. 세마리의토끼는정상대조군 (n = 1) 과탈크실험군 (n = 2) 으로나뉘었다. 흉막유착술 (pleurodesis) 은이전의연구에따라수행되었다 [8]. 다시말해, 16게이지플라스틱카테터를통해오른쪽흉부공간에슬러리형태의탈크 (100 mg/kg) 가주입되었다. 통상인체에는 4~5 g/kg 사용되나소동물인토끼에는 100 mg/kg로선행논문에사용되었다. 실험에사용된동물들은흉막유착술 14일후에근육내케타민을주입한후 CO 2 가스에의해안락사시켰으며, 현미경검사, 광결맞음단층촬영법, 조직학적검사를통해분석되었다 편광민감광결맞음단층촬영시스템 편광민감광결맞음단층촬영법은존즈행렬 (Jones matrix) 을기반으로하여설계되었다 [8,16]. 이시스템의광원은중심파장이 1,060 nm, 반치전폭 (FWHM) 이 111 nm, 평균출력이 30 mw인미세전자기계시스템 (MEMS) 기반의파장가변광원 (swept source) 이었다. 광원의스캐닝속도는 100 khz, 스캐닝폭이 123 nm였다. 광섬유기반간섭계에서는두개의도브프리즘 (Dove prism) 이광경로차에의해직교하는두분극상태의결합을생성한다. 이시스템의사양은스캐닝부분에서측정된평균출력이 1.15 mw으로, 조직내에서깊이분해능은 6.2 µm였고 0.3~2.6 mm의깊이에서 db 의민감도와 db/mm의신호롤오프를가졌다. 각신호의측정된이미징범위는약 2.95 mm이다. 평균 ± 표준편차로나타내었다. 양측의 <0.10인 p값은통계적유의성을결정하였다 ( 케이스개수 n은각각정상 n = 4, 경도 n = 8, 중등도 n = 4) 편광민감광결맞음단층촬영법을이용한흉막두께측정연골에대한이전연구에도입되었던편광민감광결맞음단층촬영법을이용한위상지연분석의경우 [17], 수동으로선택한세지점에서위상지연을측정한후, 누적그래프를나타냈다. 정상조직에서는실험그룹들간의통계학적균형을맞추기위해세지점을지정하였고, 이는그림 1(c) 의편광민감광결맞음단층촬영이미지와그림 4(a) 의그래프에서 1, 2, 3으로표시하였다. 다른조직에서는그림 2에서그림 4까지볼수있듯이, 정상과유사한부분, 전이부분, 병변의세군데로지정하였으며, 이들은각각편광민감광결맞음단층촬영이미지와그래프에서 1, 2, 3의경우를나타낸다. 정상과유사한부위에서는편광민감광결맞음단층촬영영상에서근육층의균일한복굴절패턴이관찰되었다. 이부위는염증성삼출물로덮여있는흉막표면때문에정상조직과구별되었다. 병변은골격근밑에있는육아조직 (granulation tissue) 과석회화를가지고있었다. 전이부분은정상과유사한영역과병변사이의지점이었으며, 편광민감광결맞음단층촬영영상에서복굴절패턴의변화가관찰되었다. 기울기는 4개층내에서선형맞춤 (linear fitting) 으로구했다. 기울기를추정하기위해관심있는영역 ( 편광민감광결맞음단층촬영이미지의 1, 2, 3영역 ) 의각 A-라인은표면평탄화하고, 이웃한 10개의 A-라인 ( 왼쪽 5개와오른쪽 5개의 A-라인 ) 을평균을내어중간필터링을통해수정하였다 ( 케이스개수 n은각각정상 n = 33, 경도 n = 66, 중등도 n = 33). 서로다른특성을갖는분할영역을이전연구에서소개한 2.3. 병리학적검사및흉막두께측정 병리학적검사의경우, 흉막조직 ( 또는벽측흉막, 늑간근 ) 을 1 1 cm 2 조각으로잘라 10% 중성완충포르말린 (NBF) 에고정시키고파라핀에포매시켰다. 일련의섹션 (4 µm 두께 ) 을헤마톡실린 -에오신(H&E) 으로염색하고현미경으로검사를진행하였다. 병적인손상의정도 ( 중피층내손상 : 경도손상, 근육층을포함한손상 : 중등도손상 ) 에근거하여, 두마리의토끼로부터두개의경미한부상조직과한개의완화된부상조직을얻었다. 흉막의두께를측정하기위해각조직마다네군데측정지점을정점, 종격막, 횡격막을포함하여벽측흉막에서선택하였다. 병리학에서흉막반응의두께는중피층상부에서중피하층까지현미경적으로정의되었다. 통계분석은 SPSS 버전 17.0 (SPSS Inc., Chicago, IL, USA) 에의해수행되었다. 데이터는 Fig. 1. Normal pleural imaging. (a) Chest wall preparation after resection. The red line is the scanned area. (b) Cross-sectional image of intensity OCT. (c) Characteristic birefringence of healthy layers in PS-OCT. (d) Pathologic image showing thin mesothelium and healthy smooth muscle.

4 4 한국광학회지 제31권 제1호, 2020년 2월 방법에 따라 분석하였다[17]. 흉막의 이상을 구별하기 위해 각 케이스 별 복굴절 패턴을 정상 케이스와 비교하였고, 편광 민감 광 결맞음 단층 촬영법과 병리학에 의한 두께 결과 또 한 비교하였다. III. 실험 결과 및 토의 광 결맞음 단층촬영법으로 정상 흉막의 얇은 중피층과 인 접한 점막 하층을 포함한 표준 구조가 뚜렷하게 관찰되었다. 그러나 근육 층은 빛세기의 광 결맞음 단층촬영법으로는 관 찰이 어려웠다(그림 1(b)). 이러한 빛세기 기반의 광 결맞음 단층촬영 영상은 이전 연구를 뒷받침하였다[6,7]. 한편, 편광 민감 광 결맞음 단층촬영 영상은 서로 다른 복굴절 특성을 갖는 중피 층과 근육 층을 완전히 구별하였다(그림 1(c)). 그 리고 정상 조직의 조직학적 이미지는 얇은 흉막과 건강한 근 육도 보여주었다. 또한 탈크 그룹의 편광 민감 광 결맞음 단 층촬영 영상은 복굴절 패턴에 의해 층의 건강 상태를 보여주 었다(그림 2(c)와 3(c)). 영상에 따르면 정상 조직에서 관찰되 는 균일한 밴드 모양의 복굴절 패턴이 병변 내부와 주변에서 는 완전히 사라지거나 희미해졌다. 이러한 샘플들의 조직학 적 검사는 다양한 염증성 조직 변화를 보여준다. 이 분석은 중피 이상증식, 섬유아세포의 증식에 의한 흉막하 섬유 형성, 두꺼워진 교원섬유, 모세혈관의 수 증가 등의 유의한 과립화 반응(granulation reaction)을 보여주었다(그림 2(d), 3(d)). 즉 대조군과 거의 손상이 없는 샘플은 비교적 온전한 흉막 층과 근육 층을 가지고 있는 반면, 중등도 그룹의 민무늬근 은 염증세포와 섬유질로 침투되어 있었다. 그리고 흉막 층의 두께는 광 결맞음 단층촬영 영상과 편광 민감 광 결맞음 단 층촬영 영상에서 손상의 정도에 따라 상당히 증가하였다. 그림 4에서 볼 수 있듯이, 위상 지연의 기울기도 영상 결 Fig. 2. Imaging of pleura with a mild injury. The yellow arrows indicate the thickened pleura. (a) Chest wall preparation after resection. The red line is the scanned area. (b) Cross-sectional image of intensity OCT. (c) Thickened pleural layer and discontinued birefringence of layers in PS-OCT. 1 is a normal looking area, 2 is a transition area, and 3 is a lesion. (d) Pathologic examination showing thickened mesothelium and a stromal cell layer but intact muscle. Fig. 3. Imaging of a plural layer with a moderate injury. The yellow arrows indicate the thickened pleura. (a) Chest wall preparation after resection. The red line is the scanned area. (b) Cross-sectional image of intensity OCT. (c) Thickened pleural layer and discontinued birefringence of layers in PS-OCT. 1 is a normal looking area, 2 is a transition area, and 3 is a lesion. (d) Pathologic examination showing thickened mesothelium and a stromal cell layer with injured muscle. Fig. 4. Accumulated phase retardation curves along the depth, which does not consider the refractive index of each position as marking in the PS-OCT images and corresponding linear fits (LFs) (red dotted lines). (a) Normal case corresponding to Fig. 1. (b) Mild group corresponding to Fig. 2. (c) Moderate group corresponding to Fig. 3. Table 1. Pleural thickness according to tissue damage. Thickness was measured from PS-OCT and pathological images [µm] Normal Mild Moderate Histologic examination 48 ± ± ± 43.0 PS-OCT 46 ± ± ± 40.9

5 연구논문 생체외토끼모델에서의탈크에의해유발되는흉막반응의 박정은ㆍ Zhou Xin 외 5 과를뒷받침하며근육의손상단계를나타내었다. 기울기곡선의첫번째안정기 (plateau segment) 는흉막층의두께에해당된다. 다음세그먼트에서기울기 (gradient) 는정상으로보이는부위와병변에서의근육의복굴절상태를상대적으로나타낸다. 대조군에서는짧은첫번째안정기가얇은흉막층과일치했다 ( 그림 4(a)). 위상지연은깊이에따라큰변화를가졌고, 각기울기는측정위치에관계없이유사하였다. 따라서이분석결과는건강한조직의규칙적인근섬유배열과일치하였다. 그러나탈크모델그룹에서는위상지연대깊이비율이미미했다 ( 그림 4(b), 4(c)). 같은조직내의정상으로보이는부위와비교했을때도손상부위는위상지연기울기가더작았다. 구체적으로는각측정위치에서기울기를비교함으로써병변으로부터의거리가멀어짐에따라경사가증가하는것을확인하였다. 또한, 손상의정도가심할수록경사의차이는더욱컸다. 이때깊이방향으로접혀져 (wrapped) 있는형태인위상지연신호를 A라인을따라가며위상지연을단순누적함으로써위상펼침 (phase unwrapping) 을수행하였다. 표 1에따르면조직학적방법과편광민감광결맞음단층촬영법에의해측정된손상의정도에따른흉막의두께가서로일치했다. 비록편광민감광결맞음단층촬영법이이미징깊이의한계로인해근육내병변의크기를측정할수는없었지만, 흉막층두께의변화를측정한것은질병의진행정도를파악하는데의미가있다. IV. 결 석면같은미세입자들은호흡을통해서체내에들어오는경향이있다. 그러한입자들이체내로유입되면대부분은그대로남아몸전체에독소적영향을미친다. 따라서흉벽은탈크노출의직접적인영향을받기때문에먼저연구될필요성이있다. 더욱이흉벽의구조적변화는호흡기능과관련이있기때문에변화의정도를관찰하는것은그치료를함에있어중요한정보를제공할수있다. 빛세기기반의광결맞음단층촬영법을이용한흉벽과관련된이전연구에따르면, 흉막중피비후가확인되었으며흉막중피두께의영상분석결과는그것의조직학적결과와통계적으로일치하였다. 그러나광결맞음단층촬영시스템은손상된근육과병변경계의명확한경계를제공하지못했다. 본연구에서편광민감광결맞음단층촬영법은탈크노출후흉벽의두꺼워진중피와손상된근육의복굴절을연구하는데사용되었다. 건강한근육의동종 (homogeneous) 섬유구조는광학적비등방성에의한복굴절을보였고, 그림 1(c) 와그림 4(a) 에각각균일한복굴절패턴과가파른위상지연기울기를보였다. 영상으로부터근육은복굴절이없는흉막중피층과명확히구별되었다. 반면탈크에의해손상된 흉벽은염증또는발암으로인해근육내중피의비후와구 론 조적변화를가졌다. 편광민감광결맞음단층촬영법은이러한생리학적변화를관찰했다. 흉벽의표면에서육안으로식별하기에는병변이너무작지만편광민감광결맞음단층촬영영상은근육내병변의위치에서깨진복굴절패턴을확인하였다. 게다가기형근섬유를의미하는복굴절의변형된배열은손상의여지를결정하는단서가될수있는데, 이것은다른근육질환에대한근육의기능성을연구하거나수술의경계가중요할때더많이사용될수있다. 결과적으로, 편광민감광결맞음단층촬영법은복굴절및위상지연누적변화를제공함으로써병소의구조뿐만아니라다양한정보를파악하는데적합한도구가될수있다. 조직내의광특성을이용하여개별부위를구별하고, 병의정도를식별하며, 병변의치료목적으로병변의범위를결정하는데도움을줄수있다. 감사의글 이논문은 2015학년도부경대학교연구년 [II] 교수지원사업에의하여연구되었습니다 (C-D ). References 1. C. A. Pope III, R. T. Burnett, M. J. Thun, E. E. Calle, D. Krewski, K. Ito, and G. D. Thurston, Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution, Jama 287, (2002). 2. G. Volpicelli, Lung sonography, J. Ultrasound Med. 32, (2013). 3. C. Peacock, S. J. Copley, and D. M. Hansell, Asbestosrelated benign pleural disease: review, Clin. Radiol. 55, (2000). 4. T. C. McLoud, B. O. Woods, C. B. Carrington, G. R. Epler, and E. A. Gaensler, Diffuse pleural thickening in an asbestosexposed population: prevalence and causes, AJR Am. J. Roentgenol. 144, 9-18 (1985). 5. B. S. Kim, H. Kang, and J. G. Park, Pleural changes after talc pleurodesis in patients with underlying malignancy: comparison with recurrent malignant pleural lesions on CT and fluorodeoxyglucose-positron emission tomography/ct, J. Korean Soc. Radiol. 70, (2014). 6. Y.-C. Ahn, Y.-G. Chae, S. S. Hwang, B.-K. Chun, M. H. Jung, S. J. Nam, H.-Y. Lee, J. M. Chung, C. Oak, and E.-K. Park, In vivo optical coherence tomography imaging of the mesothelium using developed window models, J. Opt. Soc. Korea 19, (2015). 7. Y.-C. Ahn, C. Oak, J.-E. Park, M.-J. Jung, J.-H. Kim, H.-Y. Lee, S. W. Kim, E.-K. Park, and M. H. Jung, Ex vivo high-resolution optical coherence tomography (OCT) imaging of pleural reaction after pleurodesis using talc, J. Opt. Soc. Korea 20, (2016). 8. M. J. Ju, Y.-J. Hong, S. Makita, Y. Lim, K. Kurokawa,

6 6 한국광학회지제 31 권제 1 호, 2020 년 2 월 L. Duan, M. Miura, S. Tang, and Y. Yasuno, Advanced multi-contrast Jones matrix optical coherence tomography for Doppler and polarization sensitive imaging, Opt. Express 21, (2013). 9. M. C. Pierce, J. Strasswimmer, B. Hyle Park, B. Cense, and J. F. D. Boer, Birefringence measurements in human skin using polarization-sensitive optical coherence tomography, J. Biomed. Opt. 9, (2004). 10. M. C. Pierce, R. L. Sheridan, B. H. Park, B. Cense, and J. F. D. Boer, Collagen denaturation can be quantified in burned human skin using polarization-sensitive optical coherence tomography, Burns 30, (2004). 11. M. Pircher, C. K. Hitzenberger, and U. Schmidt-Erfurth, Polarization sensitive optical coherence tomography in the human eye, Prog. Retinal Eye Res. 30, (2011). 12. M. G. Ducros, J. D. Marsack, H. G. Rylander, S. L. Thomsen, and T. E. Milner, Primate retina imaging with polarizationsensitive optical coherence tomography, J. Opt. Soc. Am. A 18, (2001). 13. J. A. Burns, K. H. Kim, J. F. D. Boer, R. R. Anderson, and S. M. Zeitels, Polarization-sensitive optical coherence tomography imaging of benign and malignant laryngeal lesions: an in vivo study, Otolaryngol. Head. Neck. Surg. 145, (2011). 14. X. Yang, L. Chin, B. R. Klyen, T. Shavlakadze, R. A. McLaughlin, M. D. Grounds, and D. D. Sampson, Quantitative assessment of muscle damage in the mdx mouse model of Duchenne muscular dystrophy using polarization-sensitive optical coherence tomography, J. Appl. Physiol. 115, (2013). 15. National Research Council (US) Institute for Laboratory Animal Research, NIH Guide for the Care and Use of Laboratory Animals (National Academic Press, Washinton, US, 1996). 16. B. Baumann, W. Choi, B. Potsaid, D. Huang, J. S. Duker, and J. G. Fujimoto, Swept source / Fourier domain polarization sensitive optical coherence tomography with a passive polarization delay unit, Opt. Express 20, (2012). 17. V.-H. Le, S. Lee, B. Kim, Y. Yoon, C. J. Yoon, W. K. Chung, and K. H. Kim, Correlation between polarization sensitive optical coherence tomography and second harmonic generation microscopy in skin, Biomed. Opt. Express 6, (2015).

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