使用三維追蹤倍頻顯微鏡系統診斷日光角化症

Abstract

日光角化症（AK）是一種常見的由太陽光引起的皮膚病變。它通常會導致皮膚角質細胞增殖病變。日光角化症的治療非常重要。因為它是浸入式鱗狀細胞皮膚癌（SCC）的癌前病變徵兆。而且，隨著年齡的增大，人們患上日光角化症的機率會越來越高。日光角化症患者通常會有多個病灶區域。為了日光角化症精確地診斷，本文提出了使用倍頻顯微鏡系統（HGM）作為成像研究工具。倍頻顯微鏡系統提供次微米級別的分辨率，這對於組織病理學檢查是至關重要的。而且倍頻顯微鏡對生物組織造成很小的光學損傷。通過比較倍頻顯微鏡和傳統切片的影像，本論文旨在尋找它們細胞形態學上的一致性，來說明倍頻顯微鏡影像從某種程度上可以代替傳統的切片影像進行診斷。5名年齡在70至93歲之間的日光角化症亞洲志願者（2名女性和3名男性）參與了這項研究。它含有1個離體樣品影像和4個活體影像。為了更好地進行臨床試驗，本文還發展了帶導光臂的可移動倍頻影像系統。在本文結果中，倍頻影像和傳統切片圖像均顯示角質層（SC）角化不全和角化過度現象。在棘層（SS）中，顯示不規則棘皮症，棘層結構異常，棘層細胞和細胞核的多形現象。在基底層（SB）中，均顯示基底細胞擁擠，細胞形態結構異常。在真皮中，倍頻影像還可以看出膠原蛋白組織日光彈性性變。此外，本文還說明了在倍頻圖像中發現的樹突狀結構細胞。本文的案例研究顯示，倍頻顯微影像有潛力成為日光角化症診斷的替代方案，也有助於醫師從事術後追蹤。

Actinic keratosis (AK) is a common cutaneous neoplasm consisting of proliferation of atypical epidermal keratinocytes resulting from severe solar damage. AKs are important because of their potential to develop into invasive cutaneous squamous cell carcinoma (SCC) with the highest incidence in the aged population. AK patients usually have multiple AKs. To study the diagnosis of AK, in vivo harmonic generation microscopy (HGM) was proposed as the imaging tool. HGM provides submicron resolution crucial for histopathological examination and causes little optical damage in bio-tissues. With HGM, this thesis is aimed at seeking out the consistent cell morphology in comparison with the H&E stained histopathological images. Five Asian volunteers (2 females and 3 males) aged from 70 to 93 years old with AK were enrolled in this study. It contained 1 ex vivo and 4 in vivo examinations. Due to the clinical demands, we also developed movable HGM system with light guide in this study. HGM and H&E images of AK both show parakeratosis and hyperkeratosis in the stratum corneum (SC), irregular acanthosis, abnormal architecture and pleomorphism of cells and nuclei in the stratum spinosum (SS), crowding of keratinocytes, abnormal architecture and pleomorphism of cells and nuclei in the stratum basale (SB), and solar elastosis in the dermis. Moreover, we also found dendritic-like cells in AK through HGM images. Our case study indicates that noninvasive HGM may become an alternative to invasive biopsy in the diagnosis of AKs and also helps physician to improve follow-up treatment assessment.