活體倍頻顯微術：皮膚內在老化於活性表皮與真皮乳突之定量分析

Quantitative Analysis of Intrinsic Skin Aging in Viable Epidermis and Dermal Papillae by In Vivo Harmonic Generation Microscopy

周信佑(Sin-Yo Chou)

指導教授 ： 孫啟光

國立臺灣大學/電機資訊學院/光電工程學研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.00467

摘要

皮膚的內在老化是一個由先天基因所決定且無法改變的自然過程。老化所造成的改變增加了皮膚的敏感性，也減弱了皮膚的防護功能，這樣的情況增加了老年人得到皮膚炎症(inflammation)及皮膚傳染疾病的發生率。為了揭露皮膚的內在老化，我們將一台波長為1230奈米的飛秒鉻：鎂橄欖石雷射作為光源，並將包含二倍頻及三倍頻訊號的非侵入式倍頻切片系統運用於取得高解析度的活體人體皮膚影像。我們一共取得了48名亞洲受試者的前臂內側皮膚的活體影像，受試者的膚色分類(Fitzpatrick skin phototype)皆為第三或第四類。我們從每位受試者的皮膚取得了間距相同的三維水平切面影像序列，影像的取得由角質層(stratum corneum)一直深入到上層網狀真皮層(reticular dermis)，而影像間距則被設定為2微米或5微米。利用三維水平切面影像序列，我們定義了14個參數，以三維的觀點來檢視活性表皮(viable epidermis)與真皮乳突(dermal papillae)的型態改變。
在活性表皮厚度的活體分析中，我們並未發現不包含網崤(rete ridge)的活性表
皮厚度與年齡或性別相關，而包含網崤的活性表皮厚度則隨著年齡增加而下降。分析結果暗示著真皮與表皮接合處(dermal-epidermal junction)在老化的皮膚中變得平坦。在孤立真皮乳突(isolated dermal papilla)的活體分析中，孤立真皮乳突高度和體積的平均、自身標準差與最大值皆隨著年齡增加而下降。其中只有孤立真皮乳突高度的平均與性別相關。此分析結果指出，內在老化造成了孤立真皮乳突的體型縮減，而在老化的皮膚中只剩下較小的孤立真皮乳突。在真皮乳突區域(dermal papilla zone)內的真皮乳突活體分析中，真皮乳突區域之厚度與三維叉合(interdigitation)指標皆隨著年齡增加而下降，而真皮乳突區域內真皮乳突體積比例則隨著年齡增加而上升。不過，真皮乳突數量密度、單位面積所含真皮乳突體積和真皮乳突平均體積則未發現與年齡之相關性。該分析的結果指出真皮與表皮接合處隨著年齡增加而變得平坦，但真皮乳突區域內真皮乳突的體積並未隨著年齡減少。隨著年齡增加，獨立的真皮乳突變得較快與其他乳突相連接，而在真皮乳突區域內整體的真皮乳突變得較寬。此外，三維叉合指標的分析顯示，真皮與表皮接合處的面積隨著老化而減少，這可能與老化皮膚的真皮與表皮黏附力減弱有關，並導致脆弱的老化皮膚。

關鍵字

倍頻顯微術 ； 活體成像 ； 內在老化 ； 活性表皮 ； 真皮乳突

並列摘要

Intrinsic aging of skin is a natural process genetically determined and inalterable. The aging-related changes increase the susceptibility of skin and reduced the skin barrier function, which increases incidence of inflammatory or infectious skin disorders in the elderly people. To reveal the changes of intrinsic skin aging, a 1230 nm femtosecond Cr:forsterite laser was used as the excitation, and the non-invasive harmonic generation biopsy (HGB) system collecting second-harmonic generation and third-harmonic generation signals was applied to acquire in vivo images with high spatial resolution from ventral forearms of 48 Asians with Fitzpatrick skin phototype III or IV. Using the HGB system, the XYZ image stacks of equally-spaced parallel horizontal sections were acquired with step size 2 μm or 5 μm beginning from the stratum corneum into the upper reticular dermis of the skin. Using XYZ image stacks, 14 parameters were defined to inspect morphological changes of viable epidermis and mainly dermal papillae in a three-dimensional point of view.
In the in vivo analysis of viable epidermis thickness, viable epidermis thickness excluding rete ridge was not found related to neither age nor gender, but viable epidermis thickness including rete ridge decreased with age. Results together implied that the dermal-epidermal junction flattened in the aged skin. In the in vivo analysis of isolated dermal papilla (IDP), the average, intra-subject SD, and maximum of IDP height and volume all decreased with age. Only the average of IDP height was found related to gender. The results indicated that intrinsic aging resulted in the shrinkage of the IDP in size, and there were only small IDPs remained in the elder skin. In the in vivo analysis of dermal papillae within dermal papilla zone (DPZ), both depth of DPZ and 3D interdigitation index decreased with age, but dermal papillae volume ratio within DPZ increased with age. However, number density of dermal papillae, dermal papillae volume per unit area, and average volume per dermal papillae were not found related to age. The results indicated that dermal-epidermal junction became flatter with age, but the dermal papillae within DPZ were not reduced in volume. The independent dermal papillae connected to each other quicker with age, and the whole dermal papillae within DPZ extended in width. Moreover, the analysis of 3D interdigitation index showed the decreasing interface area of dermal-epidermal junction with age, which might related to the fragility of the aged skin due to the weakening of epidermal-dermal adherence.

並列關鍵字

harmonic generation microscopy ； in vivo imaging ； intrinsic aging ； viable epidermis ； dermal papillae

參考文獻

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